Clinical Observation on Treatment of Chronic Aplastic Anemia by Shengxuening (生血宁) and Cyclosporin A

Objective： To explore the therapy to further elevate the efficacy of the treatment of chronic aplastic anemia （CAA）. Methods： Forty-five patients with CCA were assigned into two groups, the 26 patients in the treated group were treated by Shengxuening （ 生血宁, a Chinese herbal preparation） and cyclosporin A （CsA）, and the 19 patients in the control group were treated with androgen alone, with the therapeutic course lasting for over 3 months. Changes of peripheral blood picture, and the colony productivity of burst forming unit-erythroid （BFU-E）, colony forming unit-erythroid （CFU-E） and colony forming unit-granulocyte macrophage （CFU-GM） in bone marrow were observed before and after 3 months treatment. The amount of erythrocyte and platelet infusion, frequency of infection, condition of hemorrhage and relevant death were also observed. The follow-up study was conducted for over half a year. Results： The total effective rate in the treated group was 84.6 %, which was significantly higher than that in the control group （52.6 %, P〈0.05）. Levels of hemoglobin, reticulocyte, neutrophil and platelet increased after treatment in the treated group, as compared with those before treatment, with significant difference （ P〈0.05）, and the colony productivity of BFU-E, CFU-E and CFU-GM in bone marrow also got significantly increased （ P〈0.01 ）, and showed significant difference from those in the control group （P〈0.05）. Conclusion： Shengxuening-assisting CsA therapy is an effective measure for treatment of CAA.

Aplastic anemia and severe pancytopenia during treatment with peg-interferon,ribavirin and telaprevir for chronic hepatitis C

Telaprevir and Boceprevir are the first direct acting antivirals approved for chronic hepatitis C in combination with peg-interferon alfa and ribavirin.Pancytopenia due to myelotoxicity caused by these drugs may occur,but severe hematological abnormalities or aplastic anemia(AA) have not been described.We collected all cases of severe pancytopenia observed during triple therapy with telaprevir in four Spanish centers since approval of the drug in 2011.Among 142 cirrhotic patients receiving treatment,7 cases of severe pancytopenia(5%) were identified and three were consistent with the diagnosis of AA.Mean age was 59 years,five patients had compensated cirrhosis and two patients had severe hepatitis C recurrence after liver transplantation.Severe pancytopenia was diagnosed a median of 10 wk after the initiation of therapy.Three patients had pre-treatment hematological abnormalities related to splenomegaly.In six patients,antiviral treatment was interrupted at the onset of hematological abnormalities.Two patients died due to septic complications and one patient due to acute alveolar hemorrhage.The remaining patients recovered.Severe pancytopenia and especially AA,are not rare during triple therapy with telaprevir in patients with advanced liver disease.Close monitoring is imperative in this setting to promptly detect serious hematological disorders and to prevent further complications.

Effect of ginsenoside Rg1 on hematopoietic stem cells in treating aplastic anemia in mice via MAPK pathway

BACKGROUND Aplastic anemia(AA)presents a significant clinical challenge as a life-threatening condition due to failure to produce essential blood cells,with the current the-rapeutic options being notably limited.AIM To assess the therapeutic potential of ginsenoside Rg1 on AA,specifically its protective effects,while elucidating the mechanism at play.METHODS We employed a model of myelosuppression induced by cyclophosphamide(CTX)in C57 mice,followed by administration of ginsenoside Rg1 over 13 d.The invest-igation included examining the bone marrow,thymus and spleen for pathological changes via hematoxylin-eosin staining.Moreover,orbital blood of mice was collected for blood routine examinations.Flow cytometry was employed to identify the impact of ginsenoside Rg1 on cell apoptosis and cycle in the bone marrow of AA mice.Additionally,the study further evaluated cytokine levels with enzyme-linked immunosorbent assay and analyzed the expression of key proteins in the MAPK signaling pathway via western blot.RESULTS Administration of CTX led to significant damage to the bone marrow’s structural integrity and a reduction in hematopoietic cells,establishing a model of AA.Ginsenoside Rg1 successfully reversed hematopoietic dysfunction in AA mice.In comparison to the AA group,ginsenoside Rg1 provided relief by reducing the induction of cell apoptosis and inflammation factors caused by CTX.Furthermore,it helped alleviate the blockade in the cell cycle.Treatment with ginsenoside Rg1 significantly alleviated myelosuppression in mice by inhibiting the MAPK signaling pathway.CONCLUSION This study suggested that ginsenoside Rg1 addresses AA by alleviating myelosuppression,primarily through modulating the MAPK signaling pathway,which paves the way for a novel therapeutic strategy in treating AA,highlighting the potential of ginsenoside Rg1 as a beneficial intervention.

Bowel inflammatory presentations on computed tomography in adult patients with severe aplastic anemia during flared inflammatory episodes

BACKGROUND Patients with severe aplastic anemia(SAA)frequently present with inflammatory episodes,and during flared inflammatory episodes,hematopoietic function is further exacerbated.The gastrointestinal tract is the most common site for infectious and inflammatory diseases,and its structural and functional features confer on it the most potent capacity to affect hematopoietic and immune functions.Computed tomography(CT)is a readily accessible approach to provide highly useful information in detecting morphological changes and guiding further work-ups.AIM To explore CT imaging presentations of gut inflammatory damage in adult SAA patients during inflammatory episodes.METHODS We retrospectively evaluated the abdominal CT imaging presentations of 17hospitalized adult patients with SAA in search of the inflammatory niche when they presented with systemic inflammatory stress and exacerbated hematopoietic function.In this descriptive manuscript,the characteristic images that suggested the presence of gastrointestinal inflammatory damage and related imaging presentations of individual patients were enumerated,analyzed and described.RESULTS All eligible patients with SAA had CT imaging abnormalities that suggested the presence of an impaired intestinal barrier and increased epithelial permeability.The inflammatory damages were concurrently present in the small intestine,the ileocecal region and the large intestines.Some readily identified imaging signs,such as bowel wall thickening with mural stratification(“water holo sign”,“fat holo sign”,intramural gas and subserosal pneumatosis)and mesenteric fat proliferation(fat stranding and“creeping fat sign”),fibrotic bowel wall thickening,“balloon sign”,rugged colonic configuration,heterogeneity in the bowel wall texture,and adhered and clustered small bowel loop(including various patterns of“abdominal cocoon”),occurred at a high incidence,which suggested that the damaged gastrointestinal tract is a common inflammatory niche responsible for the systemic inflammatory stresses and the exacerbated hematopoietic failure in patients with SAA.Particularly,the“fat holo sign”was present in 7 patients,a rugged colonic configuration was present in 10 patients,the adhesive bowel loop was present in 15 patients,and extraintestinal manifestations suggestive of tuberculosis infections were present in 5 patients.According to the imaging features,a suggestive diagnosis of Crohn’s disease was made in 5patients,ulcerative colitis in 1 patient,chronic periappendiceal abscess in 1 patient,and tuberculosis infection in 5 patients.Other patients were diagnosed with chronic enteroclolitis with acutely aggravated inflammatory damage.CONCLUSION Patients with SAA had CT imaging patterns that suggested the presence of active chronic inflammatory conditions and aggravated inflammatory damage during flared inflammatory episodes.

Leukemic transformation during anti-tuberculosis treatment in aplastic anemia-paroxysmal nocturnal hemoglobinuria syndrome:A case report and review of literature

BACKGROUND Accumulating evidence demonstrates that autoimmune hematopoietic failure and myeloid neoplasms have an intrinsic relationship with regard to clonal hematopoiesis and disease evolution.In approximately 10%-15%of patients with severe aplastic anemia(SAA),the disease phenotype is transformed into myeloid neoplasms following antithymocyte globulin plus cyclosporine-based immunosuppressive therapy.In some of these patients,myeloid neoplasms appear during or shortly after immunosuppressive therapy.Leukemic transformation in SAA patients during anti-tuberculosis treatment has not been reported.CASE SUMMARY A middle-aged Chinese female had a 6-year history of non-SAA and a 2-year history of paroxysmal nocturnal hemoglobinuria(PNH).With aggravation of systemic inflammatory symptoms,severe pancytopenia developed,and her hemoglobinuria disappeared.Laboratory findings in cytological,immunological and cytogenetic analyses of bone marrow samples met the diagnostic criteria for“SAA.”Definitive diagnosis of disseminated tuberculosis was made in the search for infectious niches.Remarkable improvement in hematological parameters was achieved within 1 mo of anti-tuberculosis treatment,and complete hematological remission was achieved within 4 mo of treatment.Frustratingly,the hematological response lasted for only 3 mo,and pancytopenia reemerged.At this time,cytological findings(increased bone marrow cellularity and an increased percentage of myeloblasts that accounted for 16.0%of all nucleated hematopoietic cells),immunological findings(increased percentage of cluster of differentiation 34+cells that accounted for 12.28%of all nucleated hematopoietic cells)and molecular biological findings(identification of somatic mutations in nucleophosmin-1 and casitas B-lineage lymphoma genes)revealed that“SAA”had transformed into acute myeloid leukemia with mutated nucleophosmin-1.The transformation process suggested that the leukemic clones were preexistent but were suppressed in the PNH and SAA stages,as development of symptomatic myeloid neoplasm through acquisition and accumulation of novel oncogenic mutations is unlikely in an interval of only 7 mo.Aggravation of inflammatory stressors due to disseminated tuberculosis likely contributed to the repression of normal and leukemic hematopoiesis,and the relief of inflammatory stressors due to anti-tuberculosis treatment contributed to penetration of neoplastic hematopoiesis.The concealed leukemic clones in the SAA and PNH stages raise the possibility of an inflammatory stress-fueled antileukemic mechanism.CONCLUSION Aggravated inflammatory stressors can repress normal and leukemic hematopoiesis,and relieved inflammatory stressors can facilitate penetration of neoplastic hematopoiesis.

Hematopoietic stem cell transplantation of aplastic anemia by relative with mutations and normal telomere length: A case report

BACKGROUND Immunosuppressive therapy and matched sibling donor hematopoietic stem cell transplantation(MSD-HSCT)are the preferred treatments for aplastic anemia(AA).CASE SUMMARY In this report,we describe a 43-year-old male patient with severe AA who carried BRIP1(also known as FANCJ),TINF2,and TCIRG1 mutations.Screening of the family pedigree revealed the same TINF2 mutation in his mother and older brother,with his older brother also carrying the BRIP1 variant and demonstrating normal telomere length and hematopoietic function.The patient was successfully treated with oral cyclosporine A,eltrombopag,and acetylcysteine,achieving remission 4 years after receiving MSD-HSCT from his older brother.CONCLUSION This case provides a valuable clinical reference for individuals with suspected pathogenic gene mutations,normal telomere length,and hematopoietic function,highlighting them as potential donors for patients with AA.

Construction of gene/protein interaction networks and enrichment pathway analysis for paroxysmal nocturnal hemoglobinuria and aplastic anemia

Background:To develop a protein-protein interaction network of Paroxysmal nocturnal hemoglobinuria(PNH)and Aplastic anemia(AA)based on genetic genes and to predict pathways underlying the molecular complexes in the network.Methods:In this research,the PNH and AA-related genes were screened through Online Mendelian Inheritance in Man(OMIM).The plugins and Cytoscape were used to search literature and build a protein-protein interaction network.Results:The protein-protein interaction network contains two molecular complexes that are five higher than the correlation integral values.The target genes of this study were obtained:CD59,STAT3,TERC,TNF,AKT1,C5AR1,EPO,IL6,IL10 and so on.We also found that many factors regulate biological behaviors:neutrophils,macrophages,vascular endothelial growth factor,immunoglobulin,interleukin,cytokine receptor,interleukin-6 receptor,tumor necrosis factor,and so on.This research provides a bioinformatics foundation for further explaining the mechanism of common development of both.Conclusion:This indicates that the PNH and AA is a complex process regulated by many cellular pathways and multiple genes.

Spectrum of anemia associated with chronic liver disease

Anemia of diverse etiology is a common complication of chronic liver diseases. The causes of anemia include acute or chronic gastrointestinal hemorrhage, and hypersplenism secondary to portal hypertension. Severe hepatocellular disease predisposes to hemorrhage because of impaired blood coagulation caused by deficiency of blood coagulation factors synthesized by hepatocytes, and/or thrombocytopenia. Aplastic anemia, which is characterized by pancytopenia and hypocellular bone marrow, may follow the development of hepatitis. Its presentation includes progressive anemia and hemorrhagic manifestations. Hematological complications of combination therapy for chronic viral hepatitis include clinically signif icant anemia, secondary to treatment with ribavirin and/or interferon. Ribavirininduced hemolysis can be reversed by reducing the dose of the drug or discontinuing it altogether. Interferons may contribute to anemia by inducing bone marrow suppression. Alcohol ingestion is implicated in the pathogenesis of chronic liver disease and may contribute to associated anemia. In patients with chronic liver disease, anemia may be exacerbated by defi ciency of folic acid and/or vitamin B12 that can occur secondary to inadequate dietary intake or malabsorption.

Excellent response of severe aplastic anemia to treatment of gut inflammation: A case report and review of the literature

BACKGROUND Cumulative evidence suggests that the aberrant immune responses in acquired aplastic anemia(AA) are sustained by active chronic infections in genetically susceptible individuals. Recently, the constant source to trigger and sustain the pathophysiology has been proposed to come from the altered gut microbiota and chronic intestinal inflammation. In this case, our serendipitous finding provides convincing evidence that the persistently dysregulated autoimmunity may be generated, at least in a significant proposition of AA patients, by the altered gut microbiota and compromised intestinal epithelium.CASE SUMMARY A 30-year-old Chinese male patient with refractory severe AA experienced a 3-month-long febrile episode, and his fever was refractory to many kinds of injected broad-spectrum antibiotics. When presenting with abdominal cramps, he was prescribed oral mannitol and gentamycin to get rid of the gut infection. This treatment resulted in a quick resolution of the fever. Unanticipatedly, it also produced an excellent hematological response. He had undergone three episodes of recurrence within the one-year treatment, with each recurrence occurring 7-8 wk from the gastrointestinal inflammation eliminating preparations. However,subsequent treatments were able to produce subsequent remissions and consecutive treatments were successful in achieving durative hematological improvements, strongly indicating an etiological association between chronic gut inflammation and the development of AA. Interestingly, comorbid diseases superimposed on this patient(namely, psychiatric disorders, hypertension,insulin resistance, and renal dysfunction) were ameliorated together with the hematological improvements.CONCLUSION Chronic gut inflammation may be responsible for AA pathogenesis. The comorbidities and AA may share a common etiological association.

Diabetes mellitus increases the prevalence of anemia in patients with chronic kidney disease:A nested case-control study

AIM: To compare anemia prevalence between matched chronic kidney disease(CKD) patients with and without diabetes mellitus(DM) and to assess factors associated with anemia development.METHODS: This is a nested case-control study of 184 type-2 diabetic and 184 non-diabetic CKD patients from a prospectively assembled database of a Nephrology outpatient clinic, matched for gender, age and estimated glomerular filtration rate(eG FR). Prevalence of anemia(hemoglobin: Men: < 13 g/dL, women: < 12 g/dL and/or use of recombinant erythropoietin) was examined in comparison, in the total population and by CKD Stage. Univariate and multivariate logistic regression analyses were conducted to identify factors associated with anemia.RESULTS: The total prevalence of anemia was higher in diabetics(47.8% vs 33.2%, P = 0.004). Accordingly, prevalence was higher in diabetics in CKD Stage 3(53.5% vs 33.1%, P < 0.001) and particularly in Stage 3a(60.4% vs 26.4%, P < 0.001), whereas it was nonsignificantly higher in Stage 4(61.3% vs 48.4%; P = 0.307). Serum ferritin was higher in diabetics in total and in CKD stages, while serum iron was similar between groups. In multivariate analyses, DM(OR = 2.206, 95%CI: 1.196-4.069), CKD Stages 3a, 3b, 4(Stage 4: OR = 12.169, 95%CI: 3.783-39.147) and serum iron(OR = 0.976, 95%CI: 0.968-0.985 per mg/d L increase) were independently associated with anemia.CONCLUSION: Prevalence of anemia progressively increases with advancing stages of CKD and is higher in diabetic than matched non-diabetic CKD patients and diabetes is independently associated with anemia occurrence. Detection and treatment of anemia in diabetic CKD patients should be performed earlier than non-diabetic counterparts.

Expression of Adherent Molecule and Cyclin by Ligustrazine in Bone Marrow of Mice with Immune-Induced Aplastic Anemia

Summary: Mice with immune induced aplastic anemia (AA) were given 5 mg ligustrazine intraperitoneally twice a day. On the 14th day, the expression of CD 49d , CD 49e , cyclinD 2 in bone marrow mononuclear cells (MNC) was examined by flow cytometry, and VCAM 1 on stromal cells was immunohistochemically measured by Strept Avidin Biotin Complex (SABC). The expression of CD 49d , CD 49e , VCAM 1 and cyclinD 2 in ligustrazine treated group was significantly higher than that in AA group ( P <0 01), but the ratio of G 0+G 1 phase cells was significantly lower than that in AA group ( P <0.01).The results showed that ligustrazine could improve the expression of adherent molecule and cyclin D 2 in the bone marrow of mice with immune induced aplastic anemia, thereby promoting the growth of hematopoietic cells.

Proliferation and Apoptosis of Bone Marrow CD4^+ T Cells in Patients with Aplastic Anemia and Impacts of the Secreted Cytokines on Hematopoietic Stem Cells from Umbilical Cord Blood

Recent studies indicate that immune-associated aplastic anemia(AA)resembles such autoimmune diseases as insulin-dependent diabetes and chronic autoimmune thyroiditis that belong to organ-specific autoimmune diseases.Many independent investigation groups have successfully isolated the pathopoiesis-associated T cell clone causing hematopoiesis failure with a CD4 phenotype from peripheral blood and bone marrow(BM)in AA patients.In the current study,BM CD4+ T cells were isolated from AA patients and healthy con...

Electrophysiological changes of autonomic cells in left ventricular outflow tract in guinea pigs with iron deficiency anemia complicated with chronic heart failure

Objective: To investigate the electrophysiological changes of autonomic cells in left ventricular outflow tract in guinea pigs with iron deficiency anemia complicated with chronic heart failure.Methods: Guinea pigs model of iron deficiency anemia complicated with chronic heart failure in 10 guinea pigs of the experimental group was made by feeding a low iron diet,pure water and subcutaneous injection of isoproterenol. The control group consisting of 11 guinea pigs was given normal food, normal water and injected with normal saline. The left ventricular outflow tract model specimen was also prepared. The standard microelectrode technique was used to observe electrophysiological changes of autonomic cells in the outflow tract of left ventricular heart failure complicated with iron deficiency anemia in guinea pig model. The indicators of observation were maximal diastolic potential, action potential amplitude, 0 phase maximal depolarization velocity, 4 phase automatic depolarization velocity, repolarization 50% and 90%, and spontaneous discharge frequency.Results: Compared with the control group, 4 phase automatic depolarization velocity,spontaneous discharge frequency and 0 phase maximal depolarization velocity decreased significantly(P < 0.01) and action potential amplitude reduced(P < 0.01) in model group. Moreover, repolarization 50% and 90% increased(P < 0.01).Conclusions: There are electrophysiological abnormalities of the left ventricular outflow tract in guinea pigs with iron deficiency anemia complicated with heart failure.

Yin and Yang of mesenchymal stem cells and aplastic anemia

Acquired aplastic anemia(AA) is a bone marrow failure syndrome characterized by peripheral cytopenias and bone marrow hypoplasia. It is ultimately fatal without treatment, most commonly from infection or hemorrhage. Current treatments focus on suppressing immune-mediated destruction of bone marrow stem cells or replacing hematopoietic stem cells(HSCs) by transplantation. Our incomplete understanding of the pathogenesis of AA has limited development of targeted treatment options. Mesenchymal stem cells(MSCs) play a vital role in HSC proliferation; they also modulate immune responses and maintain an environment supportive of hematopoiesis. Some of the observed clinical manifestations of AA can be explained by mesenchymal dysfunction. MSC infusions have been shown to be safe and may offer new approaches for the treatment of this disorder. Indeed, infusions of MSCs may help suppress auto-reactive, T-cell mediated HSC destruction and help restore an environment that supports hematopoiesis. Small pilot studies using MSCs as monotherapy or as adjuncts to HSC transplantation have been attempted as treatments for AA. Here we review the current understanding of the pathogenesis of AA and the function of MSCs, and suggest that MSCs should be a target for further research and clinical trials in this disorder.

Role of Stem Cell Factor and Its Receptor in the Pathogenesis of Pediatric Aplastic Anemia

In order to investigate the levels of stem cell factor (SCF) and its receptor c-kit protein and mRNA in pediatric aplastic anemia (AA) and their relevance to the pathogenesis, immunocytochemical and in situ hybridization were utilized to detect the expression of SCF and its receptor c-kit gene protein and mRNA, respectively in 59 children with AA and 51 normal controls. The relationship between SCF and c-kit and the pathogenesis of AA was analyzed subsequently. The results showed that the positive rate of SCF protein and mRNA expression in children with AA was significantly lower than that in healthy controls (P<0.05). However, there was no significant difference in the positive rate of c-kit protein and mRNA expression between children with AA and control group (P>0.05). It was concluded that the expression of SCF is significantly decreased in children with AA, which may be closely associated with the pathogenesis of the AA. c-kit may be unrelated to the development of pediatric AA. Therefore, AA in children may have abnormalities at SCF/c-kit signal transduction levels.

Effects of H pylori therapy on erythrocytic and iron parameters in iron deficiency anemia patients with H pylori-positive chronic gastristis

AIM： To elucidate the influences of Hpylori infection on oral iron treatment for iron deficiency anemia （IDA）.METHODS： A total of 86 patients were divided into two groups： group A, receiving ferrous succinate combined with triple therapy for H pylori eradication, and group B （control）, treated with ferrous succinate only. During treatment of IDA, dynamic changes in hemoglobin （Hb） level, mean corpuscular volume （MCV）, mean corpuscular hemoglobin （MCH）, serum iron （SI）, and serum ferritin （SF） were compared between the groups.RESULTS： Hb was slightly higher in group A at d 14 alter the start of triple therapy for H pylori eradication （P 〉 0.05）. After the therapy, the increase of Hb in group A became significantly faster than that in group B （P 〈 0.05）. At d 56, the mean Hb in group A returned to the normal level, however, in group B, it was lower than that in group A （P 〈 0.05） although it had also increased compared with that before oral iron treatment. The MCV and MCH in group A recovered to the normal level, and were much higher than those in group B （P 〈 0.05） at d 21. In Group B, the MCV and MCH remained at lower than normal levels until d 42 alter the start of therapy. And then, they reached a plateau in both groups and the differences disappeared （P 〉 0.05）. The SF in group A was higher than that in group B （P 〈 0.05） 28 d alter the treatment and its improvement was quicker in group A （P 〈 0.05）, and the difference between the two groups was even more significant （P 〈 0.01） at d 56. The SI in group A was higher than that in group B （P 〈 0.05） at d 14 and this persisted until d 56 when the follow-up of this research was finished.CONCLUSION： Treatment of H pylori can enhance the efficacy of ferrous succinate therapy in IDA patients with Hpylori-positive chronic gastritis.

Small bowel racemose hemangioma complicated with obstruction and chronic anemia:A case report and review of literature

BACKGROUND Gastrointestinal hemangiomas are rare benign tumors.According to the size of the affected vessels,hemangiomas are histologically classified into cavernous,capillary,or mixed-type tumors,with the cavernous type being the most common and racemose hemangiomas being very rare in the clinic.Melena of uncertain origin and anemia are the main clinical manifestations,and other presentations are rare.Due to the rarity of gastrointestinal hemangiomas and lack of specific manifestations and diagnostic methods,preoperative diagnoses are often delayed or incorrect.CASE SUMMARY We report a 5-year-old girl who presented with abdominal pain,nausea,and vomiting for a duration of 10 h.The laboratory studies showed prominent anemia.Computed tomography and contrast-enhanced computed tomography of the abdomen revealed a small bowel obstruction caused by a giant abdominal mass.Segmental resection of the ileal lesions was performed through surgery,and the final pathology results revealed a diagnosis of racemose hemangioma complicated by a small bowel obstruction and simultaneous chronic anemia.CONCLUSION The current report will increase the understanding of the diagnosis and treatment of gastrointestinal hemangiomas and provide a review of the related literature.

Effects of hypoxia on bone metabolism and anemia in patients with chronic kidney disease

BACKGROUND Abnormal bone metabolism and renal anemia seriously affect the prognosis of patients with chronic kidney disease(CKD).Existing studies have mostly addressed the pathogenesis and treatment of bone metabolism abnormality and anemia in patients with CKD,but few have evaluated their mutual connection.Administration of exogenous erythropoietin to CKD patients with anemia used to be the mainstay of therapeutic approaches;however,with the availability of hypoxia-inducible factor(HIF)stabilizers such as roxadustat,more therapeutic choices for renal anemia are expected in the future.However,the effects posed by the hypoxic environment on both CKD complications remain incompletely understood.AIM To summarize the relationship between renal anemia and abnormal bone metabolism,and to discuss the influence of hypoxia on bone metabolism.METHODS CNKI and PubMed searches were performed using the key words“chronic kidney disease,”“abnormal bone metabolism,”“anemia,”“hypoxia,”and“HIF”to identify relevant articles published in multiple languages and fields.Reference lists from identified articles were reviewed to extract additional pertinent articles.Then we retrieved the Abstract and Introduction and searched the results from the literature,classified the extracted information,and summarized important information.Finally,we made our own conclusions.RESULTS There is a bidirectional relationship between renal anemia and abnormal bone metabolism.Abnormal vitamin D metabolism and hyperparathyroidism can affect bone metabolism,blood cell production,and survival rates through multiple pathways.Anemia will further attenuate the normal bone growth.The hypoxic environment regulates bone morphogenetic protein,vascular endothelial growth factor,and neuropilin-1,and affects osteoblast/osteoclast maturation and differentiation through bone metabolic changes.Hypoxia preconditioning of mesenchymal stem cells(MSCs)can enhance their paracrine effects and promote fracture healing.Concurrently,hypoxia reduces the inhibitory effect on osteocyte differentiation by inhibiting the expression of fibroblast growth factor 23.Hypoxia potentially improves bone metabolism,but it still carries potential risks.The optimal concentration and duration of hypoxia remain unclear.CONCLUSION There is a bidirectional relationship between renal anemia and abnormal bone metabolism.Hypoxia may improve bone metabolism but the concentration and duration of hypoxia remain unclear and need further study.

Trichosporon asahii ankle cavity effusion infection in a patient with severe aplastic anemia

Rationale:Trichosporon,an anamorphic fungus,proliferates under high humidity,causing serious opportunistic infections collectively called trichosporonosis.Among the Trichosporon species causing trichosporonosis are Trichosporon(T.)asahii,T.asteroides,T.cutaneum etc.Patient concerns:A 38-year-old Chinese male with severe aplastic anemia was admitted due to multiple joints pain,poor appetite,and right ankle swelling.One year earlier he had undergone allogeneic hematopoietic stem cell transplantation.Diagnosis:T.asahii infection and severe aplastic anemia.Interventions:Combined treatment of amphotericin B liposomes(55 mg/24 h)and voriconazole(200 mg/12 h)for 8 days.Outcomes:The symptoms of the patient’s ankle were relieved and effusion cultures showed no T.asahii.Lessons:To the best of our knowledge,T.asahii ankle cavity effusion infections are rare.Trichosporon infections may be attributed to risk factors such as improper long-term use of antimicrobials for an underlying disease(e.g.,anemia,hypoalbuminemia).Attention should be paid to prevent and control Trichosporon infections in order to avoid comorbidities.

Effects of Serum from Aplastic Anemia patients on the Expression of Cyclin D3 Isoform in Umbilical Cord Blood CD34^+ Cells

Summary: The pathogenesis of aplastic anemia (AA) was explored and the effects of AA serum on the expression of crucial cyclin D isoform (cyclin D3) in umbilical cord blood hematopoietic stem/progenitor cells were observed. The CD34+ cells were isolated from the cord blood with MIDI-MACS Semi-solid methylcellulose culture technique was used to measure the formation of CFU-GM; The expression level of cyclin D3 was assayed by semi-quantitative RT-PCR and Western-blot after the hematopoietic stem/progenitor cells were incubated in AA serum. The results showed that the AA serum could inhibit the formation of CFU-GM and down regulate the expression level of the cyclin D3 at the mRNA and protein level respectively. In conclusion, the AA serum could inhibit the proliferation of hematopoietic stem cells and down regulate level of cyclin D3, which might be one mechanism of hematopoiesis inhibition in AA.