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Antibiotic and glucocorticoid-induced recapitulated hematological remission in acute myeloid leukemia:A case report and review of literature

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World Journal of Clinical Cases 2022年第22期10卷 7890-7898页

作者： xiao-yun sun xiao-Dong Yang xiao-Qiu Yang Bo Ju Nuan-Nuan Xiu Jia Xu Xi-Chen Zhao Department of Hematology The Central Hospital of Qingdao West Coast New AreaQingdao 266555Shandong ProvinceChina Department of Pharmacology The Central Hospital of Qingdao West Coast New AreaQingdao 266555Shandong ProvinceChina

BACKGROUND Leukemic hematopoietic cells acquire enhanced self-renewal capacity and impaired *** emergence of symptomatic leukemia also requires the acquisition of a clonal proliferative *** leukemia patients usually experience an aggressive ***,spontaneous remission occasionally occurs in patients with acute myeloid leukemia(AML),most frequently after recovery from a febrile episode,and this is generally attributed to the triggering of antineoplastic *** may be another explanation for the spontaneous remission as implicated in this *** SUMMARY A 63-year-old Chinese man presented with high fever,abdominal pain and urticaria-like skin *** was diagnosed with AML-M4 with t(8;21)(q22;q22)/RUNX1-RUNX1T1 based on morphological,immunological,cytogenetic and molecular *** had a complex chromosome rearrangement of 48,XY,t(8;21)(q22;q22),+13,+13[9]/49,idem,+mar[9]/49,idem,+8[2].He also had a mutated tyrosine kinase domain in fms-like tyrosine kinase 3 *** was treated with antibiotics and glucocorticoids for gastrointestinal infection and urticaria-like skin *** infection and skin lesions were quickly ***,he achieved hematological remission along with resolution of the febrile episode,gastrointestinal symptoms and skin ***,after relapse,repeating these treatments resulted in a return to hematological ***,he demonstrated strong resistance to antibiotic and glucocorticoid treatment after the second relapse and died of sepsis from bacterial infection with multidrug *** main clinical feature of this patient was that symptomatic AML emerged with flaring of the gut inflammatory disorder and it subsided after resolution of the *** from the present case raises the possibility that in a subgroup of AML patients,the proliferative advantage of leukemia cells may critically require the presence of inflammatory ***

关键词： Acute myeloid leukemia Fms-like tyrosine kinase 3 tyrosine kinase domain Glucocorticoid Antibiotic Spontaneous remission Gastrointestinal infection Case report

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Acquired aplastic anemia:Is bystander insult to autologous hematopoiesis driven by immune surveillance against malignant cells?

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World Journal of Stem Cells 2020年第11期12卷 1429-1438页

作者： Xi-Chen Zhao xiao-yun sun Bo Ju Fan-Jun Meng Hong-Guo Zhao Department of Hematology The Central Hospital of Qingdao West Coast New AreaQingdao 266555Shandong ProvinceChina Department of Hematology The Affiliated Hospital of Qingdao UniversityQingdao 266000Shandong ProvinceChina

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 *** 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 *** investigations had validated the resolution of myelosuppression and the appearance of malignant clonal *** 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 *** of rifampicin,berberine,and monthly GCP into cyclosporine can enhance the immunosuppressive *** 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.

关键词： Acquired aplastic anemia Bystander insult Malignant clonal hematopoiesis Immune surveillance Antineoplastic Gut inflammation

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Tuberculosis-induced aplastic crisis and atypical lymphocyte expansion in advanced myelodysplastic syndrome:A case report and review of literature

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World Journal of Clinical Cases 2023年第19期11卷 4713-4722页

作者： xiao-yun sun xiao-Dong Yang Jia Xu Nuan-Nuan Xiu Bo Ju Xi-Chen Zhao Department of Hematology The Central Hospital of Qingdao West Coast New AreaQingdao 266555Shandong ProvinceChina

BACKGROUND Myelodysplastic syndrome(MDS)is caused by malignant proliferation and ineffective *** somatic mutations and increased apoptosis,necroptosis and pyroptosis lead to the accumulation of earlier hematopoietic progenitors and impaired productivity of mature blood *** increased percentage of myeloblasts and the presence of unfavorable somatic mutations are signs of leukemic hematopoiesis and indicators of entrance into an advanced *** marrow cellularity and myeloblasts usually increase with disease ***,aplastic crisis occasionally occurs in advanced *** 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 *** patient was treated with hypomethylation therapy and was able to maintain a steady disease state for 2 *** the treatment process,the advanced MDS patient experienced an episode of progressive pancytopenia and bone marrow *** the aplastic crisis,the bone marrow was infiltrated with sparsely distributed atypical ***,the leukemic cells *** 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 *** 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 *** morphological and immunological signature led to the diagnosis of severe aplastic anemia secondary to large granule lymphocyte *** tuberculosis was suspected upon radiological examinations in the s

关键词： Myelodysplastic syndrome Aplastic crisis Atypical lymphocyte Leukemic cell regression CD56+lymphocyte expansion Disseminated tuberculosis Case report

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Flared inflammatory episode transforms advanced myelodysplastic syndrome into aplastic pancytopenia:A case report and literature review

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World Journal of Clinical Cases 2023年第17期11卷 4105-4116页

作者： Bo Ju Nuan-Nuan Xiu Jia Xu xiao-Dong Yang xiao-yun sun Xi-Chen Zhao Department of Hematology The Central Hospital of Qingdao West Coast New AreaQingdao 266555Shandong ProvinceChina

BACKGROUND Myelodysplastic syndrome(MDS)is a hematological neoplasm,and an increase in myeloblasts is representative of leukemic hematopoiesis in advanced *** MDS usually exhibits deranged autoimmunity resembling that of aplastic anemia(AA),whereas advanced MDS is characterized by a phenotype of immune *** can be normo/hyperplastic or ***,bone marrow cellularity and myeloblasts increase with disease *** from advanced MDS to AA-like syndrome with leukemic cell regression has not previously been *** SUMMARY A middle-aged Chinese woman had a 4-year history of *** months prior to admission,the patient developed gradually worsening fatigue and performance *** leukocytopenia further *** was diagnosed with MDS with excess blasts-2 based on increased bone marrow cellularity and an increased percentage of myeloblasts on marrow and blood smears,an increased percentage of cluster of differentiation(CD)34+CD33+progenitors in immunotyping analysis,a normal karyotype in cytogenetic analysis,and the identification of somatic mutations in CBL,KMT2D and NF1 in molecular ***,neutropenia was the predominant hematological abnormality,with mild anemia and thrombocytosis,and the degree of fatigue was far more severe than the degree of *** the following months,the patient experienced several febrile *** antibiotic treatments were able to control the febrile episodes,but the elevated inflammatory indices *** hematological parameters dramatically fluctuated with the waxing and waning of the inflammatory *** recurrent flares of the inflammatory condition,agranulocytosis and severe anemia developed,with mild *** the patient’s hospitalization,computed tomography(CT)scans revealed the presence of extensive inflammatory lesions involving the lungs,mediastinum,pleura,gastrointestinal tract,peritoneum and urinary tract,

关键词： Myelodysplastic syndrome Aplastic anemia Inflammatory stress Leukemic cell regression Antileukemic Case report

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Glucocorticoid-induced thrombotic microangiopathy in paroxysmal nocturnal hemoglobinuria:A case report and review of literature

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World Journal of Clinical Cases 2023年第8期11卷 1799-1807页

作者： xiao-Dong Yang Bo Ju Jia Xu Nuan-Nuan Xiu xiao-yun sun Xi-Chen Zhao Department of Hematology The Central Hospital of Qingdao West Coast New AreaQingdao 266555Shandong ProvinceChina

BACKGROUND Thrombotic microangiopathy(TMA)is a group of disorders that converge on excessive platelet aggregation in the microvasculature,leading to consumptive thrombocytopenia,microangiopathic hemolysis and ischemic end-organ *** predisposed patients,TMA can be triggered by many environmental ***(GCs)can compromise the vascular ***,GC-associated TMA has rarely been reported,which may be due to the lack of awareness of *** the high frequency of thrombocytopenia during GC treatment,particular attention should be given to this potentially fatal *** SUMMARY An elderly Chinese man had a 12-year history of aplastic anemia(AA)and a 3-year history of paroxysmal nocturnal hemoglobinuria(PNH).Three months earlier,methylprednisolone treatment was initiated at 8 mg/d and increased to 20 mg/d to alleviate complement-mediated *** GC treatment,his platelet counts and hemoglobin levels rapidly *** admission to our hospital,the dose of methylprednisolone was increased to 60 mg/d in an attempt to enhance the suppressive ***,increasing the GC dose did not alleviate hemolysis,and his cytopenia *** evaluation of the marrow smears revealed increased cellularity with an increased percentage of erythroid progenitors without evident *** of differentiation(CD)55 and CD59 expression was significantly decreased on erythrocytes and *** the following days,platelet transfusion was required due to severe *** of platelet transfusion refractoriness indicated that the exacerbated cytopenia may have been caused by the development of TMA due to GC treatment because the transfused platelet concentrates had no defects in glycosylphosphatidylinositol-anchored *** examined blood smears and found a small number of schistocytes,dacryocytes,acanthocytes and target *** of GC treatment resulted in rapidl

关键词： Aplastic anemia Paroxysmal nocturnal hemoglobinuria Glucocorticoid Methylprednisolone Thrombotic microangiopathy Platelet transfusion refractoriness Case report

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

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World Journal of Clinical Cases 2023年第28期11卷 6908-6919页

作者： Nuan-Nuan Xiu xiao-Dong Yang Jia Xu Bo Ju xiao-yun sun Xi-Chen Zhao Department of Hematology The Central Hospital of Qingdao West Coast New AreaQingdao 266555Shandong ProvinceChina

BACKGROUND Accumulating evidence demonstrates that autoimmune hematopoietic failure and myeloid neoplasms have an intrinsic relationship with regard to clonal hematopoiesis and disease *** approximately 10%-15%of patients with severe aplastic anemia(SAA),the disease phenotype is transformed into myeloid neoplasms following antithymocyte globulin plus cyclosporine-based immunosuppressive *** some of these patients,myeloid neoplasms appear during or shortly after immunosuppressive *** transformation in SAA patients during anti-tuberculosis treatment has not been *** SUMMARY A middle-aged Chinese female had a 6-year history of non-SAA and a 2-year history of paroxysmal nocturnal hemoglobinuria(PNH).With aggravation of systemic inflammatory symptoms,severe pancytopenia developed,and her hemoglobinuria *** findings in cytological,immunological and cytogenetic analyses of bone marrow samples met the diagnostic criteria for“SAA.”Definitive diagnosis of disseminated tuberculosis was made in the search for infectious *** improvement in hematological parameters was achieved within 1 mo of anti-tuberculosis treatment,and complete hematological remission was achieved within 4 mo of ***,the hematological response lasted for only 3 mo,and pancytopenia *** this time,cytological findings(increased bone marrow cellularity and an increased percentage of myeloblasts that accounted for 16.0%of all nucleated hematopoietic cells),immunological findings(increased percentage of cluster of differentiation 34+cells that accounted for 12.28%of all nucleated hematopoietic cells)and molecular biological findings(identification of somatic mutations in nucleophosmin-1 and casitas B-lineage lymphoma genes)revealed that“SAA”had transformed into acute myeloid leukemia with mutated *** transformation process suggested that the leukemic clones were preexistent but were suppressed in the

关键词： Aplastic anemia Paroxysmal nocturnal hemoglobinuria Acute myeloid leukemia Tuberculosis Leukemic transformation Case report

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Bibliometric analysis of glaucoma-related literature based on SCIE database:a 10-year literature analysis from 2009 to 2018

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International Journal of Ophthalmology(English edition) 2020年第12期13卷 1998-2006页

作者： yun-xiao sun Ying-Na Liu Ying Han Fan-Qi Kong Yue Zhang Siloka Arthur Labisi Kai Cao Beijing Ophthalmology and Visual Sciences Key Laboratory Beijing Tongren Eye CenterBeijing Tongren HospitalCapital Medical UniversityBeijingChina Beijing Institute of Ophthalmology Beijing Tongren HospitalCapital Medical UniversityBeijingChina Department of Ophthalmology University of California San FranciscoSan FranciscoCA 94143USA Allergan plc ShanghaiChina

AIM:To explore the global trends and focus of glaucoma research from 2009 to ***:Searching for glaucoma-related articles published in Science Citation Index Expanded(SCIE)database during 2009-2018,and describing the distribution of the published year,countries,authors,institutions,funding agencies,journals,impact factor,citation and hot research topic of articles by using bibliometric ***,we compared some of these indicators over two five-year periods,from 2009 to 2013 and from 2014 to ***:A total of 19609 glaucoma-related articles were retrieved and the global SCIE articles have increased yearly from 2009 to *** USA was the pioneer which has made great *** kept the second place and the number of publications has increased rapidly between 2014 and *** author with the highest number of publications was Weinreb,***-occurrence maps were built amongst the top 50 authors or the top 50 institutions with the most articles,which visualize the closer collaboration of international authors or *** journal Investigative Ophthalmology&Visual Science has published the most *** literature with an impact factor of 3-5 points accounted for the largest proportion(28.96%).The most frequently cited paper had 798 *** top three hot areas on glaucoma were intraocular pressure,optical coherence tomography(OCT)and retinal ganglion *** trabecular meshwork,primary angle-closure glaucoma and Spectral-domain OCT have become new hot research topics in recent five years during ***:Bibliometric analysis is an effective method to describe the global literature on *** a 10-year literature survey from 2009 to 2018,global glaucoma research has developed in a balanced manner,and the cooperation between various institutions and teams has become ***-related pathogenesis research,imaging examinations of OCT and surgery therapy have attracted most attention.

关键词： bibliometric analysis Science Citation Index Expanded glaucoma ocular hypertension

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

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World Journal of Clinical Cases 2020年第2期8卷 425-435页

作者： Xi-Chen Zhao Li Zhao xiao-yun sun Zeng-Shan Xu Bo Ju Fan-Jun Meng Hong-Guo Zhao Department of Hematology The Central Hospital of Qingdao West Coast New AreaQingdao 266555Shandong ProvinceChina Department of Hematology The Affiliated Hospital of Qingdao UniversityQingdao 266000Shandong ProvinceChina

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 *** 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 *** Chronic gut inflammation may be responsible for AA pathogenesis. The comorbidities and AA may share a common etiological association.

关键词： Case report Severe aplastic anemia Hematological response Chronic gut inflammation Comorbid disease Etiological association

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Gut inflammation in the pathogenesis of acquired aplastic anemia

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Chinese Medical Journal 2020年第15期133卷 1878-1881页

作者： Xi-Chen Zhao xiao-yun sun Li Zhao Fan-Jun Meng Department of Hematology The Central Hospital of Qingdao West Coast New AreaQingdaoShandong 266555China Department of Hematology The Affiliated Hospital of Qingdao UniversityQingdaoShandong 266000China

Acquired aplastic anemia(AAA)is an auto-immune disease(AID)resulting from aberrant T-cell-mediated and antigen-driven immune responses to hematopoietic stem and progenitor cells(HSPCs)in genetically susceptible individuals,leading to the significantly enhanced suppression and apoptosis of *** systemic and local inflammation is responsible for the overall pathophysiology.

关键词： inflammation anemia aplastic

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Comparison of gene expression in cynomolgus monkeys with preclinical type Ⅱ diabetes induced by different high energy diets

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Animal Models and Experimental Medicine 2019年第1期2卷 44-50页

作者： Li-Sha Jin Jun-Hua Rao Li-Biao Zhang Fang Ji Yan-Chun Zhang Xiang-Fen Hao Bai-Lu Peng xiao-Ming Liu yun-xiao sun Guangdong Key Laboratory of Animal Conservation and Resource Utilization Guangdong Public Laboratory of Wild Animal Conservation and UtilizationGuangdong Institute of Applied Biological Resources South China Botanical Garden

Background : Cynomolgus disease models that are similar to the preclinical stage of human type 2 diabetes mellitus(T2 DM) were established by feeding middle-aged cynomolgus monkeys different high energy diets to study the differential expression of diabetes-related genes. Methods : A total of 36 male monkeys were randomly divided into four groups and fed human diets with high sugar, high fat, double high sugar and fat, and a normal diet. The preclinical diabetes phase was determined by monitoring the metabolic characteristic indices and the results of oral glucose tolerance tests( OGTT). The mRNA expression of 45 diabetes-related genes in peripheral blood leukocytes was analyzed using real-time PCR. Results : A total of 22, 25, and 21 genes were significantly up-regulated( P < 0.05) and 5, 7, and 5 genes were significantly down-regulated( P < 0.05) in the above three induced groups, respectively, compared with the control group. Of the 45 tested genes, the expression profiles of 21 genes were consistent. Most of the expression levels in the double high sugar-and-fat individuals were slightly lower than those in the high glucose and high fat groups, although the expression patterns of the three groups were essentially similar. Conclusion : The different high energy diets all induced diabetes and shared some phenotypic properties with human T2 DM. Most of the expression patterns of the related genes were identical. The gene expression profiles could be used as references for the study of early diagnostic indicators and T2 DM pathogenesis.

关键词： cynomolgus monkey gene expression high energy diet preclinical phase type 2 diabetes

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