Objective Acquired aplastic anemia(aAA)is characterized by an autologous immunological attack against hematopoietic stem and progenitor cells,and immunotolerance disruption is frequent,with reduced T regulatory cells(...Objective Acquired aplastic anemia(aAA)is characterized by an autologous immunological attack against hematopoietic stem and progenitor cells,and immunotolerance disruption is frequent,with reduced T regulatory cells(Tregs)frequencies and increased effector cytotoxic cells.Tregs are reduced in aAA and increase in number after successful immunosuppressive therapies.Methods In this retrospective study,we investigated the frequency of circulating Tregs by multiparametric flow cytometry immunophenotyping in non-severe aAA patients before and after immunosuppressive therapy.The samples were stained with the following antibodies:ECD anti-CD3,PE or PC5 anti-CD4,FITC anti-CD8,and PE anti-CD25,and Tregs were identified by first gating on linear parameters for lymphocyte identification and then for CD3 expression.In CD3+CD4+cells,Tregs were further identified on the basis of CD25 and FOXP3 expression.Results Although the number of Tregs tended to increase after immunosuppressive treatments,their circulating frequency remained lower than that of healthy subjects,regardless of their responsiveness to therapies.Moreover,the relative frequency combined with absolute Treg counts might be more informative in the differential diagnosis of bone marrow failure syndromes.Conclusions The persistent decrease in circulating Tregs could be the result of immunosuppressive agents that could preferentially expand other T-cell subsets.At the same time,an imbalance in immunotolerance might persist,which is also favored by chronic antigen stimulation.展开更多
Objective:To observe the effects of moxibustion on the hematopoietic function in mice with aplastic anemia(AA)induced by bone marrow(BM)suppression,and to investigate the intervention effects of moxibustion on AA from...Objective:To observe the effects of moxibustion on the hematopoietic function in mice with aplastic anemia(AA)induced by bone marrow(BM)suppression,and to investigate the intervention effects of moxibustion on AA from the perspective of intestinal bacteria.Methods:A total of 24 C57BL/6 J male mice were randomly and evenly divided into control,model and moxibustion groups.The myelosuppression-induced AA model was established by cyclophosphamide(CTX)and cyclosporine(Cs)intraperitoneal injection.Mice in the moxibustion group were intervened in mild moxibustion at unilateral“Zusanli(ST36)”acupoint for 15 min per day,and the sides were switched the next day.The intervention of mild moxibustion lasted 60 days consecutively.The red blood cell(RBC),white blood cell(WBC),platelet(PLT)counts and haemoglobin(Hb)concentration levels of mice in each group were detected by peripheral blood cells count staining,and the BM hematopoietic cells and hematopoietic structures were observed by BM smear Wright-Giemsa staining and HE staining.16SrDNA sequencing was used to analyze the gut bacterial species abundance and diversity in mice from each group.Results:After all the intervention,compared to the control group,the model group had lower levels of RBC,WBC,PLT counts and Hb concentration in peripheral blood(P<0.05)and fewer hematopoietic cells and hematopoietic structures;compared to the model group,moxibustion group had higher levels of RBC,WBC,PLT counts and Hb concentration in peripheral blood(P<0.05),and more BM hematopoietic cells and hematopoietic structures.Gut flora showed that moxibustion increased the species richness and diversity of intestinal bacteria in mice;compared with the control group,the relative abundance of Faecalibaculum and Anaeroplasmataceae in the model group was higher(P<0.05);whereas,the relative abundance of Faecalibaculum and Anaeroplasmataceae in the moxibustion group was lower(P<0.05)when compared with the model group.In addition,Faecalibaculum was significantly correlated with RBC,WBC,PLT count and Hb concentration(P<0.05).Conclusion:Moxibustion can improved BM histology,restored hematopoietic cells function,and increased peripheral blood cells count and Hb concentration in AA mice.The mechanism may be related to the fact that moxibustion regulates the abundance of specific intestinal bacteria to maintain the stability of the flora structure.展开更多
OBJECTIVE:To investigate the effect of Shisiwei Jianzhong decoction(十四味建中汤,SJD)on non-severe aplastic anemia(NSAA).METHODS:Bone marrow mesenchymal stem cells(BMSCs)were isolated from bone marrow samples of 15 NS...OBJECTIVE:To investigate the effect of Shisiwei Jianzhong decoction(十四味建中汤,SJD)on non-severe aplastic anemia(NSAA).METHODS:Bone marrow mesenchymal stem cells(BMSCs)were isolated from bone marrow samples of 15 NSAA patients and 3 healthy controls.Cells were treated with gradient concentrations of SJD,and a portion was transfected with a vector overexpressing the nuclear factor of activated T cells,cytoplasmic 4(NFATC4).Cell viability and apoptosis were detected by cell counting kit-8 and flow cytometry,respectively.After adipogenic differentiation induction,lipid droplet formation in BMSCs was examined by Oil Red O staining.The expression of NFATC4,peroxisome proliferator-activated receptor gamma(PPARG),fatty acid-binding protein 4(FABP4),peroxisome proliferator-activated receptor-gamma coactivator(PGC-1α),and acetylated PGC-1αwas measured by quantitative real-time polymerase chain reaction or Western blot.RESULTS:SJD significantly increased the viability and decreased the apoptosis of NSAA-derived BMSCs.It also dose-dependently inhibited lipid droplet formation and decreased the expression of PPARG and FABP4 in NSAA-derived BMSCs.NFATC4 expression was higher in patients with NSAA than in healthy controls,and SJD downregulated its expression.NFATC4 overexpression reversed the inhibitory effect of SJD on adipogenic differentiation.Additionally,SJD promoted the deacetylation of PGC-1αin NSAA-derived BMSCs,which was also partially eliminated by NFATC4 overexpression.CONCLUSIONS:SJD inhibits adipogenic differentiation of BMSCs through downregulating NFATC4,thereby contributing to the remission of NSAA.展开更多
To investigate the efficacy of a structured continuous nursing intervention program on clinical outcomes,self-efficacy,and sleep quality in patients diagnosed with aplastic anemia(AA).Methods:This study was a single-c...To investigate the efficacy of a structured continuous nursing intervention program on clinical outcomes,self-efficacy,and sleep quality in patients diagnosed with aplastic anemia(AA).Methods:This study was a single-center,parallel-group,randomized controlled trial.A total of 64 patients with AA,treated at our hospital’s hematology department from May 2022 to May 2025,were enrolled.Participants were randomly allocated in a 1:1 ratio to either the control group(n=32),receiving routine nursing care,or the intervention group(n=32),receiving a six-month continuous nursing intervention program in addition to routine care.The intervention program consisted of structured health education,individualized psychological support,regular telephone follow-ups,and a 24/7 online communication platform.The primary outcome was the change in the Pittsburgh Sleep Quality Index(PSQI)score from baseline to six months.Secondary outcomes included hematological parameters(hemoglobin[Hb],absolute neutrophil count[ANC],platelet count[PLT]),incidence of adverse events(infections,bleeding episodes),quality of life(assessed by the Functional Assessment of Cancer Therapy–Anemia[FACT-An]),and self-efficacy(assessed by the General Self-Efficacy Scale[GSE]).Statistical analyses were performed using independent t-tests,and chi-square tests or Fisher’s exact tests as appropriate.Results:A total of 55 patients(28 in the intervention group and 27 in the control group)completed the study.At baseline,there were no statistically significant differences in demographic data,clinical characteristics,or outcome measures between the two groups(p>0.05).After six months,the mean PSQI score in the intervention group was significantly lower than that in the control group(7.12±2.05 vs.13.49±2.88;t=−13.450;p<0.001).The intervention group also demonstrated a significantly lower incidence of infections(4/28,14.29%vs.10/27,37.04%;p=0.048)and bleeding episodes requiring intervention(3/28,10.71%vs.9/27,33.33%;p=0.042).Furthermore,patients in the intervention group reported significantly higher scores on the FACT-An(125.70±10.31 vs.109.44±12.10;t=7.934;p<0.001)and the GSE scale(29.82±4.11 vs.23.51±4.80;t=7.311;p<0.001).While hematological parameters showed a trend toward improvement in the intervention group,the differences were not statistically significant compared to the control group(p>0.05).Conclusion:The implementation of a structured continuous nursing intervention program can significantly improve sleep quality,reduce the incidence of complications,and enhance quality of life and self-efficacy in patients with aplastic anemia.This evidence-based model of care should be considered for integration into standard clinical practice for the long-term management of this patient population.展开更多
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 T...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.展开更多
Aplastic anemia(AA)is a rare but serious condition in which the bone marrow fails to produce sufficient new blood cells,leading to fatigue,increased susceptibility to infection,and uncontrolled bleeding.In this editor...Aplastic anemia(AA)is a rare but serious condition in which the bone marrow fails to produce sufficient new blood cells,leading to fatigue,increased susceptibility to infection,and uncontrolled bleeding.In this editorial,we review and comment on an article by Wang et al published in 2024.This study aimed to evaluate the potential therapeutic benefits of ginsenoside Rg1 in AA,focusing on its protective effects and uncovering the underlying mechanisms.Cyclophosphamide(CTX)administration caused substantial damage to the structural integrity of the bone marrow and decreased the number of hematopoietic stem cells,thereby establishing an AA model.Compared with the AA group,ginsenoside Rg1 alleviated the effects of CTX by reducing apoptosis and inflammatory factors.Mechanistically,treatment with ginsenoside Rg1 significantly mitigated myelosuppression in mice by inhibiting the mitogen activated protein kinase signaling pathway.Thus,this study indicates that ginsenoside Rg1 could be effective in treating AA by reducing myelosuppression,primarily through its influence on the mitogen activated protein kinase signaling pathway.We expect that our review and comments will provide valuable insights for the scientific community related to this research and enhance the overall clarity of this article.展开更多
Aplastic anemia (AA) is a rare, life-threatening disease characterized by pancytopenia and bone marrow failure. However, since the introduction of immunosuppressive therapy and allogeneic stem cell transplantation, ou...Aplastic anemia (AA) is a rare, life-threatening disease characterized by pancytopenia and bone marrow failure. However, since the introduction of immunosuppressive therapy and allogeneic stem cell transplantation, outcomes have improved considerably, with 5-year survival reported to be 70% - 90%. In Congo, contemporary data on survival are lacking. We performed a retrospective study to describe the epidemiological, diagnostic, and therapeutic characteristics of patients with AA diagnosed in the clinical hematology department of the University Hospital of Brazzaville from 2017 to 2023. Chemically induced aplasia was excluded from the study. The CAMITTA criteria were used to classify the severity of AA. In total, 45 confirmed cases were identified, and 35 files provided sufficient data for the descriptive study. The median age was 26 years (range: 1 - 50). Adults made up 75% of the study population. The sex ratio was 1.05 (0.5 in children and 1.17 in adults). One case of AA was secondary to treatment with imatinib mesylate;the other cases (97.1%) were idiopathic. Pancytopenia was present in all patients. Moderate, severe, and very severe AA represented 11.4%, 74.3%, and 14.3% of cases, respectively. Severe and very severe forms were more frequent in adults (77.4% vs. 22.6%) and in men. Nine patients (26%) received cyclosporine monotherapy. Only one received treatment regularly and obtained the only favorable response. No patient received ATG or eltrombopag. Hemorrhagic syndrome was the most common cause of death (4 out of 6 cases) due to the unavailability of platelet concentrates. Eighteen patients (51.4% of cases) were lost to follow-up. The median follow-up was 28.7 (1 - 96) months. In conclusion, the prognosis of AA remains poor and could be improved with affordable immunosuppressive treatments, availability of platelet concentrates, and implementation of allogeneic bone marrow transplantation.展开更多
Objective:To explore the difference of lymphocyte subsets in peripheral blood(PB)between aplastic anemia(AA)and hypoplastic myelodysplastic syndrome(hypo-MDS)patients,meanwhile to compare the clinical parameters obtai...Objective:To explore the difference of lymphocyte subsets in peripheral blood(PB)between aplastic anemia(AA)and hypoplastic myelodysplastic syndrome(hypo-MDS)patients,meanwhile to compare the clinical parameters obtained from PB and bone marrow(BM).Methods:The lymphocyte subsets in hypo-MDS(n=25)and.AA(n=33)patients were investigated by flow cytometry.Meanwhile,the differences in PB cell counts,biochemical indicators,BM cell counts and abnormal chromosomes between the two groups were analyzed.Results:The percentage of CD8^(+)T cells in AA group was significantly higher than that in hypo-MDS group(P=0.001),while the percentage of CD4^(+)T cells and the CD4^(+)/CD8^(+)ratio in AA group were obviously lower than those in hypo-MDS group(P=0.015 and 0.001,respectively).Furthermore,the proportion of CD4^(+)and CD8^(+)activated T(TA)cells,and memory Tregs in AA group was distinctly lower than those in hypo-MDS group(P=0.043,0.015 and 0.024,respectively).Nevertheless,the percentage of CD8^(+)naive T(TN)cells in AA patients was remarkably higher(P=0.044).And hypo-MDS patients had declined lymphocyte counts(P=0.025),increased levels of total bilirubin(TBil),lactate dehydrogenase(LDH),vitamin B12 and proportion of BM blasts than AA patients(P=0.019,0.023,0.027 and.0.045,respectively).Conclusion:In this study it was confirmed that the percentages of CD4^(+)and CD8^(+)TA cells,memory Tregs and CD8^(+)TN cells were significantly different between AA and hypo-MDS patients,which provide an essential basis for the identification of these two diseases.展开更多
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...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.展开更多
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. C...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.展开更多
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.M...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...展开更多
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 trea...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.展开更多
Rationale:Trichosporon,an anamorphic fungus,proliferates under high humidity,causing serious opportunistic infections collectively called trichosporonosis.Among the Trichosporon species causing trichosporonosis are Tr...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.展开更多
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 sour...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.展开更多
We previously reported a serendipitous finding from a patient with refractory severe aplastic anemia who had gotten an unexpected hematological response to treatment with gut-cleansing preparations(GCPs).This patient ...We previously reported a serendipitous finding from a patient with refractory severe aplastic anemia who had gotten an unexpected hematological response to treatment with gut-cleansing preparations(GCPs).This patient experienced three recurrences over the ensuing one year of intermittent GCP treatments,with each recurrence occurring 7-8 wk from a GCP.After his third recurrence,he was prescribed successive treatment with rifampicin,berberine,and monthly administered GCP for 4 mo,and he developed an erythroid proliferative neoplasma and an overwhelming enteropathy,and eventually died of septic shock.Laboratory investigations had validated the resolution of myelosuppression and the appearance of malignant clonal hematopoiesis.From the treatment process and laboratory investigations,it is reasonably inferred that the engagement of gut inflammation is critically required in sustaining the overall pathophysiology of acquired aplastic anemia probably by creating a chronic inflammatory state.Incorporation of rifampicin,berberine,and monthly GCP into cyclosporine can enhance the immunosuppressive effect.In a subgroup of acquired aplastic anemia patients whose pathogenesis is associated with genotoxic exposure,the suppressed normal hematopoiesis may result from the bystander insult that is mediated by the soluble inflammatory cytokines generated in response to the immunogenic products of damaged hematopoietic cells in the context of chronic inflammatory state and may offer a protective antineoplastic mechanism against malignant proliferation.展开更多
BACKGROUND Aplastic anemia(AA)complicated with myocardial infarction(MI)is rare and associated with poor prognosis.Here,we present a case of AA with recurrent acute MI(AMI)in a patient treated with cyclosporine A(CsA)...BACKGROUND Aplastic anemia(AA)complicated with myocardial infarction(MI)is rare and associated with poor prognosis.Here,we present a case of AA with recurrent acute MI(AMI)in a patient treated with cyclosporine A(CsA)and stanozolol.In this patient,we suspect the long-term use of medication linked to platelets hyperfunction.CASE SUMMARY In 2017,a 45-year-old man was rushed to the emergency department of China-Japan Union Hospital due to precordial pain for 5 h.Based on his symptoms,medical history,blood tests,and findings from coronary angiography(CAG),the patient was diagnosed with acute anterior wall,ST-segment elevated MI,Killip II grade,AA,and dyslipidemia.In 2021,the patient was readmitted to the hospital for 2 h due to chest pain.Because the patient’s platelet count was 30×109/L and he had severe thrombocytopenia,we performed CAG following platelet transfusion.Optical coherence tomography revealed lipid plaque and thrombus mass in his right coronary artery.The antithrombotic approach was adjusted to employ only anticoagulants(factor Xa inhibitors)and adenosine diphosphate inhibitors(clopidogrel)after assessing the risk of bleeding/thrombotic events.Long-term follow-up revealed that the patient had made a good recovery.CONCLUSION Patients with AA should be closely monitored for the risk of thrombosis and cardiovascularevents, particularly when taking stanozolol or CsA for an extended period of time.展开更多
BACKGROUND Hepatitis-associated aplastic anemia(HAAA) is a rare condition. Patients with HAAA usually present with acute hepatitis, jaundice and significantly increased transaminase. After 1–2 mo, hepatitis gradually...BACKGROUND Hepatitis-associated aplastic anemia(HAAA) is a rare condition. Patients with HAAA usually present with acute hepatitis, jaundice and significantly increased transaminase. After 1–2 mo, hepatitis gradually improves, but progressive hemocytopenia, bone marrow hematopoietic failure, and severe or extremely severe aplastic anemia are manifest. Most cases of HAAA are fulminant and usually lethal if left untreated. The literature on Epstein–Barr virus(EBV)-associated HAAA is sparse.CASE SUMMARY We report a 30-year-old man who was admitted to our hospital because of pale yellow urine and skin with a simultaneous decrease in peripheral blood ternary cells. We made a diagnosis of EBV-associated HAAA. The treatment strategy for this patient included eltrombopag, an immunosuppressive regimen of rabbit antihuman thymocyte immunoglobulin, cyclosporine, and supportive care. The patient was discharged in normal physical condition after five months. A hemogram performed on follow-up revealed that he had achieved a complete response.CONCLUSION Eltrombopag plus anti-thymocyte globubin and cyclosporine may be a therapeutic option for EBV-associated HAAA.Larger studies are warranted to confirm.展开更多
Objective. To explore the relationship between human parvovirus B19 (HPV B19) infection and aplastic anemia (AA) and to investigate the role of HPV B19 in the occurrence of AA. Methods. The presence of HPV B19 DNA was...Objective. To explore the relationship between human parvovirus B19 (HPV B19) infection and aplastic anemia (AA) and to investigate the role of HPV B19 in the occurrence of AA. Methods. The presence of HPV B19 DNA was detected in the peripheral blood samples of 60 patients with AA (children 38 and adults 22) by nested polymerase chain reaction (PCR) assay, and 30 healthy persons were selected as control. Results. Sixteen (26.7％ ) of 60 AA cases were HPV B19 DNA positive, while all the samples in the control group were negative for HPV B19 (P = 0.000914). Among the case group, the positive rates of HPV B19 DNA were 21.4％ (6 / 28), 30.0％ (3 / 10), 20.0％ (1 / 5) and 35.3％ (6 / 17) in children acute AA (AAA), children chronic AA (CAA), adults AAA and adults CAA patients respectively, which were significantly higher than that in the control group. Furthermore, there was no remarkable difference between children AA and adults AA in the 16 HPV B19 DNA positive patients; neither was there between AAA and CAA. Conclusions. HPV B19 infection is not only correlated with the occurrence of children AAA and CAA, but also with adults AAA and CAA, and might be an important viral cause for AA in humans.展开更多
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 obs...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.展开更多
Objective To elucidate the mechanisms underlying the therapeutic effects of Fufang Ejiao Jiang(复方阿胶浆,FFEJJ)on aplastic anemia(AA)using integrated network pharmacology and serum metabolomics.Methods Traditional Ch...Objective To elucidate the mechanisms underlying the therapeutic effects of Fufang Ejiao Jiang(复方阿胶浆,FFEJJ)on aplastic anemia(AA)using integrated network pharmacology and serum metabolomics.Methods Traditional Chinese Medicine Systems Pharmacology(TCMSP),Pubmed,integrative pharmacology-based research platform of traditional Chinese medicine(TCMIP),and Bioinformatics Analysis Tool for Molecular mech ANism of Traditional Chinese Medicine(BATMAN-TCM)were used to identify the constituents and putative targets of FFEJJ.Gene Cards and DisGeNET databases were used to identify AA-associated targets.We constructed a herb-component-target network and analyzed the protein-protein interaction(PPI)network.Potential mechanisms were determined using Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analyses.In addition,an AA model was established using acetylphenylhydrazine(APH)and cetylphenylhydrazine(CTX).Ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UPLC-QTOF/MS)-based serum metabolomics was applied to screen potential metabolites and the related pathways associated with AA and the potential anti-anemic effects of FFEJJ.Results A total of 30 active components of FFEJJ and 24 targets were related to AA.PPI network analysis showed that VEGFA,AKT1,IL-6,CASP3,and ICAM1 were key nodes overlapping with proteins known to be related to AA.KEGG pathway enrichment analysis revealed that the presumed targets of FFEJJ were mainly associated with pathways linked to the promotion of hematopoiesis and improvement of the hematopoietic microenvironment.A total of 423 metabolite biomarkers were identified between the control and AA models,which are involved in the development of AA.In contrast,FFEJJ reversed the 79 differential metabolites altered by AA.Pathway analysis suggested that the synergistic effects of FFEJJ were mainly enriched in 24 metabolic pathways.Among them,sphingolipid metabolism,glycerophospholipid metabolism,and arachidonic acid metabolism were related to promoting hematopoiesis and improving the hematopoietic microenvironment,which partially conforms with network pharmacology.The interaction network formed by three key differential metabolites,including hydroxy-eicosatetraenoic acid(HETE),sphingosine 1-phosphate(S1 P),and lysophosphatidylcholine(lyso PC),and three predicted network targets(VEGFA,CASP3,and ICAM1)may be the potential mechanism underlying the anti-AA action of the multi-component of FFEJJ.Conclusion FFEJJ could be an alternative treatment option for AA.It acts by promoting hematopoiesis and improving the hematopoietic microenvironment.Network pharmacology-integrated metabolomics makes it possible to analyze TCMs from a systems perspective and at the molecular level.展开更多
文摘Objective Acquired aplastic anemia(aAA)is characterized by an autologous immunological attack against hematopoietic stem and progenitor cells,and immunotolerance disruption is frequent,with reduced T regulatory cells(Tregs)frequencies and increased effector cytotoxic cells.Tregs are reduced in aAA and increase in number after successful immunosuppressive therapies.Methods In this retrospective study,we investigated the frequency of circulating Tregs by multiparametric flow cytometry immunophenotyping in non-severe aAA patients before and after immunosuppressive therapy.The samples were stained with the following antibodies:ECD anti-CD3,PE or PC5 anti-CD4,FITC anti-CD8,and PE anti-CD25,and Tregs were identified by first gating on linear parameters for lymphocyte identification and then for CD3 expression.In CD3+CD4+cells,Tregs were further identified on the basis of CD25 and FOXP3 expression.Results Although the number of Tregs tended to increase after immunosuppressive treatments,their circulating frequency remained lower than that of healthy subjects,regardless of their responsiveness to therapies.Moreover,the relative frequency combined with absolute Treg counts might be more informative in the differential diagnosis of bone marrow failure syndromes.Conclusions The persistent decrease in circulating Tregs could be the result of immunosuppressive agents that could preferentially expand other T-cell subsets.At the same time,an imbalance in immunotolerance might persist,which is also favored by chronic antigen stimulation.
基金Supported by the State Administration of Traditional Chinese Medicine high-level key disciplines construction project:zyyzdxk-2023068Three-year Action Plan for Shanghai TCM Development and Inheritance Program:ZY(2021-2023)-0302。
文摘Objective:To observe the effects of moxibustion on the hematopoietic function in mice with aplastic anemia(AA)induced by bone marrow(BM)suppression,and to investigate the intervention effects of moxibustion on AA from the perspective of intestinal bacteria.Methods:A total of 24 C57BL/6 J male mice were randomly and evenly divided into control,model and moxibustion groups.The myelosuppression-induced AA model was established by cyclophosphamide(CTX)and cyclosporine(Cs)intraperitoneal injection.Mice in the moxibustion group were intervened in mild moxibustion at unilateral“Zusanli(ST36)”acupoint for 15 min per day,and the sides were switched the next day.The intervention of mild moxibustion lasted 60 days consecutively.The red blood cell(RBC),white blood cell(WBC),platelet(PLT)counts and haemoglobin(Hb)concentration levels of mice in each group were detected by peripheral blood cells count staining,and the BM hematopoietic cells and hematopoietic structures were observed by BM smear Wright-Giemsa staining and HE staining.16SrDNA sequencing was used to analyze the gut bacterial species abundance and diversity in mice from each group.Results:After all the intervention,compared to the control group,the model group had lower levels of RBC,WBC,PLT counts and Hb concentration in peripheral blood(P<0.05)and fewer hematopoietic cells and hematopoietic structures;compared to the model group,moxibustion group had higher levels of RBC,WBC,PLT counts and Hb concentration in peripheral blood(P<0.05),and more BM hematopoietic cells and hematopoietic structures.Gut flora showed that moxibustion increased the species richness and diversity of intestinal bacteria in mice;compared with the control group,the relative abundance of Faecalibaculum and Anaeroplasmataceae in the model group was higher(P<0.05);whereas,the relative abundance of Faecalibaculum and Anaeroplasmataceae in the moxibustion group was lower(P<0.05)when compared with the model group.In addition,Faecalibaculum was significantly correlated with RBC,WBC,PLT count and Hb concentration(P<0.05).Conclusion:Moxibustion can improved BM histology,restored hematopoietic cells function,and increased peripheral blood cells count and Hb concentration in AA mice.The mechanism may be related to the fact that moxibustion regulates the abundance of specific intestinal bacteria to maintain the stability of the flora structure.
基金Supported by Zhejiang Province Traditional Chinese Medicine Science and Technology Plan Project:Research on the Mechanism of Shisiwei Jianzhong Decoction in Treating Non-severe Aplastic Anemia with Kidney Yang Deficiency Based on the C Vactivated T Nuclear Factor(NFATc4)(2020ZB086)Zhejiang Province Traditional Chinese Medicine Science and Technology Youth Talent Plan Project:Study on the Academic thought and Clinical Application of Professor Zhou Yuhong in the Treatment of Chronic Aplastic Anemia(2021ZQ029)。
文摘OBJECTIVE:To investigate the effect of Shisiwei Jianzhong decoction(十四味建中汤,SJD)on non-severe aplastic anemia(NSAA).METHODS:Bone marrow mesenchymal stem cells(BMSCs)were isolated from bone marrow samples of 15 NSAA patients and 3 healthy controls.Cells were treated with gradient concentrations of SJD,and a portion was transfected with a vector overexpressing the nuclear factor of activated T cells,cytoplasmic 4(NFATC4).Cell viability and apoptosis were detected by cell counting kit-8 and flow cytometry,respectively.After adipogenic differentiation induction,lipid droplet formation in BMSCs was examined by Oil Red O staining.The expression of NFATC4,peroxisome proliferator-activated receptor gamma(PPARG),fatty acid-binding protein 4(FABP4),peroxisome proliferator-activated receptor-gamma coactivator(PGC-1α),and acetylated PGC-1αwas measured by quantitative real-time polymerase chain reaction or Western blot.RESULTS:SJD significantly increased the viability and decreased the apoptosis of NSAA-derived BMSCs.It also dose-dependently inhibited lipid droplet formation and decreased the expression of PPARG and FABP4 in NSAA-derived BMSCs.NFATC4 expression was higher in patients with NSAA than in healthy controls,and SJD downregulated its expression.NFATC4 overexpression reversed the inhibitory effect of SJD on adipogenic differentiation.Additionally,SJD promoted the deacetylation of PGC-1αin NSAA-derived BMSCs,which was also partially eliminated by NFATC4 overexpression.CONCLUSIONS:SJD inhibits adipogenic differentiation of BMSCs through downregulating NFATC4,thereby contributing to the remission of NSAA.
文摘To investigate the efficacy of a structured continuous nursing intervention program on clinical outcomes,self-efficacy,and sleep quality in patients diagnosed with aplastic anemia(AA).Methods:This study was a single-center,parallel-group,randomized controlled trial.A total of 64 patients with AA,treated at our hospital’s hematology department from May 2022 to May 2025,were enrolled.Participants were randomly allocated in a 1:1 ratio to either the control group(n=32),receiving routine nursing care,or the intervention group(n=32),receiving a six-month continuous nursing intervention program in addition to routine care.The intervention program consisted of structured health education,individualized psychological support,regular telephone follow-ups,and a 24/7 online communication platform.The primary outcome was the change in the Pittsburgh Sleep Quality Index(PSQI)score from baseline to six months.Secondary outcomes included hematological parameters(hemoglobin[Hb],absolute neutrophil count[ANC],platelet count[PLT]),incidence of adverse events(infections,bleeding episodes),quality of life(assessed by the Functional Assessment of Cancer Therapy–Anemia[FACT-An]),and self-efficacy(assessed by the General Self-Efficacy Scale[GSE]).Statistical analyses were performed using independent t-tests,and chi-square tests or Fisher’s exact tests as appropriate.Results:A total of 55 patients(28 in the intervention group and 27 in the control group)completed the study.At baseline,there were no statistically significant differences in demographic data,clinical characteristics,or outcome measures between the two groups(p>0.05).After six months,the mean PSQI score in the intervention group was significantly lower than that in the control group(7.12±2.05 vs.13.49±2.88;t=−13.450;p<0.001).The intervention group also demonstrated a significantly lower incidence of infections(4/28,14.29%vs.10/27,37.04%;p=0.048)and bleeding episodes requiring intervention(3/28,10.71%vs.9/27,33.33%;p=0.042).Furthermore,patients in the intervention group reported significantly higher scores on the FACT-An(125.70±10.31 vs.109.44±12.10;t=7.934;p<0.001)and the GSE scale(29.82±4.11 vs.23.51±4.80;t=7.311;p<0.001).While hematological parameters showed a trend toward improvement in the intervention group,the differences were not statistically significant compared to the control group(p>0.05).Conclusion:The implementation of a structured continuous nursing intervention program can significantly improve sleep quality,reduce the incidence of complications,and enhance quality of life and self-efficacy in patients with aplastic anemia.This evidence-based model of care should be considered for integration into standard clinical practice for the long-term management of this patient population.
基金Supported by Hangzhou Municipal Bureau of Science and Technology,No.2021WJCY366.
文摘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.
文摘Aplastic anemia(AA)is a rare but serious condition in which the bone marrow fails to produce sufficient new blood cells,leading to fatigue,increased susceptibility to infection,and uncontrolled bleeding.In this editorial,we review and comment on an article by Wang et al published in 2024.This study aimed to evaluate the potential therapeutic benefits of ginsenoside Rg1 in AA,focusing on its protective effects and uncovering the underlying mechanisms.Cyclophosphamide(CTX)administration caused substantial damage to the structural integrity of the bone marrow and decreased the number of hematopoietic stem cells,thereby establishing an AA model.Compared with the AA group,ginsenoside Rg1 alleviated the effects of CTX by reducing apoptosis and inflammatory factors.Mechanistically,treatment with ginsenoside Rg1 significantly mitigated myelosuppression in mice by inhibiting the mitogen activated protein kinase signaling pathway.Thus,this study indicates that ginsenoside Rg1 could be effective in treating AA by reducing myelosuppression,primarily through its influence on the mitogen activated protein kinase signaling pathway.We expect that our review and comments will provide valuable insights for the scientific community related to this research and enhance the overall clarity of this article.
文摘Aplastic anemia (AA) is a rare, life-threatening disease characterized by pancytopenia and bone marrow failure. However, since the introduction of immunosuppressive therapy and allogeneic stem cell transplantation, outcomes have improved considerably, with 5-year survival reported to be 70% - 90%. In Congo, contemporary data on survival are lacking. We performed a retrospective study to describe the epidemiological, diagnostic, and therapeutic characteristics of patients with AA diagnosed in the clinical hematology department of the University Hospital of Brazzaville from 2017 to 2023. Chemically induced aplasia was excluded from the study. The CAMITTA criteria were used to classify the severity of AA. In total, 45 confirmed cases were identified, and 35 files provided sufficient data for the descriptive study. The median age was 26 years (range: 1 - 50). Adults made up 75% of the study population. The sex ratio was 1.05 (0.5 in children and 1.17 in adults). One case of AA was secondary to treatment with imatinib mesylate;the other cases (97.1%) were idiopathic. Pancytopenia was present in all patients. Moderate, severe, and very severe AA represented 11.4%, 74.3%, and 14.3% of cases, respectively. Severe and very severe forms were more frequent in adults (77.4% vs. 22.6%) and in men. Nine patients (26%) received cyclosporine monotherapy. Only one received treatment regularly and obtained the only favorable response. No patient received ATG or eltrombopag. Hemorrhagic syndrome was the most common cause of death (4 out of 6 cases) due to the unavailability of platelet concentrates. Eighteen patients (51.4% of cases) were lost to follow-up. The median follow-up was 28.7 (1 - 96) months. In conclusion, the prognosis of AA remains poor and could be improved with affordable immunosuppressive treatments, availability of platelet concentrates, and implementation of allogeneic bone marrow transplantation.
文摘Objective:To explore the difference of lymphocyte subsets in peripheral blood(PB)between aplastic anemia(AA)and hypoplastic myelodysplastic syndrome(hypo-MDS)patients,meanwhile to compare the clinical parameters obtained from PB and bone marrow(BM).Methods:The lymphocyte subsets in hypo-MDS(n=25)and.AA(n=33)patients were investigated by flow cytometry.Meanwhile,the differences in PB cell counts,biochemical indicators,BM cell counts and abnormal chromosomes between the two groups were analyzed.Results:The percentage of CD8^(+)T cells in AA group was significantly higher than that in hypo-MDS group(P=0.001),while the percentage of CD4^(+)T cells and the CD4^(+)/CD8^(+)ratio in AA group were obviously lower than those in hypo-MDS group(P=0.015 and 0.001,respectively).Furthermore,the proportion of CD4^(+)and CD8^(+)activated T(TA)cells,and memory Tregs in AA group was distinctly lower than those in hypo-MDS group(P=0.043,0.015 and 0.024,respectively).Nevertheless,the percentage of CD8^(+)naive T(TN)cells in AA patients was remarkably higher(P=0.044).And hypo-MDS patients had declined lymphocyte counts(P=0.025),increased levels of total bilirubin(TBil),lactate dehydrogenase(LDH),vitamin B12 and proportion of BM blasts than AA patients(P=0.019,0.023,0.027 and.0.045,respectively).Conclusion:In this study it was confirmed that the percentages of CD4^(+)and CD8^(+)TA cells,memory Tregs and CD8^(+)TN cells were significantly different between AA and hypo-MDS patients,which provide an essential basis for the identification of these two diseases.
基金(in part)Instituto de Salud Carlos III(PI11/01907),Ministerio de Economia y Competitividad,co-funded by Fondo Europeo de Desarrollo Regional,Union Europea,Una manera de hacer EuropaRoche Organ Transplantation Research Foundation(ROTRF,CI:442035057)(all to Forns X)
文摘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.
基金Supported by National Center for Advancing Translational Sciences,National Institutes of Health,through Grant Nos.UL1TR001436 and 1TL1TR001437(to Broglie L)MACC Fund(to Margolis D and Medin JA)
文摘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.
基金supported by the Specialized Research Fund for the Doctoral Program of Higher Education of China(No.200804871044)
文摘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...
文摘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.
文摘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.
文摘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.
文摘We previously reported a serendipitous finding from a patient with refractory severe aplastic anemia who had gotten an unexpected hematological response to treatment with gut-cleansing preparations(GCPs).This patient experienced three recurrences over the ensuing one year of intermittent GCP treatments,with each recurrence occurring 7-8 wk from a GCP.After his third recurrence,he was prescribed successive treatment with rifampicin,berberine,and monthly administered GCP for 4 mo,and he developed an erythroid proliferative neoplasma and an overwhelming enteropathy,and eventually died of septic shock.Laboratory investigations had validated the resolution of myelosuppression and the appearance of malignant clonal hematopoiesis.From the treatment process and laboratory investigations,it is reasonably inferred that the engagement of gut inflammation is critically required in sustaining the overall pathophysiology of acquired aplastic anemia probably by creating a chronic inflammatory state.Incorporation of rifampicin,berberine,and monthly GCP into cyclosporine can enhance the immunosuppressive effect.In a subgroup of acquired aplastic anemia patients whose pathogenesis is associated with genotoxic exposure,the suppressed normal hematopoiesis may result from the bystander insult that is mediated by the soluble inflammatory cytokines generated in response to the immunogenic products of damaged hematopoietic cells in the context of chronic inflammatory state and may offer a protective antineoplastic mechanism against malignant proliferation.
基金Supported by the project from Provincial Science and Technology Department,No.2019SC0012。
文摘BACKGROUND Aplastic anemia(AA)complicated with myocardial infarction(MI)is rare and associated with poor prognosis.Here,we present a case of AA with recurrent acute MI(AMI)in a patient treated with cyclosporine A(CsA)and stanozolol.In this patient,we suspect the long-term use of medication linked to platelets hyperfunction.CASE SUMMARY In 2017,a 45-year-old man was rushed to the emergency department of China-Japan Union Hospital due to precordial pain for 5 h.Based on his symptoms,medical history,blood tests,and findings from coronary angiography(CAG),the patient was diagnosed with acute anterior wall,ST-segment elevated MI,Killip II grade,AA,and dyslipidemia.In 2021,the patient was readmitted to the hospital for 2 h due to chest pain.Because the patient’s platelet count was 30×109/L and he had severe thrombocytopenia,we performed CAG following platelet transfusion.Optical coherence tomography revealed lipid plaque and thrombus mass in his right coronary artery.The antithrombotic approach was adjusted to employ only anticoagulants(factor Xa inhibitors)and adenosine diphosphate inhibitors(clopidogrel)after assessing the risk of bleeding/thrombotic events.Long-term follow-up revealed that the patient had made a good recovery.CONCLUSION Patients with AA should be closely monitored for the risk of thrombosis and cardiovascularevents, particularly when taking stanozolol or CsA for an extended period of time.
文摘BACKGROUND Hepatitis-associated aplastic anemia(HAAA) is a rare condition. Patients with HAAA usually present with acute hepatitis, jaundice and significantly increased transaminase. After 1–2 mo, hepatitis gradually improves, but progressive hemocytopenia, bone marrow hematopoietic failure, and severe or extremely severe aplastic anemia are manifest. Most cases of HAAA are fulminant and usually lethal if left untreated. The literature on Epstein–Barr virus(EBV)-associated HAAA is sparse.CASE SUMMARY We report a 30-year-old man who was admitted to our hospital because of pale yellow urine and skin with a simultaneous decrease in peripheral blood ternary cells. We made a diagnosis of EBV-associated HAAA. The treatment strategy for this patient included eltrombopag, an immunosuppressive regimen of rabbit antihuman thymocyte immunoglobulin, cyclosporine, and supportive care. The patient was discharged in normal physical condition after five months. A hemogram performed on follow-up revealed that he had achieved a complete response.CONCLUSION Eltrombopag plus anti-thymocyte globubin and cyclosporine may be a therapeutic option for EBV-associated HAAA.Larger studies are warranted to confirm.
基金This study was supported by the Starting Fund for Returned Scholars of PLA (No. 947008).
文摘Objective. To explore the relationship between human parvovirus B19 (HPV B19) infection and aplastic anemia (AA) and to investigate the role of HPV B19 in the occurrence of AA. Methods. The presence of HPV B19 DNA was detected in the peripheral blood samples of 60 patients with AA (children 38 and adults 22) by nested polymerase chain reaction (PCR) assay, and 30 healthy persons were selected as control. Results. Sixteen (26.7％ ) of 60 AA cases were HPV B19 DNA positive, while all the samples in the control group were negative for HPV B19 (P = 0.000914). Among the case group, the positive rates of HPV B19 DNA were 21.4％ (6 / 28), 30.0％ (3 / 10), 20.0％ (1 / 5) and 35.3％ (6 / 17) in children acute AA (AAA), children chronic AA (CAA), adults AAA and adults CAA patients respectively, which were significantly higher than that in the control group. Furthermore, there was no remarkable difference between children AA and adults AA in the 16 HPV B19 DNA positive patients; neither was there between AAA and CAA. Conclusions. HPV B19 infection is not only correlated with the occurrence of children AAA and CAA, but also with adults AAA and CAA, and might be an important viral cause for AA in humans.
基金ThisprojectwassupportedbyagrantfromNationalNaturalSciencesFoundationofChina (No .30 0 70 32 6 ) .
文摘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.
基金funding support from the Natural Science Foundation of China(No.81673585,No.81874493,No.81573956)Program of Survey of Chinese Medicines of China(No.[2017]66)+5 种基金Science Foundation of Hunan Province(No.2019JJ50345,No.2020JJ5325,No.2021168)Key Research and Development Project of Changsha Science and Technology(No.kq1901067)Training Program for Excellent Young Innovators of Changsha(No.kq1802017)Research on the Comprehensive Development and Utilization of Characteristic Traditional Chinese Medicine Resources(No.2060302)the Support of Hunan Province Traditional Chinese Medicine Preparation and Quality Traceability Engineering and Technology Centerthe 2011 Collaboration and Innovation Center for Digital Chinese Medicine in Hunan。
文摘Objective To elucidate the mechanisms underlying the therapeutic effects of Fufang Ejiao Jiang(复方阿胶浆,FFEJJ)on aplastic anemia(AA)using integrated network pharmacology and serum metabolomics.Methods Traditional Chinese Medicine Systems Pharmacology(TCMSP),Pubmed,integrative pharmacology-based research platform of traditional Chinese medicine(TCMIP),and Bioinformatics Analysis Tool for Molecular mech ANism of Traditional Chinese Medicine(BATMAN-TCM)were used to identify the constituents and putative targets of FFEJJ.Gene Cards and DisGeNET databases were used to identify AA-associated targets.We constructed a herb-component-target network and analyzed the protein-protein interaction(PPI)network.Potential mechanisms were determined using Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analyses.In addition,an AA model was established using acetylphenylhydrazine(APH)and cetylphenylhydrazine(CTX).Ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UPLC-QTOF/MS)-based serum metabolomics was applied to screen potential metabolites and the related pathways associated with AA and the potential anti-anemic effects of FFEJJ.Results A total of 30 active components of FFEJJ and 24 targets were related to AA.PPI network analysis showed that VEGFA,AKT1,IL-6,CASP3,and ICAM1 were key nodes overlapping with proteins known to be related to AA.KEGG pathway enrichment analysis revealed that the presumed targets of FFEJJ were mainly associated with pathways linked to the promotion of hematopoiesis and improvement of the hematopoietic microenvironment.A total of 423 metabolite biomarkers were identified between the control and AA models,which are involved in the development of AA.In contrast,FFEJJ reversed the 79 differential metabolites altered by AA.Pathway analysis suggested that the synergistic effects of FFEJJ were mainly enriched in 24 metabolic pathways.Among them,sphingolipid metabolism,glycerophospholipid metabolism,and arachidonic acid metabolism were related to promoting hematopoiesis and improving the hematopoietic microenvironment,which partially conforms with network pharmacology.The interaction network formed by three key differential metabolites,including hydroxy-eicosatetraenoic acid(HETE),sphingosine 1-phosphate(S1 P),and lysophosphatidylcholine(lyso PC),and three predicted network targets(VEGFA,CASP3,and ICAM1)may be the potential mechanism underlying the anti-AA action of the multi-component of FFEJJ.Conclusion FFEJJ could be an alternative treatment option for AA.It acts by promoting hematopoiesis and improving the hematopoietic microenvironment.Network pharmacology-integrated metabolomics makes it possible to analyze TCMs from a systems perspective and at the molecular level.
