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.

Pattern and Severity of Anaemia in Predialysis Chronic Kidney Disease Patients in Bangladesh: A Tertiary Care Hospital Study

Background: Anemia is a common complication in chronic kidney disease (CKD), and is associated with a reduced quality of life, and increased morbidity and mortality. The mechanisms involved in ananaemiassociated with CKD are diverse and complex. They include a decrease in endogenous erythropoietin (EPO) production, absolute and/or functional iron deficiency, and inflammation with increased hepcidin levels, among others. Objective: The objective of our study was to investigate the prevalence and severity of anaemia in pre-dialysis patients, and chronic kidney disease patients in Bangladesh.Material & Methods:This was a case-control prospective study conducted with over 300 Bangladeshi non-patients as the control group A and 87 with different stages of chronic kidney disease (CKD) patients as the case group B in the department of Nephrology BSMMU from April’2004 to June 2006. The normal people who had no history of diabetes mellitus, hypertension, or CKD and were not on any medication were controlled and different stages of the CKD patients who had no history of blood transfusion, erythropoietin and parental iron infusion were cases.Results:Out of 300 normal populations male was 158(52.7%) and the female was 142(47.3%) and the mean haemoglobin level of the male was 13.94 g/dl and the female was 12.29 g/dl. Among males 24(15.2%) and females 55(38.7%) were anaemic and the overall prevalence of anaemia was noted at 26.3%. Of the total anaemic people, 25% was microcytic anemia. Out of 87 CKD patients, 56 (64%) were male and 31 (36%) were female. The overall prevalence of anaemia in CKD patients was 95.4%. The haemoglobin level was <11g/dl in 57.14% patients with CCr 30-59 ml/min/1.73m2 which increases to 87.5 % in patients with CCr 15-29 ml/min/1.73m2, which also increases to 94.2 % in patients with CCr<15 ml/min/1.73m2. Mean haemoglobin was observed at 8.6 g/dl, 9.54 g/dl and 11.25 g/dl in stage V, stage IV and stage III CKD patients respectively. Anaemia appeared at 43.53 ml/min/1.73 m2 of CCR.Conclusions:The results demonstrate that patient with reduced renal function is more likely to have anaemia and the prevalence and severity of anaemia increase with declining kidney function. CCr and TSAT is the important predictor of anaemia. In a significant number of the CKD, patient anaemia was associated with iron deficiency.

Rescue of photoreceptor with human mesenchyme stem cell and human mesenchyme stem cell expressing erythropoietin in total degeneration of retina animal model

Purpose: This study aimed to investigate the efficacy of human?derived umbilical cord mesenchymal stem cells (HDUMSC) and human?derived umbilical cord mesenchymal stem cells expressing erythropoietin (HDUMSC?EPO) to rescue total degenerated retina in a rat model. Methods: The study included four treatment groups, namely negative control using normal saline (HBSS) injection, positive control using sodium iodide 60 mg/kg (SI), SI treated with HDUMSC, and SI treated with HDUMSC?EPO given via subretinal and intravenous routes, to test the efficacy of retinal regeneration following SI?induced retinal degeneration. Retinal function in both phases was tested via electroretinography (ERG) and histological staining examining the outer nuclear layer (ONL). Results: There was a statistically significant result (P < 0.05) in the SI treated with HDUMSC?EPO only when comparing day 11 (mean = 23.6 ?v), day 18 (mean = 25.2 ?v), day 26 (mean = 26.3 ?v), and day 32 (mean = 28.2 ?v) to the b?wave ERG on day 4 rescue injection day (mean = 12.5 ?v). The SI treated with HDUMSC?EPO showed significant improvement in b?wave ERG readings in the Sprague–Dawley (SD) rat but did not restore baseline readings prior to degeneration (day 0). Both treated groups’ ONL thicknesses did not show significant changes compared to the negative control group (HBSS) following rescue therapy. Conclusion: Total retinal degeneration following intravenous SI injection was observed at 60 mg/kg. SI treated with HDUMSC and HDUMSC?EPO showed no regenerative potential compared to baseline in SI?induced total retina degeneration on ERG or histology, whereas SI treated with HDUMSC?EPO group showed a substantial increase in b?wave ERG amplitude over time

Technical specification for clinical diagnosis and treatment of human parvovirus B19 infection in kidney transplant recipients (2022 edition) / 器官移植

Long-term use of immunosuppressant in kidney transplant recipients leads to poor immune function and infection with various pathogens. In recent years, along with the advancement of detection technique of human parvovirus B19 (HPV-B19) infection and the increasing quantity of kidney transplantation, the infection rate of HPV-B19 after kidney transplantation has been elevated year by year, becoming one of the major causes of pure red cell aplasia (PRCA), affecting the recovery of renal allograft function, and even leading to the injury or poor prognosis of renal allograft. To further standardize the diagnosis and treatment of HPV-B19 infection in kidney transplant recipients, Branch of Organ Transplantation of Chinese Medical Association and National Kidney Transplantation Quality Control Center jointly organized experts to formulate the clinical diagnosis and treatment specification for HPV-B19 infection after kidney transplantation from the perspectives of etiology, epidemiological characteristics, clinical manifestations, diagnosis, prevention, treatment, existing problems and prospects of HPV-B19, aiming to provide guidance for standardized prevention and treatment of HPV-B19 infection post-kidney transplantation in China.

Expression and significance of EPO and HIF-1α in serum and aqueous humor of patients with acute anterior uveitis / 国际眼科杂志(Guoji Yanke Zazhi)

@#AIM: To detect the expression of erythropoietin(EPO)and hypoxia-inducible factor-1α(HIF-1α)in serum and aqueous humor of patients with acute anterior uveitis(AAU), and to explore their clinical significance. <p>METHODS: From January 2018 to December 2020, 60 patients with AAU in our hospital were prospectively selected as the research objects, and 60 patients with proliferative vitreoretinopathy in the same period were taken as control(control group). The serum and aqueous humor of two groups were collected, enzyme-linked immunosorbent assay(ELISA)was used to detect the levels of EPO and HIF-1α in serum and aqueous humor; the self-rating anxiety scale(SAS)and the self-rating depression scale(SDS)were used to evaluate the AAU patients, and the severity of the disease was scored; Pearson method was used to analyze the correlation between SAS score, SDS score and levels of EPO and HIF-1α in serum and aqueous humor, and the correlation between levels of EPO and HIF-1α in the serum and aqueous humor. Spearman was used to analyze the correlation between the disease severity score of AAU patients and the levels of EPO and HIF-1α in serum and aqueous humor. <p>RESULTS: Compared with the control group, the levels of EPO and HIF-1α in the serum and aqueous humor of the study group were higher(<i>P</i><0.01). Among AAU patients, 23 were negative of SAS score and 37 were positive, and 29 were negative of SDS score and 31 were positive. Compared with patients with negative SAS score, the level of HIF-1α in serum and the level of EPO in the aqueous humor were higher in patients with positive SAS score(<i>P</i><0.05); compared with patients with negative SDS score, the level of EPO in serum and the levels of EPO and HIF-1α in aqueous humor were higher in patients with positive SDS score(<i>P</i><0.01). There were 26 mild patients and 34 severe patients with AAU. Compared with mild patients with AAU, the levels of EPO and HIF-1α in serum and aqueous humor were increased in severe patients(<i>P</i><0.01). Pearson analysis showed that the SAS and SDS scores of AAU patients were not significantly correlated with the levels of EPO and HIF-1α in serum and aqueous humor(<i>P</i>>0.05), there was a positive correlation between EPO and HIF-1α in serum(<i>P</i><0.05), and between EPO and HIF-1α in aqueous humor(<i>P</i><0.05). Spearman analysis showed that the disease severity score of AAU patients was positively correlated with the levels of EPO and HIF-1α in serum and aqueous humor(<i>P</i><0.05). <p>CONCLUSION: EPO and HIF-1α are highly expressed in serum and aqueous humor of AAU patients, and they are closely related. The two are closely related to the disease severity score, and should be paid attention to clinically.

Eritropoyetina (EPO) / Erythropoietin (EPO)

La eritropoyetina (EPO) es una hormona glucoproteica producida principalmente en las células peritubulares de los riñones, que regula la producción y diferenciación eritrocitaria. La síntesis de eritropoyetina está regulada por cambios en la disponibilidad del oxígeno, es decir, a mayor cantidad de oxígeno, menor producción de EPO, y a la inversa. La EPO se une a los receptores en las células madre hematopoyéticas CD34+, promoviendo la activación de los genes para estimular su proliferación y diferenciación hasta eritrocitos maduros [1]. La medición de eritropoyetina en suero es de gran utilidad para el diagnóstico de eritrocitosis y el establecimiento de su etiología. Su determinación en suero permite identificar si la producción eritrocitaria es autónoma (primaria), como en el caso de la producida en la policitemia vera, o secundaria, mediada por la eritropoyetina. En pacientes con eritrocitosis secundaria, los niveles de eritropoyetina están aumentados como un mecanismo compensatorio cuando es por hipoxia [2], o pueden ser el resultado de una patología que estimula su producción, como ocurre con ciertos tumores, entre otros factores. De acuerdo con la clasificación vigente de neoplasias hematolinfoides de la Organización Mundial de la Salud, los niveles disminuidos de eritropoyetina son un criterio menor para el diagnóstico de policitemia vera [2], y los niveles normales o elevados de eritropoyetina descartan que se trate de esta entidad e indican al médico tratante que debe explorar otras causas de eritrocitosis [2].

Prolonged response to recombinant human erythropoietin treatment in patients with myelodysplastic syndrome at a single referral centre in Brazil

OBJECTIVES: To evaluate the effects of epoetin (EPO) alfa treatment on overall survival, event-free survival and response duration in patients with myelodysplastic syndrome (MDS) who were treated at a haematological referral centre in northeastern Brazil. METHODS: This was a retrospective cohort study of 36 patients diagnosed with MDS and treated with EPO alfa at 30,000 to 60,000 IU per week. Clinical data were collected from medical records. The events assessed were non-response to treatment and progression to acute myeloid leukaemia (AML). Statistical analyses were performed using GraphPad Prism 7 and SPSS 24 software. RESULTS: The overall survival of patients who received EPO alfa treatment was 51.64%, with a median of 65 months of treatment, and the overall survival of this group was 100% during the first 24 months. We detected a 43.5-month median event-free survival, with a response rate of 80.5%. We observed responses from 25 to 175 months. Patients with transfusion dependence and those with a high-risk stratification, as determined by the International Prognostic Scoring System (IPSS), the Revised International Prognostic Scoring System (IPSS-R), the WHO classification-based Prognostic Scoring System (WPSS) and the WHO 2016, had a lower event-free survival than other patients. CONCLUSIONS: Despite the wide use of EPO alfa in the treatment of anaemia in patients with MDS, the median response duration is approximately only 24 months. Our data provide encouraging results concerning the benefits of using EPO alfa for the improvement of the quality of life, as patients treated with EPO showed higher overall survival, event-free survival rates and longer response durations than have been previously described in the literature.

Changes of EPO in rats with chronic renal failure and low immunity and reversal effects of Yougui Yin and exogenous EPO / 中国中药杂志

The aim of this paper was to observe the changes of EPO in rats with chronic renal failure and low immunity induced by adenine and to investigate the reversal effect of Yougui Yin(YGY)and exogenous EPO.SD rats were randomly divided into normal control group(n=20)and adenine-model group(n=90).The adenine-model group rats were given with adenine 150 mg·kg~(-1)for 14days by gavage administration,and then randomly divided into 8 groups as follows:model group(n=20),YGY groups(10,20,40 g·kg~(-1),10 in each group),rh EPO group(500,1 000,1 500 IU·kg~(-1),10 in each group),and Guilu Erxian Gao 10 g·kg~(-1)group(positive control group,n=10).From the 15th day,every group except normal control group received 150 mg·kg~(-1)adenine by gavage administration once every two days to maintain the model.Meanwhile,the rats in each YGY group and Guilu Erxian Gao group received corresponding drugs by gavage administration once a day for 30 days.The rats in rh EPO groups were subcutaneously injected with rh E-PO once every 3 days for 30 days.On day 46,rats were anesthetized to take blood and then sacrificed.The serum levels of creatinine,urea,glandular hormone,immunoglobulin,complement and interleukin,the proportion of T cells in the spleen,the killing rate of NKcells and the proliferative capacity of spleen cells were measured.Western blot was used to detect the key proteins in JAK2-STAT5 and NF-κB pathways mediated by EPO in kidney and spleen.As compared with the normal control group,the serum levels of CREA and UREA were increased significantly and the serum levels of ACTH,T and T3 were decreased significantly in the model group rats,indicating that the functions of kidney,adrenal gland,gonad and thyroid in rats were decreased.At the same time,the serum levels of Ig A,Ig G,Ig M,C3,C4,IL-2 and IL-6 were significantly decreased,the proportion of CD4~+,CD4~+/CD8~+T cell subsets,the killing rate of NK cell and the proliferation ability of spleen lymphocyte in spleen of the model group rats were significantly declined,indicating that the immune function of model group rats was decreased,and the model of kidney deficiency immunodeficiency was successfully constructed.As compared with the model group,both YGY and rh EPO significantly reduced serum levels of CREA and UREA,significantly increased serum levels of ACTH,T,T3,T4,Ig A,Ig G,Ig M,C3,C4,IL-2,and IL-6,increased the proportion of CD4~+,CD4~+/CD8~+T cell subsets,the killing rate of NK cell and the proliferation ability of spleen lymphocyte in spleen.YGY could significantly increase the content of EPO in serum.Both YGY and rh EPO could regulate the expression of EPOR,p-JAK2/JAK2,STAT5,NF-κB p50,NF-κB p65 and NF-κB IκB of EPO-mediated JAK2-STAT5 and NF-κB pathways in kidney and spleen.EPO is an important factor in the chronic renal failure and low immunity induced by adenine in rats.Exogenous EPO and YGY have significant reversal effects for the model rats.The mechanism of YGY may be related to the up-regulation of EPO in serum and regulating the expression of key proteins in EPO-mediated JAK2-STAT5 and NF-κB pathways in kidney and spleen.The mechanism of exogenous EPO may be related to regulating the expression of the key proteins in EPO-mediated JAK2-STAT5 and NF-κB pathways in kidney and spleen.

A 'extravagância' de trabalhar doente: o corpo no trabalho em indivíduos com diagnóstico de ler/dort / The 'extravagance' of working sick: the body work in individuals diagnosed with rsi/wrmd / La 'extravagancia' de trabajar enfermo: el cuerpo en el trabajo en individuos con diagnóstico de ler/epo

Resumo Dentre as doenças do trabalho mais prevalentes estão as lesões por esforços repetitivos/distúrbios osteomusculares relacionados ao trabalho, as quais relacionam-se diretamente à organização do trabalho que ignora os limites do corpo e as singularidades dos trabalhadores. O objetivo deste artigo foi investigar os significados do corpo no trabalho em indivíduos com esse tipo de lesão/distúrbio. Para alcançar o objetivo proposto, fez-se um estudo de caso com abordagem qualitativa, a qual está embasada na teoria sócio-histórica da psicologia. Utilizaram-se entrevistas abertas individuais para coleta de dados, realizadas com nove participantes, os quais tinham diagnóstico de lesões por esforços repetitivos/distúrbios osteomusculares relacionados ao trabalho e eram acompanhados no Centro de Referência em Saúde do Trabalhador de Botucatu (São Paulo). A análise dos dados revelou três núcleos de significação: necessidade de trabalhar — o corpo em movimento; submissão do corpo — falta de autonomia/poder; e corpo impedido — 'eu travei, eu parei minha vida'. Com base nesses núcleos foram identificados os significados e os elementos explicativos. O presenteísmo destacou-se entre os significados encontrados. A expressão que melhor define todo o processo saúde-doença dos participantes é 'a extravagância de trabalhar doente', e o produto deste é um futuro incerto.

Abstract Among the most prevalent occupational diseases are the Repetitive Strain Injury and Work-Related Musculoskeletal Disorders (RSI/WRMD), which are directly related to the organization of the work that ignores the limits of the body and the uniqueness of each worker. The study main focus was to investigate the significance of the body at work in individuals diagnosed with lesion/disturb. To achieve the proposed objective, a case study was held in a qualitative approach, which is based in the socio-historical theory of psychology. The means used to achieve the data was through individual open interviews with nine subjects whom had been diagnosed with RSI/WRMD and were accompanied at the Worker's Health Reference Center in Botucatu (São Paulo, Brazil). As a result, three meaning cores have been revealed: need to work - the 'body' in motion; body submission - lack of autonomy/power; and prevented body — 'I caught, I stopped in my life'. In addition to these, meanings and explanatory material have composed the illustrator scheme of results of this research. The phrase that best defines the whole process of health/disease measured in the interviews according to the scenario reported by the individuals is 'The extravagance of working sick', and the product of this, is an uncertain future.

Resumen Entre las enfermedades profesionales con mayor prevalencia se encuentran las lesiones por esfuerzos repetitivos/enfermedades profesionales osteomusculares (LER-EPO), las cuales se relacionan directamente con la organización del trabajo que ignora los límites del cuerpo y las particularidades de los trabajadores. El objetivo principal del estudio que dio origen a este artículo fue investigar los significados del cuerpo en el trabajo, en individuos con este tipo de lesión/enfermedad. Para alcanzar el objetivo propuesto, se realizó un estudio de caso con enfoque cualitativo, fundamentado en la teoría socio-histórica de la psicología. Se utilizaron entrevistas abiertas individuales para la recolección de datos, realizadas con nueve participantes, los cuales tenían diagnóstico de lesiones por esfuerzos repetitivos/enfermedades profesionales osteomusculares y tenían seguimiento del Centro de Referencia en Salud del Trabajador de Botucatu (São Paulo, Brasil). El análisis de los datos reveló tres núcleos de significación: necesidad de trabajar —el cuerpo en movimiento; sumisión del cuerpo —falta de autonomía/poder; y cuerpo impedido —'tuve un bloqueo, mi vida se detuvo'. En base a estos núcleos, se identificaron los significados y los elementos explicativos; El presentismo se destacó entre los significados encontrados. La expresión que mejor define todo el proceso salud-enfermedad de los participantes es 'la extravagancia de trabajar enfermo', y el producto de éste es un futuro incierto.

Therapeutic effect of L-carnitine combined with erythropoietin and iron on renal anemia in rats / 中国比较医学杂志

Objective To investigate the therapeutic effect of L-carnitine combined with erythropoietin (EPO) and iron on renal anemia in rats. Methods The renal anemia rat model was established using adenine. All rats were randomly divided into three groups: control group (group A), EPO combined with iron group (group B), and L-carnitine combined with EPO and iron treatment group (group C). The levels of red blood cells (RBC), hemoglobin (Hgb), hematocrit (Hct), C-reactive protein (CRP), Fe in peripheral blood (Fe), serum ferritin (SF) and transferrin saturation (TS) were measured. Pathological changes in the kidney, liver and small intestine tissues were examined using HE staining. Results Compared with the group A, the levels of RBC, Hgb, Hct, Fe, SF, and TS were significantly increased, however, the level of CRP significantly decreased in the groups B and C (P＜ 0. 05). In the group C, the levels of RBC, Hgb, and CRP was higher than the group B (P＜ 0. 05). Furthermore, the pathological changes in the kidney, liver and small intestine tissues were improved in the groups B and C. Conclusions L-carnitine combined with EPO and iron has a therapeutic effect on renal anemia in rats, thus, it deserves further studies and application.

Neuroprotective effect of erythropoietin on rat model of hypoxic-ischemic encephalopathy / 中国比较医学杂志

Objective To study the protective effect of recombinant human erythropoietin (EPO) on brain and to explore the changes in the diversity of intestinal microbial flora in neonatal rats with hypoxic-ischemic encephalopathy (HIE) by establishing a neonatal rat model of HIE, and to provide an experimental basis for clinical application of EPO in the treatment of neonatal HIE. Methods The HIE model was established in 7-day-old neonatal SD rats. The rats were randomly divided into the HIE model group, EPO-treated group and control group. The changes of nestin expression were detected by immunohistochemistry. Feces of the rats were collected to detect the changes in intestinal microbial flora by 16s rRNA sequencing. Results The expressions of nestin at the same time point in each group were significantly different (P ＜0. 05). The nestin level in the control group was the lowest, that in the EPO-treated group was the highest, and the HIE model group in between. The Shannon-Wiener index of the HIE model group showed a tendency to decrease compared with the control group. Conclusions Exogenous EPO can promote the growth of neural cells in neonatal rats with HIE, indicating a certain protective effect. Meanwhile, the diversity of intestinal microbial flora of the HIE neonatal rats is also changed.

Preliminary study of the effect of EPO pretreatment of bone marrow mesenchymal stem cells on preventing acute rejection after renal transplantation in rats / 器官移植

Objective To investigate the role of bone marrow mesenchymal stem cells (BMSCs) pretreated with erythropoietin (EPO) in the prevention of acute rejection after renal transplantation in rats. Methods BMSCs were divided into five groups: control group (without EPO), group A (pretreated with EPO at a final concentration of 10 IU/mL), group B (pretreated with EPO at a final concentration of 100 IU/mL), group C (pretreated with EPO at a final concentration of 500 IU/mL) and group D (pretreated with EPO at a final concentration of 1 000 IU/mL). In each group, the BMSCs were cultured for 24 h and 48 h. The proliferation rate of the BMSCs was determined by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay. The BMSCs were divided into two groups: BMSC group (without EPO) and EPO-BMSC group (pretreated with EPO at a final concentration of 500 IU/mL). After 48 h culture, Western blot was adopted to measure the expression level of CXC chemokine receptor (CXCR) 4 protein in BMSCs. Wistar rats were used as the donors, and SD rats were utilized as the recipients to establish the rat models with acute rejection after renal transplantation. The recipient rats were randomly divided into four groups (n=6 in each group) including the control group (without any intervention), EPO group (injection of 1 mL of solution containing 500 IU EPO via tail vein immediately after surgery), BMSC group (injection of 1 mL of solution containing 1×106/mL BMSCs via tail vein immediately after surgery) and EPO-BMSC group (injection of 1 mL of solution containing 1×106/mL BMSCs cultured in vitro with 500 IU/mL EPO via tail vein). The level of serum creatinine (Scr) level was determined by Scr detection kit. Western blot was used to detect the expression levels of interferon (IFN)-γ and interleukin (IL)-4 proteins. Results After 24 h culture, the proliferation rate of BMSCs did not significantly differ among all groups (all P>0.05). After 48 h culture, the proliferation rate of BMSCs in group C (pretreated with EPO at a final concentration of 500 IU/mL) was significantly higher than that in the control group (P<0.05). Compared with the BMSC group, the expression level of CXCR4 protein on the surface of BMSCs was higher in the EPO-BMSC group (P<0.05). At 1 d after renal transplantation, the levels of Scr did not significantly differ among all groups (all P>0.05). At 5 d after operation, the levels of Scr in the EPO, BMSC and EPO-BMSC groups were significantly lower than that in the control group (all P<0.05). The level of Scr in the EPO-BMSC group was markedly lower than those in the EPO and BMSC groups (both P<0.05). At postoperative 1 d and 5 d, the expression levels of IL-4 protein in the kidney tissues did not significantly differ among all groups (all P>0.05). At 1 d after surgery, compared with control group, the expression levels of IFN-γ protein and IFN-γ/IL-4 ratio in the renal tissues in the EPO, BMSC and EPO-BMSC groups were significantly decreased to varying extents (all P<0.05), and similar results were obtained at 5 d after surgery (all P<0.05). The expression levels of IFN-γ protein and IFN-γ/IL-4 ratio in the EPO-BMSC group were significantly lower than those in the EPO group and BMSC group (both P<0.05). Conclusions BMSCs pretreated with EPO can prevent the incidence of acute rejection after renal transplantation and protect the renal graft function.

The erythropoietin expression in hippocampus of rats with delayed encephalopathy after acute carbon mon-oxide poisoning / 实用医学杂志

Objective To observe the effect of erythropoietin(EPO)in rats with delayed encephalopathy after acute carbon monoxide poisoning (DEACMP). Methods A total of 90 male adult SD rats were randomly divided into three groups:blank control group(BC group),air control group(AC group)and DEACMP group. Time points(1,3,7,14,21 and 28 days after acute carbon monoxide poisoning)were set for measuring the changes. Pure CO were injected into the abdominal cavity of the rats from DEACMP group for several times to estab-lish DEACMP model. Rats in AC group were injected with equal volume of air by the same way. BC group were without any treatment. Morris water maze test was used to measure the cognitive behavior. The apoptosis of pyrami-dal neurons at hippocampus was measured by TUNEL. The expression of erythropoietin(EPO)in hippocampus was measured by immunohistochemistry. Results The average escaped latency of rats in DEACMP group increased after poisoning compared with rats in other two groups(P<0.05). The apoptosis of pyramidal neurons in hippocam-pus increased from day 1 after the CO poisoning. It reached the peak at day 7 and it still had a high expression at day 28. The apoptotic index in DEACMP group increased significantly compare with that of BC group and AC group (P < 0.05). The expression of EPO in hippocampus was found increased from day 1 after the CO poisoning and reached the peak at day 3. It began to reduce at day 7. The expression in DEACMP group was higher than those of other two groups (P < 0.05). Conclusions It may be one of the causes of the DEACMP that the expression of EPO decreased in the middle and late stage after CO poisoning and its anti-apoptosis was decreased.

The erythropoietin expression in hippocampus of rats with delayed encephalopathy after acute carbon mon-oxide poisoning / 实用医学杂志

Objective To observe the effect of erythropoietin(EPO)in rats with delayed encephalopathy after acute carbon monoxide poisoning (DEACMP). Methods A total of 90 male adult SD rats were randomly divided into three groups:blank control group(BC group),air control group(AC group)and DEACMP group. Time points(1,3,7,14,21 and 28 days after acute carbon monoxide poisoning)were set for measuring the changes. Pure CO were injected into the abdominal cavity of the rats from DEACMP group for several times to estab-lish DEACMP model. Rats in AC group were injected with equal volume of air by the same way. BC group were without any treatment. Morris water maze test was used to measure the cognitive behavior. The apoptosis of pyrami-dal neurons at hippocampus was measured by TUNEL. The expression of erythropoietin(EPO)in hippocampus was measured by immunohistochemistry. Results The average escaped latency of rats in DEACMP group increased after poisoning compared with rats in other two groups(P<0.05). The apoptosis of pyramidal neurons in hippocam-pus increased from day 1 after the CO poisoning. It reached the peak at day 7 and it still had a high expression at day 28. The apoptotic index in DEACMP group increased significantly compare with that of BC group and AC group (P < 0.05). The expression of EPO in hippocampus was found increased from day 1 after the CO poisoning and reached the peak at day 3. It began to reduce at day 7. The expression in DEACMP group was higher than those of other two groups (P < 0.05). Conclusions It may be one of the causes of the DEACMP that the expression of EPO decreased in the middle and late stage after CO poisoning and its anti-apoptosis was decreased.

Expression and Clinical Significance of Serum Levels of IL-12, IFN-γ,EPO and Ferritin in Patients with Acute Leukemia / 现代生物医学进展

Objective:To study the expressions of serum levels of intedeukin-12 (IL-12),interferon-γ (IFN-γ),erythropoietin (EPO) and ferritin in patients with acute leukemia and its clinical significance.Methods:76 patients with acute leukemia who were treated in our hospital from July 2015 to July 2016 were selected as the observation group,including 31 cases of newly diagnosed group,25 cases of remission group and 20 cases of relapse group.And another 76 cases who had taken the physical examination in our hospital were selected as the control group.Then the levels of serum IL-12,IFN-γ,EPO and ferritin in patients were observed and compared between the two groups.Results:The levels of IL-12 and IFN-γ in the observation group were significantly lower than those of the control group,and the levels of EPO and ferritin were significantly higher than those of the control group (P ＜0.05).The levels of serum IL-12 and IFN-γ in the untreated group and the relapse group were significantly lower than those of the remission group [(84.21± 5.43)pg/mL,(98.7± 7.98)pg/mL VS(112.43± 10.21) pg/mL,(38.54± 3.56)pg/mL,(49.87± 4.02)pg/mL VS(108.32± 8.43)pg/mL](P ＜0.05),and the levels of EPO and ferritin were significantly higher than those of the remission group [(402.32± 42.31) mIU/mL (321.58± 30.21)mIU/mL VS (98.21 ± 9.45) mIU/mLM (653.21 ± 54.24) ng/mLM (512.87 ± 43.45)ng/mL VS (342.15 ± 25.12)ng/mL] (P＜0.05).Conclusion:The serum levels of IL-12 and IFN-γ in patients with acute leukemia were lower,and the expression of EPO and ferritin was higher,and the disease and prognosis could be evaluated by monitoring the changes of these indexes.

An international collaborative research to evaluate the reference substance of anti-human EPO monoclonal antibody / 中国药学杂志

OBJECTIVE: To assess a panel of 9 human monoclonal antibodies against human erythropoietin (EPO) with defined characteristics (non-neutralizing, neutralizing, affinities) for suitability for EPO antibody assays. METHODS: A multi-center collaborative study involving three different laboratories and different assay platforms was carried out. Direct ELISA was used to test the affinities of the samples by Shenyang Sunshine pharmaceutical Co., Ltd and National Institutes for Food and Drug control, while indirect ELISA was used by Xiamen amoytop biotech Co., Ltd. The neutralizing assays were performed using UT-7 cell line by all the three laboratories. RESULTS: The properties of the 9 human monoclonal antibodies against human erythropoietin were assessed efficiently by all the three laboratories using different METHODS. CONCLUSION: It is suggested that the EPO antibody panel is established to enable the evaluation of the performance of different EPO antibody assays and thus the selection of appropriate assay for clinical use.

Effect of Xiaoyan Decoction on bone marrow suppression of mice with Lewis lung cancer / 中草药

Objective: To study the effects and mechanism of Xiaoyan Decoction on bone marrow suppression in mice from aspects of peripheral blood cell ratio, immune function, and cytokines. Methods: A mouse model of bone marrow suppression was established. Fifty mice were randomly divided into five groups (n = 10): control group, model group, Xiaoyan Decoction group, rhG-CSF group, and Xiaoyan Decoction combined with rhG-CS group. Lewis-tumor mice in Xiaoyan Decoction group were ig given Xiaoyan Decoction 18.2 g/(kg·d) twice daily, for 7 d. Lewis-tumor mice in rhG-CS group were treated by sc injection of rhG-CSF. The routine blood test, immunological functions of peripheral blood and cytokines (IL-3, IL-6, EPO, and GM-CSF) in serum were detected. Results: The bone marrow suppression model was successfully established. Compared with control group, the levels of WBC, RBC, Hb, and PLT in peripheral blood of model group were decreased, especially in WBC (P 0.05). The concentration of IL-3 and IL-6 was dramatically reduced in model group compared with control group (P < 0.05). And it showed an obviously increasing trend in IL-3, IL-6, EPO, and GM-CSF levels in Xiaoyan Decoction group and combined group, as well as an increase in IL-3, IL-6 levels in rhG-CS group (P < 0.05). Conclusion: It shows that Xiaoyan Decoction combined with rhG-CS can improve the level of WBC and immunological functions of peripheral blood in bone marrow suppression model mice. And the effect of combination of both drugs is more significant. This might be related to the effect of promoting the production of serum hematopoietic regulator such as IL-3, IL-6, EPO, and GM-CSF, and relieving chemotherapy-induced bone marrow suppression.

Erythropoietin-β in chronical kidney diseases children non-responsive to EPO-α: A case report and review of the literature / 中国药学杂志

OBJECTIVE: To report a clinical case and review the therapy of renal anemia in children with EPO-α non-response to provide ideas on optimization of dosing regimens and new ways of clinical practice. METHODS: One case of renal anemia was described and analyzed, and relevant literature was accessed and reviewed. RESULTS: The level of hemoglobin increased to 100 g·L-1 and the clinical symptoms were alleviated after transfering to EPO-β from EPO-α. CONCLUSION: For pediatric patients with chronic renal anemia, EPO-β instead of EPO-α is effective.

Expression of caspase-3 and transposition of Omi/HtrA2 in H9C2 by erythropoietin and/or Omi/HtrA2 silencing / 西安交通大学学报(医学版)

Objective To observe the expression of caspase-3 and transposition of Omi/HtrA2 in H9C2 by erythropoietin and/or Omi/HtrA2 silencing to explore the related anti-apoptotic mechanisms.Methods The cultured H9C2 cardiomyocytes were divided into control group,H/R group (anoxia 2 h and re-oxygenation 24 h), and different concentrations of EPO treatment groups.The release rate of lactate dehydrogenase (LDH)in cell supernatant was measured in each group.Expressions of cleaved caspase-3 and Omi/HtrA2 were measured by Western blot;then the transposition of Omi/HtrA2 between cytoplasm and mitochondria was observed.Specific siRNA interfering fragment was transfected into H9C2 cardiomyocytes by liposome method.Its silencing effect on Omi/HtrA2 was measured by RT-PCR and Western blot.The survival rate,release rate and expression of cleaved caspase-3 were measured.And the expression of Omi/HtrA2 was measured in cytoplasm and mitochondria in H9C2 (transposition of Omi/HtrA2 ).Results Compared with H/R group,the release of LDH and expression of cleaved caspase-3 were decreased; the transposition of Omi/HtrA2 from mitochondria to cytoplasm in H/R treatment groups was increased compared with control group,while that in EPO (20 IU/mL)group decreased.si-HtrA2 group transfected with siRNA showed a decreased release of LDH and expression of cleaved caspase-3 with all significant variances (P <0.05).Conclusion EPO exerts a cytoprotective effect by inhibiting the transposition of Omi/HtrA2 and hence the activation of caspases-3 pathway.

Effects of EPO on expression of TGF-β1 and ColⅠin myocardium of liver cirrhosis rats / 中国药理学通报

Aim To observe the effects of liver cirrho-sis on the expression of transforming growth factor-β1 ( TGF-β1 ) and ColⅠin rat myocardium and interven-tion of erythropoietin ( EPO ) . Methods Thirty-six male Sprague-Dasley rats were randomly divided into three groups:control group, liver cirrhosis group and EPO group, then the cardic hemodynamic parameters in vivo and levels of serum lactate dehydrogenase ( LDH ) as well as creatine kinase isoenzyme ( CK-MB) were measured. With Masson′s trichrome stain, changes of collagen formation of myocardial tissue in different groups were observed. Also the mRNA ex-pressions of TGF-β1 and ColⅠin myocardium were de-tected by RT-PCR. Results In contrast to control group, rats in liver cirrhosis group showed a decline in systolic and diastolic function of left ventricule, rising myocardial enzyme, a distinct increase of cardiac colla-gen deposition, as well as an elevation of TGF-β1 and ColⅠmRNA expressions. In contrast to liver cirrhosis group, rats in EPO group demonstrated an improve-ment in systolic and diastolic function of left ventricule as well as in cardiac collagen deposition, and a de-crease in both myocardial enzyme and TGF-β1 and ColⅠmRNA expressions. Conclusion Liver cirrhosis can lead to the changes of myocardial structure and function in rats,and it can accelerate myocardial inter-stitial fibrosis; EPO can protect the myocardial injury in liver cirrhosis rats.