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;p0.05).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
OBJECTIVE: To explore the effect of kidney-rein- forcing, blood-activating and stasis-removing recipes on adhesion molecule expression of bone mar- row mesenchymal stem cells (MSCs) from patients with chronic aplas...OBJECTIVE: To explore the effect of kidney-rein- forcing, blood-activating and stasis-removing recipes on adhesion molecule expression of bone mar- row mesenchymal stem cells (MSCs) from patients with chronic aplastic anemia (CAA). METHODS: We used three Traditional Chinese Medicine recipes, namely a kidney-reinforcing recipe (KRR), blood-activating and stasis-removing recipe (BASRR), and kidney-reinforcing, blood-activating and stasis-removing recipe (KRBASFIR), and a nor- mal saline control to prepare herbal medicine se- rum in Sprague Dawley rats. Thirty CAA patients were enrolled in the experimental group, including 17 kidney-Yang deficient patients and 13 kidney-Yin deficient patients. Ten healthy individuals were included in the control group. MSCs were isolated from bone marrow samples, and the cell density was observed to measure their proliferation ability by microscopy on days 2, 7, and 14 after isolation. In addition, the expression of adhesion molecules of bone marrow MSCs (CD106, CD49d, CD31 and CD44) were detected by flow cytometry after 48 h of treatment with the four different herbal medi- cine serums. RESULTS: The proliferation of MSCs from kid- ney-Yang deficient and kidney-Yin deficient pa- tients was weaker than that of MSCs from the con- trol group. The expression of all adhesion mole- cules of bone marrow MSCs from CAA patients was obviously lower than that in the control group (P〈 0.01). The expression of CD49d and CD31 in MSCs from patients with a kidney-Yin deficiency was low- er than in those with a kidney-yang deficiency (P〈 0.05 and P〈O.01, respectively). For kidney-Yang defi- cient patients, CD31 expression in the KRBASRR group was significantly higher than that in the BASRR group (P〈O.01), while CD44 in the KRBASRR group was significantly higher than that in both KRR and BASRR groups (P〈O.01). For kidney-Yin defi- cient patients, CD106 and CD49d expression in the KRBASRR group was obviously higher than that in the KRR group (P〈0.05), while CD31 and CD44 ex- pression in the KRBASRR group was significantly higher than that in both KRR and BASRR groups (P〈 0.05 and P〈0.01, respectively). CONCLUSION: The bone marrow microenviron- ment in CAA patients is abnormal. The effect of KRBASRR may be better than that of KRR and BASRR for kidney-Yang deficient and kidney-Yin de- ficient patients by improving the expression levels of MSC adhesion molecules.展开更多
OBJECTIVE:To compare the efficacy of modified treatments based on"kidney reinforcing"in the management of chronic aplastic anemia(CAA),and explore their advantages and specialties.METHODS:One hundred and ele...OBJECTIVE:To compare the efficacy of modified treatments based on"kidney reinforcing"in the management of chronic aplastic anemia(CAA),and explore their advantages and specialties.METHODS:One hundred and eleven patients with CAA were randomly divided into three groups:kidney reinforcing alone(KA),"kidney reinforcing and Qi tonifying"(KQ),and"kidney reinforcing and blood circulation invigorating"(KC).Normal and positive control groups were also formed.All patients were treated for 6 months(two courses).Hemograms,Traditional Chinese Medicine(TCM)syndrome scores,and therapeutic effects were assessed,and changes in T-lymphocyte subsets,regulatory T cells and cytokines were detected.RESULTS:The KQ and KC groups had lower TCM syndrome scores than the positive control group after 6 months(P<0.05).The KQ group had a higher overall efficacy than the positive control group after 3 months(P<0.05),while platelet counts increased in the KC group after 6 months(P<0.05).CD3+T-lymphocyte ratios decreased only in the KQ group,while CD3+CD4+CD8-Tlymphocytes increased only in the KC group after 6 months(P<0.05).Levels of interferon-γ,tumor necrosis fac-tor-α,interleukin(IL)-2 and IL-6 decreased and levels of IL-4 and IL-10 increased in all treated groups after 6 months.Levels of IL-6 in the KQ and KC groups were lower than those in the positive control group(P<0.05).CONCLUSION:Treatments based on kidney reinforcing have a rebalancing effect on cytotoxic and T helper cells,and regulate expression of interferon-γ,IL-2,IL-6 and IL-4.KQ may be more effective in treating CAA,and KC may have an advantage in platelet recovery.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
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
OBJECTIVE: To explore the effect of antithymocyte globulin (ATG)/antilymphocyte globulin (ALG) plus kidney-nourishing Chinese medicinal (KNCM) on se- vere aplastic anemia (SAA). METHODS: Twenty-five subjects...OBJECTIVE: To explore the effect of antithymocyte globulin (ATG)/antilymphocyte globulin (ALG) plus kidney-nourishing Chinese medicinal (KNCM) on se- vere aplastic anemia (SAA). METHODS: Twenty-five subjects of severe aplastic anemia were treated with ATG/ALD plus KNCM be- tween 1992 and 2009, and the clinical data before and after treatment were collected and analyzed. RESULTS: Of the 25 patients, 9 were nearly cured, 6 were improved, 5 were in remission, and 5 failed. The overall effective rate was 80.0%. The 3-year, 5-year, 10-year, 15-year survival rate were respec- tively 98.6%, 97.3%, 97.3%, 67.5%, and median sur- vival time was 180 months. Compared to the condi- tions before administering the medication of ATG/ ALG plus KNCM, after 2 weeks, reticulocyte was first improved (P=0.001), one month later, followed by palette (P=0.037), two months later, by neutrophil cell in peripheral blood (P=0.001); three months lat- er, then by the hemoglobin (P=0.012). By conduct- ing 1-year follow-up, 1 case of complication--parox-ysmal nocturnal hemoglobinuria (PNH) was identi- fied and the patient still alive today. CONCLUSION: ATG/ALG fect on SAA and could rate. plus KNCM had better ef- improve patients' survival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 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...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.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
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
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
Objective: To observe the effect of Busui Shengxue Granule (补髓生血颗粒Herbal granule for replenishing marrow to produce blood) on chronic aplastic anemia (CAA) patients’ integrin α 6 (VLA-6/CD49f) and laminin (Ln)...Objective: To observe the effect of Busui Shengxue Granule (补髓生血颗粒Herbal granule for replenishing marrow to produce blood) on chronic aplastic anemia (CAA) patients’ integrin α 6 (VLA-6/CD49f) and laminin (Ln). Methods: Sixty-five patients were divided into experimental group and control group through random number table. There were 34 patients, 17 were male and 17 female, aged 2–67, with a medianage of 30.2 ± 8.6, in the experimental group, including 17 patients of kidney-yin deficiency and 17 of kidney-yang deficiency, treated by Busui Shengxue Granule. There were 31 patients in the control group,16 were male and 15 female, aged 4–65, with a medianage of 31.2 ± 8.0; administered Zaizhang Shengxue Tablet (再障生血片Herbal tablet for chronic aplastic anemia). Both groups were treated for six months and compared with 10 normal persons after the treatment. Flow cytometry was adopted to detect the change in the expression of VLA-6/CD49f, receptor in mononuclear cells of CAA patients and normal persons. Enzyme-linked immunosorbent assay was applied to detect the expression of peripheral serum Ln. Results: CAA patients’ VLA-6/CD49f was in the state of low expression and Ln in the state of high expression. After the treatment, both VLA-6/CD49f and Ln were regulated to some extent and the change in the experimental group was better than that of the control group. Compared with the kidney-yin deficiency patients, those indices of kidney-yang deficiency patients were easier to correct. Conclusion: The VLA-6/CD49f and Ln expressions of CAA patients are abnormal. The treatment with Busui Shengxue Granule makes both of them improved.展开更多
BACKGROUND Myelodysplastic syndrome(MDS)is caused by malignant proliferation and ineffective hematopoiesis.Oncogenic somatic mutations and increased apoptosis,necroptosis and pyroptosis lead to the accumulation of ear...BACKGROUND Myelodysplastic syndrome(MDS)is caused by malignant proliferation and ineffective hematopoiesis.Oncogenic somatic mutations and increased apoptosis,necroptosis and pyroptosis lead to the accumulation of earlier hematopoietic progenitors and impaired productivity of mature blood cells.An increased percentage of myeloblasts and the presence of unfavorable somatic mutations are signs of leukemic hematopoiesis and indicators of entrance into an advanced stage.Bone marrow cellularity and myeloblasts usually increase with disease progression.However,aplastic crisis occasionally occurs in advanced MDS.CASE SUMMARY A 72-year-old male patient was definitively diagnosed with MDS with excess blasts-1(MDS-EB-1)based on an increase in the percentages of myeloblasts and cluster of differentiation(CD)34+hematopoietic progenitors and the identification of myeloid neoplasm-associated somatic mutations in bone marrow samples.The patient was treated with hypomethylation therapy and was able to maintain a steady disease state for 2 years.In the treatment process,the advanced MDS patient experienced an episode of progressive pancytopenia and bone marrow aplasia.During the aplastic crisis,the bone marrow was infiltrated with sparsely distributed atypical lymphocytes.Surprisingly,the leukemic cells disappeared.Immunological analysis revealed that the atypical lymphocytes expressed a high frequency of CD3,CD5,CD8,CD16,CD56 and CD57,suggesting the activation of autoimmune cytotoxic T-lymphocytes and natural killer(NK)/NKT cells that suppressed both normal and leukemic hematopoiesis.Elevated serum levels of inflammatory cytokines,including interleukin(IL)-6,interferon-gamma(IFN-γ)and tumor necrosis factor-alpha(TNF-α),confirmed the deranged type I immune responses.This morphological and immunological signature led to the diagnosis of severe aplastic anemia secondary to large granule lymphocyte leukemia.Disseminated tuberculosis was suspected upon radiological examinations in the search for an inflammatory niche.Antituberculosis treatment led to reversion of the aplastic crisis,disappearance of the atypical lymphocytes,increased marrow cellularity and 2 mo of hematological remission,providing strong evidence that disseminated tuberculosis was responsible for the development of the aplastic crisis,the regression of leukemic cells and the activation of CD56+atypical lymphocytes.Reinstitution of hypomethylation therapy in the following 19 mo allowed the patient to maintain a steady disease state.However,the patient transformed the disease phenotype into acute myeloid leukemia and eventually died of disease progression and an overwhelming infectious episode.CONCLUSION Disseminated tuberculosis can induce CD56+lymphocyte infiltration in the bone marrow and in turn suppress both normal and leukemic hematopoiesis,resulting in the development of aplastic crisis and leukemic cell regression.展开更多
Distinguishing between aplastic anemia(AA)and hypoblastic myelodysplastic syndrome(hMDS)with a low percentage of bone marrow(BM)blasts(<5%)can be difficult due to the overlap in clonality and a spectrum of genetic ...Distinguishing between aplastic anemia(AA)and hypoblastic myelodysplastic syndrome(hMDS)with a low percentage of bone marrow(BM)blasts(<5%)can be difficult due to the overlap in clonality and a spectrum of genetic alternations between the two subtypes of diseases.However,due to recent advances in DNA sequencing technology,both spectnim and frequency of mutations can be accurately determined and monitored by next-generation sequencing(NGS)at initial diagnosis and during immunosuppressive therapy(1ST)in patients with AA or hMDS.This improvement in acquiring a patient's genetic status and clonal evolution can provide more proper,precise,and on-time information to guide disease management,which is especially helpful in the absence of traditional morphologic/cytogenetic evidence.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
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
摘要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。
摘要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)。
摘要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.
摘要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;p0.05).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 2011 Zhejiang province key science and technology innovation team(No.2011R09042-02)Special Item of Important Disease of Zhejiang Province TCM Sci-Tech Innovation Platform(No.2009ZDJB01,2009ZDJB01-08)
摘要OBJECTIVE: To explore the effect of kidney-rein- forcing, blood-activating and stasis-removing recipes on adhesion molecule expression of bone mar- row mesenchymal stem cells (MSCs) from patients with chronic aplastic anemia (CAA). METHODS: We used three Traditional Chinese Medicine recipes, namely a kidney-reinforcing recipe (KRR), blood-activating and stasis-removing recipe (BASRR), and kidney-reinforcing, blood-activating and stasis-removing recipe (KRBASFIR), and a nor- mal saline control to prepare herbal medicine se- rum in Sprague Dawley rats. Thirty CAA patients were enrolled in the experimental group, including 17 kidney-Yang deficient patients and 13 kidney-Yin deficient patients. Ten healthy individuals were included in the control group. MSCs were isolated from bone marrow samples, and the cell density was observed to measure their proliferation ability by microscopy on days 2, 7, and 14 after isolation. In addition, the expression of adhesion molecules of bone marrow MSCs (CD106, CD49d, CD31 and CD44) were detected by flow cytometry after 48 h of treatment with the four different herbal medi- cine serums. RESULTS: The proliferation of MSCs from kid- ney-Yang deficient and kidney-Yin deficient pa- tients was weaker than that of MSCs from the con- trol group. The expression of all adhesion mole- cules of bone marrow MSCs from CAA patients was obviously lower than that in the control group (P〈 0.01). The expression of CD49d and CD31 in MSCs from patients with a kidney-Yin deficiency was low- er than in those with a kidney-yang deficiency (P〈 0.05 and P〈O.01, respectively). For kidney-Yang defi- cient patients, CD31 expression in the KRBASRR group was significantly higher than that in the BASRR group (P〈O.01), while CD44 in the KRBASRR group was significantly higher than that in both KRR and BASRR groups (P〈O.01). For kidney-Yin defi- cient patients, CD106 and CD49d expression in the KRBASRR group was obviously higher than that in the KRR group (P〈0.05), while CD31 and CD44 ex- pression in the KRBASRR group was significantly higher than that in both KRR and BASRR groups (P〈 0.05 and P〈0.01, respectively). CONCLUSION: The bone marrow microenviron- ment in CAA patients is abnormal. The effect of KRBASRR may be better than that of KRR and BASRR for kidney-Yang deficient and kidney-Yin de- ficient patients by improving the expression levels of MSC adhesion molecules.
基金Supported by Special Item of Important Disease of Zhejiang Province Traditional Chinese Medicine Sic-Tech Innovation Platform(Effect and Mechanism of Traditional Chinese Medicine on the Treatment of Aplastic Anemia and the Funding of Traditional Chinese Medicine Assessment Criterion,No.2009ZDJB01)Subject of Key Sic-Tech Innovation Team of Zhejiang Province(Clinical Study on Treatment of Chronic Aplastic Anemia by Tonifying Kidney and Promoting Blood Circulation,No.2011R09042-02)+2 种基金Special Research Funds for Traditional Chinese Medicine Industry(Effect of Traditional Chinese Medicine on the Treatment of Risk Factors of Chronic Aplastic Anemia,No.201107001)Special Research Funds for Traditional Chinese Medicine Industry(Clinical Study on the Diagnosis and Treatment of Aplastic Anemia Based on the Syndrome And Stage Differentiation,No.201407001)Zhejiang Provincial Traditional Chinese Medicine Administration Bureau Program(Establishment of Traditional Chinese Medicine Clinical Pathway on Aplastic Anemia,No.2010ZA039)
摘要OBJECTIVE:To compare the efficacy of modified treatments based on"kidney reinforcing"in the management of chronic aplastic anemia(CAA),and explore their advantages and specialties.METHODS:One hundred and eleven patients with CAA were randomly divided into three groups:kidney reinforcing alone(KA),"kidney reinforcing and Qi tonifying"(KQ),and"kidney reinforcing and blood circulation invigorating"(KC).Normal and positive control groups were also formed.All patients were treated for 6 months(two courses).Hemograms,Traditional Chinese Medicine(TCM)syndrome scores,and therapeutic effects were assessed,and changes in T-lymphocyte subsets,regulatory T cells and cytokines were detected.RESULTS:The KQ and KC groups had lower TCM syndrome scores than the positive control group after 6 months(P<0.05).The KQ group had a higher overall efficacy than the positive control group after 3 months(P<0.05),while platelet counts increased in the KC group after 6 months(P<0.05).CD3+T-lymphocyte ratios decreased only in the KQ group,while CD3+CD4+CD8-Tlymphocytes increased only in the KC group after 6 months(P<0.05).Levels of interferon-γ,tumor necrosis fac-tor-α,interleukin(IL)-2 and IL-6 decreased and levels of IL-4 and IL-10 increased in all treated groups after 6 months.Levels of IL-6 in the KQ and KC groups were lower than those in the positive control group(P<0.05).CONCLUSION:Treatments based on kidney reinforcing have a rebalancing effect on cytotoxic and T helper cells,and regulate expression of interferon-γ,IL-2,IL-6 and IL-4.KQ may be more effective in treating CAA,and KC may have an advantage in platelet recovery.
摘要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.
摘要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)
摘要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.
摘要OBJECTIVE: To explore the effect of antithymocyte globulin (ATG)/antilymphocyte globulin (ALG) plus kidney-nourishing Chinese medicinal (KNCM) on se- vere aplastic anemia (SAA). METHODS: Twenty-five subjects of severe aplastic anemia were treated with ATG/ALD plus KNCM be- tween 1992 and 2009, and the clinical data before and after treatment were collected and analyzed. RESULTS: Of the 25 patients, 9 were nearly cured, 6 were improved, 5 were in remission, and 5 failed. The overall effective rate was 80.0%. The 3-year, 5-year, 10-year, 15-year survival rate were respec- tively 98.6%, 97.3%, 97.3%, 67.5%, and median sur- vival time was 180 months. Compared to the condi- tions before administering the medication of ATG/ ALG plus KNCM, after 2 weeks, reticulocyte was first improved (P=0.001), one month later, followed by palette (P=0.037), two months later, by neutrophil cell in peripheral blood (P=0.001); three months lat- er, then by the hemoglobin (P=0.012). By conduct- ing 1-year follow-up, 1 case of complication--parox-ysmal nocturnal hemoglobinuria (PNH) was identi- fied and the patient still alive today. CONCLUSION: ATG/ALG fect on SAA and could rate. plus KNCM had better ef- improve patients' survival
摘要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 Specialized Scientific Research Fund Projects of the Medical Group of Qingdao University,No.YLJT20201002。
摘要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.
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。
摘要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.
摘要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)
摘要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 the National Natural Science Foundation of China (No.90709039)Specialized Research Fund for the Doctoral Program of Higher Education (No.200802280003, No.20092327120001)Heilongjiang Provincial Natural Science Foundation of China (No.D2005-62)
摘要Objective: To observe the effect of Busui Shengxue Granule (补髓生血颗粒Herbal granule for replenishing marrow to produce blood) on chronic aplastic anemia (CAA) patients’ integrin α 6 (VLA-6/CD49f) and laminin (Ln). Methods: Sixty-five patients were divided into experimental group and control group through random number table. There were 34 patients, 17 were male and 17 female, aged 2–67, with a medianage of 30.2 ± 8.6, in the experimental group, including 17 patients of kidney-yin deficiency and 17 of kidney-yang deficiency, treated by Busui Shengxue Granule. There were 31 patients in the control group,16 were male and 15 female, aged 4–65, with a medianage of 31.2 ± 8.0; administered Zaizhang Shengxue Tablet (再障生血片Herbal tablet for chronic aplastic anemia). Both groups were treated for six months and compared with 10 normal persons after the treatment. Flow cytometry was adopted to detect the change in the expression of VLA-6/CD49f, receptor in mononuclear cells of CAA patients and normal persons. Enzyme-linked immunosorbent assay was applied to detect the expression of peripheral serum Ln. Results: CAA patients’ VLA-6/CD49f was in the state of low expression and Ln in the state of high expression. After the treatment, both VLA-6/CD49f and Ln were regulated to some extent and the change in the experimental group was better than that of the control group. Compared with the kidney-yin deficiency patients, those indices of kidney-yang deficiency patients were easier to correct. Conclusion: The VLA-6/CD49f and Ln expressions of CAA patients are abnormal. The treatment with Busui Shengxue Granule makes both of them improved.
基金Supported by The Specialized Scientific Research Fund Projects of The Medical Group of Qingdao University,No.YLJT20201002.
摘要BACKGROUND Myelodysplastic syndrome(MDS)is caused by malignant proliferation and ineffective hematopoiesis.Oncogenic somatic mutations and increased apoptosis,necroptosis and pyroptosis lead to the accumulation of earlier hematopoietic progenitors and impaired productivity of mature blood cells.An increased percentage of myeloblasts and the presence of unfavorable somatic mutations are signs of leukemic hematopoiesis and indicators of entrance into an advanced stage.Bone marrow cellularity and myeloblasts usually increase with disease progression.However,aplastic crisis occasionally occurs in advanced MDS.CASE SUMMARY A 72-year-old male patient was definitively diagnosed with MDS with excess blasts-1(MDS-EB-1)based on an increase in the percentages of myeloblasts and cluster of differentiation(CD)34+hematopoietic progenitors and the identification of myeloid neoplasm-associated somatic mutations in bone marrow samples.The patient was treated with hypomethylation therapy and was able to maintain a steady disease state for 2 years.In the treatment process,the advanced MDS patient experienced an episode of progressive pancytopenia and bone marrow aplasia.During the aplastic crisis,the bone marrow was infiltrated with sparsely distributed atypical lymphocytes.Surprisingly,the leukemic cells disappeared.Immunological analysis revealed that the atypical lymphocytes expressed a high frequency of CD3,CD5,CD8,CD16,CD56 and CD57,suggesting the activation of autoimmune cytotoxic T-lymphocytes and natural killer(NK)/NKT cells that suppressed both normal and leukemic hematopoiesis.Elevated serum levels of inflammatory cytokines,including interleukin(IL)-6,interferon-gamma(IFN-γ)and tumor necrosis factor-alpha(TNF-α),confirmed the deranged type I immune responses.This morphological and immunological signature led to the diagnosis of severe aplastic anemia secondary to large granule lymphocyte leukemia.Disseminated tuberculosis was suspected upon radiological examinations in the search for an inflammatory niche.Antituberculosis treatment led to reversion of the aplastic crisis,disappearance of the atypical lymphocytes,increased marrow cellularity and 2 mo of hematological remission,providing strong evidence that disseminated tuberculosis was responsible for the development of the aplastic crisis,the regression of leukemic cells and the activation of CD56+atypical lymphocytes.Reinstitution of hypomethylation therapy in the following 19 mo allowed the patient to maintain a steady disease state.However,the patient transformed the disease phenotype into acute myeloid leukemia and eventually died of disease progression and an overwhelming infectious episode.CONCLUSION Disseminated tuberculosis can induce CD56+lymphocyte infiltration in the bone marrow and in turn suppress both normal and leukemic hematopoiesis,resulting in the development of aplastic crisis and leukemic cell regression.
基金the National Natural Science Foundation of China(No.81470009).
摘要Distinguishing between aplastic anemia(AA)and hypoblastic myelodysplastic syndrome(hMDS)with a low percentage of bone marrow(BM)blasts(<5%)can be difficult due to the overlap in clonality and a spectrum of genetic alternations between the two subtypes of diseases.However,due to recent advances in DNA sequencing technology,both spectnim and frequency of mutations can be accurately determined and monitored by next-generation sequencing(NGS)at initial diagnosis and during immunosuppressive therapy(1ST)in patients with AA or hMDS.This improvement in acquiring a patient's genetic status and clonal evolution can provide more proper,precise,and on-time information to guide disease management,which is especially helpful in the absence of traditional morphologic/cytogenetic evidence.
摘要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.
基金supported by the Specialized Research Fund for the Doctoral Program of Higher Education of China(No.200804871044)
摘要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...