Objective:To explore blood group serological and molecular biological identification methods of B(A) subtype individuals.Methods:On December 15, 2012 and February 16, 2023, a total of 2 subjects who were sent to Liaocheng Central Blood Station for blood group identification due to difficulty in blood group typing were selected as study subjects. The subject 1 was a 27-year-old female, and subject 2 was a 40-year-old male. The ABO blood group serological identification of subjects was performed by test tube method. PCR-sequence specific primer (SSP) method was used for ABO genotyping of subjects. Exons 6 and 7 of subjects′ ABO gene were sequenced by Sanger sequencing method. Procedure followed in this study was in line with requirements of the World Medical Association Declaration of Helsinki revised in 2013. Results:① The serological phenotype of subject 1 was consistent with AwB or B(A) subtype, and subject 2 was consistent with A 2B or B(A) subtype. ② The ABO gene of subject 1 was heterozygous for B(A)02 and O, with a key nucleotide mutation c.700C>G in exon 7, and her ABO genotype was B(A).02/O.01.01. The ABO gene of subject 2 was heterozygous for B(A)04 and O, with a key nucleotide heterozygous mutation c. 640A>G in exon 7, and his ABO genotype was B(A).04/O.01.01.Conclusions:It is difficult to identify B(A) subtype using only blood group serological tests, and gene sequencing can provide a molecular basis for serological test results.
Objective:To investigate the clinical characteristics, laboratory findings, diagnosis and treatment of patients with central nervous system (CNS)-intravascular lymphoma (IVL), and review the related literature.Methods:On December 19, 2021, a case of a 54 year-old male patient with CNS-IVL admitted to Neurosurgery Department of Chengdu Second People′s Hospital was selected as the study subject. A retrospective analysis method was used to analyze the patient′s clinical data such as medical history, clinical manifestations, laboratory tests, imaging examinations, metagenomic next-generation sequencing (mNGS) results. Diagnose and treatment of this patient based on clinical manifestations and related examination results. China National Knowledge Infrastructure database, Wanfang Data Knowledge Service Platform and PubMed database were searched using " intravascular lymphoma", " diffuse large B-cell lymphoma", " intraspinal hemorrhage", " central nervous system", " spinal cord" as Chinese and English keywords. Diagnosis and treatment data of CNS-IVL involving spinal cord was summarized. The time for literature retrieval was from inception of the database to March 1, 2022. Procedure followed in this study was in line with requirements of the World Medical Association Declaration of Helsinki revised in 2013, and informed consent of clinical research was signed with the patient and his family members. Results:① This patient was admitted due to " numbness and weakness in the left upper limb for 10 d". Previous history of the patient included tuberculous meningitis, viral meningitis, liver dysfunction, severe pneumonia and erythroderma. ② At the time of admission, blood routine test results of this patient showed that white blood cell count (WBC), neutrophil percentage, red blood cell count, hemoglobin (Hb) value, platelet count were 5.4 × 10 9/L, 72.5%, 3.02×10 12/L, 87 g/L, 49 × 10 9/L, respectively. Abdominal color Doppler ultrasound shows mild enlargement of the spleen. Results of cranial MRI, magnetic resonance angiography (MRA), and susceptibility weighted imaging (SWI) showed lacunar cerebral infarction and ischemic focus in the bilateral frontal lobe, left parietal lobe, basal ganglia, and cerebral atrophy, demyelination of white matter. Intracranial artery runs and collateral circulation is normal. A few micro hemorrhage foci were near the right temporal lobe and lateral ventricles. MRI results of spine showed significant swelling of the cervical spinal cord with abnormal signals, indicating consideration of intramedullary hemorrhage. This patient underwent a intramedullary lesion resection, lamina reduction and internal fixation of cervical spine through whole lamina approach. Biopsy of pathological tissue after operation showed that degenerated and necrotic tissue, accompanied by hemorrhage, lymphoma cells infiltrated into the vascular cavity, and some of them gathered around the vascular wall and in blood clots. Immunohistochemical results showed that B cell antigens CD20 (+ ), CD79a (+ ), paired box protein (PAX)-5 (+ ), and vascular endothelial CD34 (+ ). Epstein-Barr virus-encoded small RNA (EBER) in situ hybridization was positive with about 90%. ③ According to clinical features and related examination result, the final diagnosis was CNS-IVL. Due to severe multisystem damage in medical history, the patient did not receive specialized treatment, such as chemotherapy. Due to the deterioration of CNS-IVL condition, the patient died on January 14, 2022. ④ According to the literature retrieval strategy set in this study, a total of 10 articles were included, involving 11 patients with CNS-IVL involving spinal cord included this case in this study. CNS-IVL patients involving the spinal cord in this group are easily misdiagnosed as myelitis or spinal cord infarction in the early stage. Among them, 3 cases were confirmed by lesion biopsy, 4 cases were confirmed by skin biopsy, and 4 cases were confirmed by autopsy. Improving the early diagnosis rate and followed by either a regimen with cyclophosphamide, vincristine, doxorubicin, and prednisone (CHOP) or R-CHOP (rituximab+ CHOP) will be beneficial for improving the prognosis of patients. Conclusions:CNS-IVL with meningitis onset and progressive involvement of the spinal cord is relatively rare. Patients with Epstein-Barr virus (EBV) positive cerebrospinal fluid should be test for CNS-IVL.
Objective:To investigate the effects of down-regulation of aurora kinase (AURK) B on the proliferation and apoptosis of CALR-mutated MARIMO cells, as well as changes in related genes and signalling. Methods:MARIMO cells derived from a 68-year-old female patient with CALR mutation-positive myeloproliferative neoplasms(MPN) were selected for the study. Lentivirus-mediated short hairpin RNA (shRNA) was used to transfect MARIMO cells, and the cells were categorized into sh-AURKA group, sh-AURKB group and control shRNA (sh-CTRL) group according to the difference of shRNA. The MARIMO cell lines in each group were observed by inverted fluorescence microscope, and their green fluorescent protein (GFP) positivity was detected by flow cytometry (FCM). The reproduction and apoptosis of MARIMO cells in sh-AURKB group and sh-CTRL group were analyzed by FCM, 5-ethynyl-2′-deoxyuridine (EdU)/4′, 6-diamidino-2-phenylindole dihydrochloride (DAPI) staining, and Annexin V/PE reagent. The enrichment of differentially expressed genes (DEG) in sh-AURKB group and sh-CTRL group was analyzed by RNA sequencing (RNA-Seq), and gene ontology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were carried out to screen for significant DEG. The relative expression of mRNA and proteins of DEG were validated by real-time fluorescence quantitative-PCR (RT-qPCR) and Western blotting. Relative expression levels were verified. The comparison of measurement data between two groups was performed by t test. The overall comparison among 3 groups were conducted by one-way analysis of variance, pairwise comparisons between groups were conducted by least-significant difference (LSD) test. This study was in line with World Medical Association Declaration of Helsinki revised in 2013. Results:① The number of MARIMO cells 72 h after transfection was reduced in sh-AURKB group compared with sh-CTRL group [ (0.62±0.03) ×10 5vs (12.44±0.08) ×10 5], and the difference was statistically significant ( t=257.20, P<0.000 1).Compared with sh-CTRL group, the proportion of MARIMO cells in the S-stage in sh-AURKB group was decreased [(33.37 ± 0.75)% vs (42.77 ± 0.91)%], and the proportion of MARIMO cells in G2-M stage was increased [(27.83 ± 0.69)% vs (17.90 ± 0.40)%], the proportion of apoptosis was increased [(16.47 ± 0.70)% vs (2.75 ± 0.13)%], all the differences were statistically significant ( t=13.83, P=0.000 2; t= 23.78, P<0.000 1); t=33.28, P<0.000 1). ② RNA-Seq assay showed that compared to sh-CTRL group, there were 2 787 genes up-regulated and 2 420 genes down-regulated in MARIMO cells in sh-AURKB group. ③ The DEG of sh-AURKB group and sh-CTRL group were mainly annotated in GO nodes such as intracellular region, intracellular membrane border organelle, membrane border organelle, intracellular organelle part, organelle part, etc.. KEGG enrichment analysis showed that a total of 89 signal pathways were significantly enriched. Further screening of DEG-related pathways showed that the 2 groups of significant DEG were NDUFV1, NPRL2, MAP2K4, and CPEB1. ④ RT-qPCR results showed that the relative mRNA expression levels of NPRL2, MAP2K4 and CPEB1 in sh-AURKB group were lower than those in sh-CTRL group, and the differences were statistically significant (LSD- t=14.13, 9.13, 3.10; P<0.000 1, <0.000 1, =0.021). Western blotting results showed that compared with SH-CTRL group, the protein strip grayscale value of NDUFV1/GAPDH in sh-AURKB group increased, while NPRL2/GAPDH, CPEB1/GAPDH, MAP2K4/GAPDH and p-MAP2K4/GAPDH reduced, and the differences were statistically significant (LSD- t=22.60、12.09、7.48、20.48、8.22, P<0.000 1、<0.000 1、=0.000 3、<0.000 1、=0.000 2) Conclusions:AURKB is involved in the proliferation, differentiation and apoptosis of CALR mutant MARIMO cells, and down-regulation of AURKB could induce significant changes in gene expression levels. DEG are mainly enriched in the cell metabolism, cell cycle and apoptosis related pathways.
Mucosal-associated invariant T (MAIT) cells are an evolutionarily conserved T cells subset in vivo, characterized by a highly conserved T cell receptor (TCR) and high sensitivity to microbial metabolites. MAIT cells play different roles in various infectious diseases, autoimmune diseases and malignancies tumors, especially play an important role in protecting the body against pathogenic microbial infections. Current research suggest that MAIT cells may be involved in the development and progression of hematological diseases. This article intends to elaborate on basic characteristics and functions of MAIT cells, as well as research status of MAIT cells in hematological diseases, in order to deepen understanding of MAIT cells.
Objective:To investigate influencing factors of perioperative blood transfusion in patients underwent total knee arthroplasty (TKA).Methods:From January 2015 to November 2022, a total of 211 patients with knee osteoarthritis or knee rheumatoid arthritis who underwent TKA treatment in the First Hospital Affiliated to Army Medical University were selected as research subjects. The median age of these patients was 65 years (61, 72 years), with 45 male and 166 female patients. There were 101 patients who received perioperative blood transfusion and 110 patients who did not. Patients′ clinical data, such as gender, age, preoperative hemoglobin (pHb), preoperative activated partial thromboplastin time (pAPTT), and preoperative prothrombin time (pPT), etc., were collected and analyzed for their impact on perioperative blood transfusion in patients. For univariate factor analysis of clinical data affecting perioperative blood transfusion in patients underwent TKA, Wilcoxon rank sum test, chi-square test or correction for continuity chi-square test was used according to the type of data; and multivariate analysis used unconditional logistic regression analysis. The procedures followed in this study were in accordance with the standards established by the Medical Ethics Committee of the First Affiliated Hospital of the Army Military Medical University [Approval No. (B) KY202252], and all the subjects signed the informed consents for clinical trials.Results:① Results of univariate analysis showed that gender, pHb value, postoperative drainage volume, and whether combined with hypertension may be influencing factors of perioperative blood transfusion in patients underwent TKA ( χ2=6.44, P=0.011; χ2=44.54, P<0.001; χ2=23.74, P<0.001; χ2=4.22, P=0.040). Among the 101 patients who received perioperative blood transfusion, the majority were females (86.1%, 87/101), pHb level< 120 g/L (65.3%, 66/101), postoperative drainage volume> 200 mL (56.4%, 57/101), and without hypertension (78.2%, 79/101). ② Results of multivariate unconditional logistic regression analysis showed that pHb value < 120 g/L ( RR=11.366, 95% CI: 5.433-23.779, P<0.001), pPT≤11 s ( RR=2.330, 95% CI: 1.167-4.652, P=0.016), and postoperative drainage volume> 200 mL ( RR=6.066, 95% CI: 2.951-12.470, P<0.001) were independent risk factors for TKA perioperative blood transfusion. Conclusions:Correction of preoperative anemia, restriction of postoperative drainage, and prevention of patients′ blood in hypercoagulability by supplementing blood volume, may be effective ways to reduce the risk of perioperative blood transfusion for the TKA-treated patients with knee osteoarthritis or knee rheumatoid arthritis.
Objective:To explore the risk factors of chemotherapy related adverse events (AE) in patients with hematological malignancies(HM).Methods:From March 2016 to March 2017, a total of 60 HM patients with chemotherapy related AE were selected as study group( n=60) in Affiliated Hospital of Inner Mongolia Medical University. Meanwhile, a total of 60 HM patients without chemotherapy related AE were successfully matched at a 1∶1 ratio, and included in control group ( n=60) through a combination methods of propensity score matching and traditional matching. There were no statistically significant differences in gender, age, and disease type between two groups.Comparison of clinical data between two groups was performed by the chi-square test. Multivariate analysis of chemotherapy related AE in HM patients was performed by multivariate unconditional logistic regression analysis. This study was in line with World Medical Association Declaration of Helsinki revised in 2013. Results:①The incidence rates of history of liver function damage [26.7% (16/60) vs 10.0% (6/60)] and chronic lung disease [26.7% (16/60) vs 11.7% (7/60)], active infection [31.7% (19/60) vs 15.0% (9/60)], abnormal coagulation function [15.0% (9/60) vs 1.7% (1/60)] and high chemotherapy intensity [73.3% (44/60) vs 40.7% (28/60)] in study group were higher than those of control group, and the differences were significant( χ2=5.57, P=0.018; χ2=4.36, P=0.038; χ2=4.66, P=0.031; χ2=6.98, P=0.008; χ2=8.89, P=0.002). Multivariate analysis results showed that history of liver dysfunction ( OR=3.629, 95% CI: 1.037-3.769, P=0.001) and chronic lung disease ( OR=3.404, 95% CI: 1.057-4.623, P=0.020), active infection ( OR=3.702, 95% CI: 1.026-3.953, P=0.03), abnormal coagulation function ( OR=3.912, 95% CI: 1.034-4.166, P=0.007), and high intensity chemotherapy ( OR=3.397, 95% CI: 1.023-4.375, P=0.02) were independent risk factors for chemotherapy related AE in HM patients. Conclusions:There are many factors that affect the occurrence of chemotherapy related AE in HM patients, especially for patients have history of liver function damage and chronic lung disease, active infection, coagulation dysfunction, etc.. Comprehensive analysis and evaluation should be conducted to develop appropriate treatment plans to effectively reduce incidence of chemotherapy related AE in HM.
CD47, which is widely expressed in various types of cells, is an integrin-associated protein (IAP). Studies in mice have shown that CD47 on platelets and other cells exerts an inhibitory effect on target cell phagocytosis by binding to inhibitory receptor signaling regulatory protein (SIRP) α on macrophages. Autoimmune sensitized cells expressing CD47 are less likely to be phagocytosed by macrophages than are CD47-deficient cells. Results of studies in animal modeled for primary immune thrombocytopenia (ITP) or autoimmune hemolytic anemia showed increased CD47-mediated permeabilization in macrophages. SIRPα acts as a receptor for CD47 and can transmit inhibitory signals into macrophages upon binding CD47. Thus, CD47/SIRPα interaction plays an important role in limiting cell phagocytosis. This article intends to elaborate on current status of research on distribution and its mechanism of CD47 in ITP, aiming to provide ideas and references for the development of new therapeutic measures for ITP.
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only cure method for many hematological malignant diseases in current, but there are also many factors affecting the success of transplantation, such as graft-versus-host disease (GVHD), disease recurrence and severe infection. Graft implantation status is particularly important for early prediction and preemptive intervention of GVHD and recurrence. As a common method to detect the implantation status of grafts after allo-HSCT, chimeric analysis can conduct timely and effectively monitoring of disease status, and provide guidance for subsequent treatment strategies. This article intends to elaborate on current research status of chimerism analysis methods and their roles, cell lineage-specific chimerism analysis, and the application of chimerism analysis in non-malignant diseases (NMD), in order to improve success of allo-HSCT.
Electronic crossmatching (ECM) may be the future development trend of blood transfusion. This technology has been widely used abroad in some developed countries or regions for many years, but it has not yet been widely used in China except Hong Kong. This article intends to elaborate on current application status of ECM at home and abroad, the advantages and disadvantages of ECM compared with traditional serological crossmatching, as well as problems and solutions faced in domestic development of this technology, aiming to provide reference for development of ECM technology in China.
Pure red cell aplasia (PRCA) is a rare anemia disease caused by erythroid hematopoietic failure. According to the etiology, the disease can be divided into congenital PRCA and acquired PRCA. The latter has a long course of disease and is prone to relapse. The first-line treatment, such as cyclosporine A, cyclophosphamide and glucocorticoid are effective for some patients with acquired PRCA, but there are some relapsed/refractory patients with poor prognosis and no respond to previous first-line treatment. In recent years, there are some new immunosuppressive drugs and targeted therapy, which bring hope to relapsed/refractory patients. In order to provide reference for treatment of acquired PRCA patients, this article elaborate on research status in treatment of acquired PRCA in aspects of general support, new immunosuppressive agents, monoclonal antibody, hematopoietic stem cell transplantation (HSCT), and treatment of specific types of secondary acquired PRCA.
Iron is an essential trace element for the human body, and its abnormal metabolism is closely related to occurrence and development of diseases. Leukemia is a heterogeneous hematologic malignancy characterized by uncontrolled clonal proliferation of hematopoietic stem cells. Since leukemia cells have " iron addiction" properties, leukemia treatment strategies using iron chelating agents to chelate iron have been proposed. However, recent studies have found that the regulatory role of iron has two sides. Iron overload induces tumor cell death through various mechanisms, such as ferroptosis, which can play an important anti-tumor role in hematologic neoplasms. This article intends to elaborate on the latest research progress in effects, mechanisms, treatment and prognosis of iron chelation and iron overload-induced ferroptosis in leukemia, and discuss changes in the application of leukemia treatment from iron chelation to ferroptosis.
Objective:To investigate clinical features, diagnosis, therapy, and prognosis of myelodysplastic/myeloproliferative neoplasms-unclassifiable (MDS/MPN-U) patients with thrombocytopenia, and review relevant literature.Methods:On May 11, 2022, a case of patient admitted to Department of Oncology and Hematology, Chongqing the Fourth People′s Hospital was selected as the research subject. This patient was a 67-year-old male. Clinical data such as medical history, clinical features, laboratory and auxiliary examination results were retrospectively analyzed. The patient was diagnosed and treated according to his clinical manifestations, laboratory and auxiliary examination results. Follow-up of the patient was conducted until August 16, 2022. In addition, literature related to the occurrence of MDS/MPN-U with thrombocytopenia in China National Knowledge Infrastructure database, Wanfang Data Knowledge Service Platform, and PubMed database was searched by key words" myelodysplastic/myeloproliferative neoplasm, unclassifiable" " MDS/MPN-U " " thrombocytopenia" in Chinese and English. Literature related to the diagnosis and treatment of MDS/MPN-U with thrombocytopenia was summarized. Time for literature retrieval was set from established to June 30, 2022. Procedure followed in this study was in line with requirements of the World Medical Association Declaration of Helsinki revised in 2013, and informed consent of clinical research was signed with the patient. Results:① This patient was admitted to our hospital for " abnormal blood cells for 3 months" , and routine blood tests in other hospital repeatedly indicated increased white blood cell count and decreased platelet count, and decreased hemoglobin during the course of the disease. ② Results of blood routine examination after admission showed that white blood cell count (WBC), neutrophil count, eosinophils count, basophils count, monocytes count, red blood cell count, hemoglobin (Hb) value and platelet count were 12.01×10 9/L, 10.84×10 9/L, 0.1×10 9/L, 0.02×10 9/L, 0.31×10 9/L, 4.13×10 12/L, 111 g/L and 9×10 9/L, respectively. Bone marrow cell morphology showed that bone marrow hyperplasia was obviously active, and proportion of blast cells occupied nuclear cells was 1%, granuloid cells was 79%, and erythroid cells was 19.5%; bone marrow smear showed 16 megakaryocytes; there were no obvious developmental abnormalities in the three lines of cells. Bone marrow biopsy showed that the degree of proliferation of nucleated cells in the bone marrow was extremely active (about 85% of the hematopoietic tissue area), immature cells were slightly visible, the ratio of granulocytes to erythrocytes was slightly increased, and megakaryocytes were pathologic hematopoietic, and myelodysplastic/myeloproliferative neoplasms (MDS/MPN) was considered. Bone marrow cell flow cytometric immunophenotyping showed that the the proportion of myeloid blast cells occupied nucleated cells was 0.52%, and cell phenotype was not abnormal. Screening for 25 common fusion genes in myeloid leukemia showed negative results. Bone marrow fluorescence in situ hybridization (FISH) results showed that JAK2, FGFR1, PDGFRA, PDGFRB rearrangement were negative. Chromosome karyotype analysis of bone marrow cells showed normal karyotype. Results of gene mutation of myeloproliferative neoplasms (MPN)-related showed that class Ⅰ mutation ASXL1 p. Gly646trpfster12 (mutation frequency was 41.3%), PHF6 p. Tyr301Ter(mutation frequency was 97.5%). Class Ⅱ mutation CUX1 p. Gln326Ter(mutation frequency was 19.1%). ③ This patient was finally diagnosed with MDS/MPN-U with thrombocytopenia and was given thalidomide orally 100 mg/d for long-term use. Regular blood routine tests were performed outside the hospital. Evaluation of curative effect was a clinical benefit when the platelet count was increased to 41×10 9/L(platelet count was below 20×10 9/L before therapy). By the end of follow-up, the patient was generally in good condition with no active bleeding manifestations. ④ Three literature meeting the requirements of this study included a total of 4 patients of MDS/MPN-U with thrombocytopenia including the patient in this study. All 4 patients were male, and 2 patients had enlarged spleens. All patients had normal karyotypes, and BCR/ ABL fusion gene and JAK2V617F gene mutation were negative. The patients received demethylation, immunomodulators, cytotoxic drug, chemotherapy, and other treatments, but efficacy was poor. One patient received allogeneic hematopoietic stem cell transplantation (allo-HSCT), and the disease was stable after 18 months of follow-up. This patient was effective after treatment of thalidomide. Conclusions:MDS/MPN-U with thrombocytopenia is rare. There are some poor prognostic factors, such as advanced age, increased blasts, and genetic mutations with poor prognosis. At present, there is no unified treatment guideline and expert consensus, and the available treatment options are limited. Immunomodulators and allo-HSCT may be effective.
Aplastic anemia (AA) is characterized by bone marrow failure causing pancytopenia and nucleated cell reduction in bone marrow with symptoms of anemia, infections and bleeding. Pathogenesis of AA is complex. Notch signaling pathway has recently been reported to be very important in pathogenesis of AA. For example, Notch signaling pathway regulates the balance of helper T cell (Th)17/regulatory T cell (Treg) through bone marrow mesenchymal stem cells (MSC), the bone marrow microenvironment in AA, such as adipogenesis and osteogenesis, and Th1 polarisation in AA patients by T-box transcription factor (T-bet). Besides, Notch signaling pathway enhances terminal effector (TE) CD8 + T cells function and interferon-γ expression. It activates a major portion of dendritic cells (DC) and macrophage subtypes. In addition, Notch signaling pathway also skews the self-renewal and differentiation of hematopoietic stem cells (HSC). This article reviews research progress on effects of Notch signaling pathway on bone marrow microenvironment, HSC, and immune cells in AA, aiming at exploring its role in pathogenesis of AA, and providing theoretical references in Notch signaling pathway targeted therapy of AA.
Leukemia is a group of clonal hematopoietic malignancies with great heterogeneity, and its pathogenesis has not been fully clarified. Patient-derived tumor xenograft (PDX) animal model can well preserve the heterogeneity, genetic features and tumor microenvironment of tumor, providing a tool for studying the molecular pathogenesis of leukemia and developing new treatments. Therefore, this article summarizes research progress on development and construction of leukemia PDX animal model and application progress of PDX animal model in all kinds of leukemia. In order to provide theoretical and methodological basis for researchers to build leukemia PDX animal model, so that leukemia PDX animal model can provide better guidance for personalized medication leukemia patients, and lay foundation for the realization of leukemia precision medicine.
Glucose phosphate isomerase (GPI) deficiency is a rare autosomal recessive disease which mainly caused by abnormal structure and lack of activity of GPI due to GPI gene variation. The clinical manifestations of the disease include neonatal hyperbilirubinemia, congenital nonspherocytic hemolytic anemia, acute hemolytic crisis caused by infection or other inducements, while some cases are accompanied by neurological symptoms. GPI activity determination and genetic testing are common methods for diagnosis of GPI deficiency. This article focuses on the research status of pathogenesis, clinical features, laboratory tests, treatment and prognosis of GPI deficiency, in order to provide reference for clinical diagnosis and treatment of this disease.
Objective:To investigate diagnosis and treatment strategy of paroxysmal cold hemoglobinuria (PCH) complicated by venous thromboembolism (VTE) patients.Methods:On December 30, 2019, a case of an 85 years-old male patient with PCH complicated by VTE who was admitted to Fifth Affiliated (Zhuhai) Hospital of Zunyi Medical University was selected as research subject. Clinical data such as medical history, clinical features, laboratory and auxiliary examination results were retrospectively analyzed. The patient was diagnosed and treated according to his clinical manifestations, laboratory and auxiliary examination results. The patient was followed up until December 28, 2021. China National Knowledge Infrastructure database, Wanfang Data Knowledge Service Platform and PubMed database were searched using " autoimmune hemolytic anemia", " paroxysmal cold hemoglobinuria", " paroxysmal cold hemoglobinuria", " venous thromboembolism", " thrombotic microangiopathy", " thrombotic events", " AIHA", " VTE" and " TE" as Chinese and English keywords, and diagnosis and treatment data of patients with PCH complicated by VTE were summarized. The time for literature retrieval was from inception of the databases to May 30, 2022. This study was approved by the Ethics Committee of the Fifth Affiliated (Zhuhai) Hospital of Zunyi Medical University (Approval No. 2021ZH0089) and clinical research informed consent form was signed by the patient.Results:① This patient was admitted to our hospital because of " poor anorexia, dizziness, intermittent fever for 15 d, and disturbance of consciousness for 1 d". During seeking treatment in other hospital, the patient′s hemoglobin (Hb) value decreased progressively, and the primary and secondary sides are not compatible in crossmatching test before blood transfusion. Because of unable to complete blood matching and blood transfusion treatment, the patient was transferred to our hospital for further treatment. ② On admission, blood routine examination of the patient showed that hemoglobin value was 37 g/L, leukocyte and platelet count increased, erythrocyte sedimentation rate (ESR) increased, immunoglobulin (Ig)G and lactate dehydrogenase (LDH) level increased, and direct antiglobulin test was positive, cold agglutination test was negative, and result of cold-hot hemolytic test was positive. Morphology of bone marrow cells showed that bone marrow proliferation was obviously active, mainly granulocytic and erythroid hyperplasia, and no abnormal primitive and immature cells were found. Result of bone marrow cells immunophenotyping via flow cytometry showed that primitive cells accounted for 0.5% of nuclear cells, distributed scattered. Monocytes accounted for 6.5% of nuclear cells and were phenotypic mature. Granulocytes accounted for 67.0% of nuclear cells, and no obvious abnormal development was found. Results of color Doppler ultrasound and venography showed thrombosis in deep vein and small saphenous vein of right lower limb. ③ This patient was diagnosed as PCH and hyper-IgG sydrome. Methylprednisolone 2 mg/(kg·d) was given and plasma exchange was performed at the same time. Washed red blood cell was transfused. On the 9th day after admission, the patients developed lower limb VTE. Rivaroxaban (15 mg/time, 2 time/d) anticoagulation was given immediately and inferior vena cava filter was implanted. On the 24th day of hospitalization, patient′s condition was improved and discharged. After discharge, the patient was treated with cyclosporine 5 mg/(kg·d) for 8 months, while rivaroxaban (15 mg/time, 2 time/d) was given for one week, and then rivaroxaban (20 mg/d) was used for 6 months until removing the inferior vena cava filter. By the end of follow-up, there was no recurrence of acute intravascular hemolysis and venous thromboembolism, and the patient was in good condition. ④ According to literature search strategy set in this study, a total of 6 articles in English were included, involving 65 patients with AIHA complicated by thrombotic events (TE), including 52 cases of warm AIHA (wAIHA), 2 cases of condensing set syndrome (CAS), 2 cases of mixed AIHA, and 8 cases without clear points. No case of PCH complicated by TE was reported in the literature. Most TE cases occurred during active hemolysis, and did not receive prophylactic anticoagulation therapy. TE included VTE, visceral vascular embolism, intracranial venous (sinus) thrombosis, superficial thrombophlebitis and other organ thromboembolism. In this case of PCH complicated by VTE, VTE occurred during acute hemolysis, and did not receive prophylactic anticoagulation therapy.Conclusions:This case of patient with acute hemolysis in PCH did not receive anticoagulant therapy in time, which led to thromboembolism of lower extremities. In course of clinical diagnosis and treatment, during the period of acute hemolysis of AIHA, it is necessary to prevent TE as early as possible in patients without anticoagulant contraindications.
Multiple myeloma (MM) is a malignant disease with abnormal plasma cell proliferation. At present, with the applications of proteasome inhibitor (PI), immunomodulator, CD38 monoclonal antibody and chimeric antigen receptor-T cell(CAR-T) and other therapeutic methods, the prognosis of patients with MM has improved significantly, but MM is still an incurable disease. Therefore, further exploration of pathogenesis of MM and development of new drugs to improve prognosis of MM patient are particularly crucial. Due to the fact that metabolic changes are fundamental feature of cancer, MM cells also undergo this metabolic recombination process. This article aims to elaborate research status on the main metabolic abnormalities of MM, such as glycolysis, metabolic syndrome, and glutamine (Glu) metabolism, as well as the impact of metabolic changes on MM drug resistance, in order to provide a theoretical basis for elucidating the role of metabolism in the development and progression of MM, potential metabolic targets for future treatment, optimizing treatment plans of MM patients, and improving their prognosis.
Objective:To investigate clinical characteristics and prognosis of patients with central nervous system lymphoma (CNSL).Methods:From January 2010 to December 2021, a total of 56 patients with CNSL who were admitted to the Department of Hematology, Second Affiliated Hospital of Harbin Medical University were selected as the study subjects. According to the type of CNSL, patients were divided into primary CNSL (PCNSL) group ( n=30) and secondary CNSL (SCNSL) group ( n=26). Using a retrospective study method, clinical data were collected from all patients, including pathological type, international prognostic index (IPI) score before treatment, β2-microglobulin (MG) value, lactate dehydrogenase (LDH) level, Ki-67 expression level, and overall response rate (ORR). The comparison of overall survival (OS) curves between two groups was conducted by log-rank test. Univariate and multivariate analyses using Cox proportional hazards regression model were performed to identify clinical characteristics affecting the prognosis of patients. There were no statistically significant differences in the baseline data such as composition ratios of gender, age, and pathological type between two groups ( P>0.05). This study was in line with World Medical Association Declaration of Helsinki revised in 2013 and informed consents were obtained from the subjects. Results:① There was a statistically significant difference in the composition ratios of IPI scores between PCNSL group and SCNSL group in this study ( χ2=13.303, P<0.001). There was no statistically significant difference in the composition ratios of pathological types between patients in two groups ( χ2=7.168, P=0.127). And the pathological type of patients in both groups was mainly diffused large B cell lymphoma (DLBCL), accounting for 96.7% (29/30) and 73.1% (19/26), respectively. ② The ORR of 52 evaluable CNSL patients in this study was 61.5% (32/52). The ORR of patients in PCNSL group was 75.0% (21/28), which was higher than that of 45.8% (11/24) in SCNSL group, and the difference was statistically significant ( χ2=0.465, P=0.031). ③ The OS time of all 56 CNSL patients was (24.0±4.5) months. The 2-year OS rate of patients in PCNSL group was 56.6%, which was higher than that of 25.7% in SCNSL group, and the difference was statistically significant ( χ2=8.970, P=0.003). ④ The results of univariate and multivariate analysis of Cox proportional hazards regression model revealed that radiotherapy combined with chemotherapy was an independent protective factor for OS of CNSL patients ( HR=0.258, 95% CI: 0.097-0.687, P=0.007). Conclusions:DLBCL was the main pathological type in patients with CNSL, and combined use of chemotherapy combined with radiotherapy is an independent protective factor for prognosis of patients. Patients with PCNSL exhibit better prognosis compared to those with SCNSL.
Diffuse large B-cell lymphoma recent years (DLBCL) is the most common type of aggressive non-Hodgkin lymphoma (NHL) in adults, and its incidence has increased in recent years. DLBCL patients′ abnormality of molecular biology and change of histomorphology have high heterogeneity, so their prognostic factors are diverse. Prognostic evaluation standard of DLBCL patients, such as International Prognostic Index (IPI) and cell of origin (COO) were widely used, and the evaluation method that have potential predictive value, such as dynamic changes of circulating free DNA (cfDNA), vitamin D or albumin in peripheral blood, and systemic inflammation have become a research hotspot in China and abroad. IPI is a prognosis evaluation based on the clinical characteristics of patients in the era of simple chemotherapy, which is simple and easy to operate. However, in the era of immunotherapy and targeted therapy, the accuracy of IPI in evaluating patients′ prognosis is constantly impacted. COO can identify the disease type of patients more accurately, but higher sample requirements and expensive testing costs limit its application, while the level of cfDNA, vitamin D, albumin, and related inflammatory indicators can be obtained from peripheral blood samples for detection, and are easy to operate and economical, can make up for the shortcomings of IPI and COO. This article reviews research progress of DLBCL related prognostic factors to provide a theoretical basis for guiding the selection of the best prognostic evaluation method in clinical work.
Objective:To study the effect of microRNA (miRNA)-29b on the proliferation and invasion of multiple myeloma (MM) cells by regulating the signal transducer and activator of transcription (STAT) 3 signaling pathway and its mechanism.Methods:The human MM cell line U266 and normal plasma cells were selected as the research objects. U266 in the logarithmic growth phase was inoculated into 6-well plates, and set up mimic group ( n=6, adding miRNA-29b mimic), inhibitor group ( n=6, adding miRNA-29b inhibitor), negative control (NC) group ( n=6, adding miRNA-29b NC object) and blank group ( n=6, no treatment). The relative expression levels of miRNA-29b in U266 and normal plasma cells were detected by real-time fluorescent quantitative (RT)-PCR. Transwell test kit was used to detect cell invasion ability, 3-(4, 5)-dimethylthiahiazol-2-y1)-2, 5-diphenyltetrazolium bromide (MTT) test kit was used to detect cell proliferation activity, and Western blotting was used to detect the relative expression levels of STAT3 and its phosphorylated STAT3 (p-STAT3) protein in cells. The comparison of relative expression levels of miRNA-29b between two groups was performed by independent sample t test. The overall comparison of relative expression level of miRNA-29b, cell proliferation activity, number of invasive cells, relative expression levels of STAT3 and p-STAT3 protein among multiple groups were conducted by one-way analysis of variance; pairwise comparisons between groups were conducted by LSD- t test. Results:① The relative expression level of miRNA-29b in U266 in the blank group was (1.00±0.10), which was lower than that of normal plasma cells (4.25±0.41), and the difference was statistically significant ( t=18.987, P<0.001). ②The relative expression level of miRNA-29b in the mimic group was significantly higher than that of NC group[(3.87±0.21) 0.93±0.09)], the difference was statistically significant (LSD- t=39.921, 7.975; P<0.001, 0.001), there was no significant difference between NC group and blank group[(0.93±0.09) vs (1.00±0.10); LSD- t=1.084, P=0.291].③For cell proliferation activity, after 24 hours of culture, there was no significant difference in the value of optical density among mimic group, NC group and inhibitor group ( F=3.722, P=0.089). After cultured for 48 and 72 h, the value of optical density in mimic group were (0.53±0.05) and (0.91±0.07), respectively, which were significantly lower than those of NC group[(0.72±0.06) and (1.23±0.10)](LSD- t=3.561, 3.982; P=0.012, 0.007). Meanwhile the value of optical density of inhibitor group was (0.90±0.08) and (1.66±0.12), respectively, which were significantly higher than those of NC group (LSD- t=3.370, 5.039; P=0.015, 0.002). ④ Compared with NC group, the number of U266 invasive cells in mimic group was significantly decrease[(23.6±2.1) vs (154.4±7.2); LSD- t=18.428, P<0.001], the inhibitor group was significantly increased[(85.2±5.2) vs (154.4±7.2); LSD- t=20.702, P<0.001].⑤ The relative expression levels of STAT3 and p-STAT3 protein in U266 in mimic group were significantly lower than those of NC group[(0.53±0.06) and (0.38±0.05) vs (1.26±0.10) and (0.98±0.09)], the inhibitor group[(2.92±0.21) and (2.37±0.19)]was significantly higher than those of NC group, and the differences were statistically significant(LSD- t=9.082, 8.116, 20.647, 19.081; P<0.001, 0.001, 0.001, 0.001). Conclusions:The expression of miRNA-29b was downregulated in MM cells. Overexpression of miRNA-29b may inhibit the proliferation and invasion of MM cells by regulating the activity of STAT3 signaling pathway.
