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Objective @#To investigate the value of methyltransferase-like protein 16 (METTL16) in the clinical di- agnosis and prognostic prediction of multiple myeloma (MM) patients . @*Methods @#The expression level and prog- nostic potential of each gene involved in N6 -methyladenosine ( m6A) modification in MM were respectively ana- lyzed in the databases of the Multiple Myeloma Research Foundation (MMRF) and the Genotype-Tissue Expression Proj ect (GTEx ) . Bone marrow specimens from 26 patients with initial diagnosis of MM and 19 patients with MM af- ter treatment with standard regimens and peripheral blood specimens from 24 normal subjects were collected respec- tively , and the expression levels of m6A genes were determined by qRT-PCR. The correlation between METTL16 expression and various laboratory and clinical indexes was analyzed: hemoglobin ( Hb) , white blood cell count ( WBC) , platelet count (PLT) , blood creatinine (Scr ) , serum calcium (Ca2 + ) , β-microglobulin ( β-MG) , bone destruction , ISS stage , type , and overall survival (OS) in the patients with primary diagnosis . The expression lev- els of interleukin (IL) -4 , IL-6 , IL-10 , IL-18 and chemokine ligand 2 ( CCL2) , CCL3 , CCL4 in the specimens were further examined and their correlation with the expression of METTL16 was investigated . @*Results @#Database analysis suggested that METTL16 expression was significantly higher in MM patient samples compared with normal controls , which was associated with poor prognosis and had certain diagnostic value . qRT-PCR results showed that the expression level of METTL16 in the bone marrow of patients with initial diagnosis of MM was significantly higher than that of treated patients and normal controls . Its expression was positively correlated with hemoglobin , leuko- cytes and stage , and its expression was positively correlated with CCL4 expression .@*Conclusion @#METTL16 expres- sion was significantly elevated in patients with MM , and its expression level was correlated with anemia , more bone destruction and worse stage , which might indicate a poor prognosis . The significant correlation between the expres- sion of METTL16 and CCL4 suggests that METTL16 may play a corresponding pathogenic role through the relevant pathway. METTL16 will have significant clinical value in the management of MM .
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Objective:To explore the prognostic value of lymphocyte subsets in adult hemophagocytic syndrome (HPS).Methods:A total of 172 adult HPS patients diagnosed in 8 medical centers from January 2013 to August 2020 were selected for the study, of whom 87 were male (50.6%, 87/172), and 85 were female (49.4%, 85/172), with 68 survivors and 104 deaths. The clinical data were summarized, and variables such as lymphocyte subsets, immunoglobulin characteristics and fibrinogen were retrospectively analyzed, and the correlation between the mentioned variables and patient prognosis was analyzed. The optimal cut-off values of continuous variables were calculated by MaxStat, and the prognostic factors of HPS patients were screened based on the Cox proportional hazard regression model.Results:The median age of HPS patients was 56 (42, 66) years old, and the 5-year cumulative survival rate was 37.4% (37.4/100). The median age, platelet and albumin were 48 (27, 63) years, 84×10 9/L and 32.3 g/L in the survival group, and 59 years, 45.5×10 9/L, and 27.3 g/L in the death group, respectively. The differences between the two groups was statistically significant ( Z=?3.368, P=0.001; Z=?3.156, P=0.002; Z=?3.431, P=0.001). Patients with differentiated cluster 8+(CD8+)<11.1%, CD3+<64.9%, CD4+>51%, and CD4/CD8 ratio>2.18 had poor prognosis (χ 2=7.498, P=0.023; χ 2=4.169, P=0.041; χ 2=4.316, P=0.038; χ 2=9.372, P=0.002). Multivariable analysis showed that CD4/CD8 ratio, age, fibrinogen and hemoglobin were independent prognostic factors in HPS patients ( HR=2.435, P=0.027; HR=5.790, P<0.001; HR=0.432, P=0.018; HR=0.427, P=0.018). Conclusion:Peripheral blood lymphocyte subsets can be used to evaluate the prognosis of patients with HPS; CD4/CD8 ratio, age, fibrinogen, and hemoglobin are independent prognostic factors in HPS patients.
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Objective:To investigate the correlation between nutritional status and nosocomial infection in elderly patients with acute leukemia.Methods:A total of 202 elderly patients with acute leukemia hospitalized in the Department of Hematology of the First Affiliated Hospital of Anhui Medical University from June 2015 to December 2017 were randomly included as research objects.The nutritional status of patients was assessed by the Patient-Generated Subjective Global Assessment(PG-SGA), and the blood routine and biochemical indexes were compared among patients with different nutritional conditions.The correlations between clinical characteristics and PG-SGA score and between nutritional status and nosocomial infection were analyzed.Univariate analysis and multivariate Logistic regression analysis were used to evaluate the related factors for the nosocomial infection.Results:The hemoglobin and albumin were higher in patients with PG-SGA score of 0-8[(97.02±2.86)g/L and (39.78±0.50)g/L, respectively]than in patients with PG-SGA score ≥ 9[(83.02±3.28)g/L and (37.71±0.71)g/L]( P=0.003, 0.016). And C-reactive protein(CRP)was lower in patients with PG-SGA score of 0-8[(33.98±5.34)mg/L]than in patients with PG-SGA score ≥ 9[(58.82±8.36)mg/L]( P=0.015). There were significant differences in PG-SGA scores among patients with different age, disease stage, disease type and gastrointestinal reaction( t=-6.562, 3.292, 2.869 and 2.268, P=0.000, 0.001, 0.006 and 0.041). The PG-SGA score was positively correlated with the incidence of nosocomial infection( r=0.544, P=0.000). Logistic regression analysis showed that PG-SGA score was an independent risk factor( OR=2.11, 95% CI: 1.66-2.71, P=0.000). And albumin was a protective factor( OR=0.86, 95% CI: 0.77-0.93, P=0.000)for the nosocomial infection in elderly patients with acute leukemia. Conclusions:The nutritional status is closely related to the occurrence of nosocomial infection in elderly patients with acute leukemia.Elderly acute leukemia patients with malnutrition should be given adequate nutritional support as soon as possible to improve their nutritional status and improve prognosis.
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AIM: To evaluate the clinical efficacy and safety of oral proteasome inhibitor ixazomib in the treatment of multiple myeloma. METHODS: Eighty patients with multiple myeloma treated with ixazomib-containing therapy in the department of hematology, the First Affiliated Hospital of Anhui Medical University from January 2019 to December 2020 were retrospectively analyzed, including 38 patients with relapsed/refractory multiple myeloma (RRMM)and 42 patients who switched treatment due to adverse events (AEs) after initial induction therapy with bortezomib. Treatment was a two-drug or three-drug regimen containing ixazomib, and the clinical efficacy and safety of ixazomib were evaluated. RESULTS: The overall response rate (ORR) of relapsed/refractory patients was 50%, ≥ VGPR 21.05%; the ORR of patients who switched treatment was 83.33%, compared with the ORR before switching (78.57%), the response rate was further improved, of which 45.24%(19/42) patients had deepened response; the main hematological AEs included granulocyte and platelet count reduction and anemia, non-hematological AEs were mainly diarrhea and fatigue. CONCLUSION: Ixazomib shows good clinical efficacy and safety in patients with RRMM and bortezomib-intolerant MM.
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Objective To investigate the effect of leukemia-related genes on drug resistance in patients with acute myeloid leukemia (AML). Methods 74 patients with newly diagnosed AML were selected and 54 leukemia-associated genes of all patients were sequenced by second-generation gene sequencing. The gene with the highest mutation rate was further analyzed in association with resistance to several common chemotherapy medicines in in vitro drug sensitivity assays. In addition, in vitro drug resistance data were compared with the clinical data of patients. Results The TET2 gene was the most frequent mutation among 74 patients with newly diagnosed AML, with 11 positive patients. Among these 11 TET2 positive patients, 9 (81. 82％ ) were resistant to daunorubicin, while only 4 (6. 35％ ) out of 63 TET2 negative patients were resistant to daunorubicin. Besides, there was no significant difference between in vitro resistance rate to daunorubicin and the clinical data of patients. Conclusion TET2 gene mutation is associated with resistance to daunorubicin in AML patients, which may become an important indicator of the therapeutic efficacy of DA regimen.
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Objective To investigate the changes in the proportion of regulatory T (Treg) cells and in the levels of cytokines secreted by these cells in the peripheral blood in the patients with chronic myeloid leukemia (CML). Methods The enrolled subjects consisted of 30 CML patients who were newly diagnosed , 20 CML patients who were under the effective treatment of tyrosine kinase inhibitors (BCR-ABL 210 transcript ratio is below 10%) and 20 healthy donors whose age and sex were matched .Flow cytometry was used to detect CD4+CD25 high CD127 low /-Treg cells and CD4+ T cells.The enzyme linked immunosorbent assay was used to determine the plasma concentra -tions of interleukin-10(IL-10), transforming growth factor-β1(TGF-β1) and IL-35.Results The proportions of Treg cells in CD4+ T cells were similar among the three groups .As concerns the three kinds of Treg-associated cy-tokines, there were no significant differences in the plasma concentrations of IL -10 among the three groups.Howev-er, compared with the treatment group and the control group , the plasma concentrations of TGF -β1 and IL-35 in the newly diagnosed patients significantly increased (P <0.001), with no significant difference between the treat -ment group and the control group.Conclusion Though the proportion of Treg cells did not significantly change in the newly diagnosed patients, the plasma concentrations of TGF-β1 and IL-35 indeed significantly enhanced , sug-gesting the dysfunction of Treg cells in the newly diagnosed patients might be associated with the progression of dis -ease.Effective treatment of tyrosine kinase inhibitors could down -regulate the plasma levels of these cytokines to baseline, suggesting that monitoring these cytokines might evaluate the efficacy of therapy .
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We aimed to investigate the expression of inter-leukin 12 [IL-12] family cytokines [IL-12, IL-23, IL-27 and IL-35] and their relevant cytokines [IFN-gamma, IL-4, IL-17A and IL-10] in patients with chronic immune thrombocytopenia [cITP] as well as the effect of high-dose dexamethasone [HD-DXM] treatment on this expression. DXM was administered orally at a dose of 40 mg per day for 4 consecutive days to 38 patients with cITP. We measured the plasma levels of IL-12p70, IL-23, IL-27, IFN-gamma, IL-4 and IL-17A before and after treatment and also in 36 matched healthy controls, by means of FlowCytomix[Tm]technology. The plasma levels of IL-10 and IL-35 were measured by enzyme-linked immunosorbent assay. Significantly higher plasma levels of IL-12p70, IL-23, IL-27, IFN-gamma and IL-17A were observed in cITP patients than in controls [p < 0.01], and after HD-DXM treatment, these levels decreased significantly [p < 0.01]. However, significantly lower plasma levels of IL-4, IL-10 and IL-35 were observed in cITP patients than in controls [p < 0.01]; after the HD-DXM treatment, these levels had increased significantly in the cITP patients [p < 0.01]. Moreover, the cytokine levels of patients who attained a complete response returned to the levels of normal controls [p > 0.05] but were not corrected in the patients who had no response [p <0.01]. The patients with cITP had abnormal expression of the IL-12 family cytokines and their relevant cytokines levels, and HD-DXM treatment corrected the derangement of plasma cytokines. Measuring cytokine levels may help in the clinical assessment of cITP
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Humains , Adulte , Adulte d'âge moyen , Sujet âgé , Femelle , Mâle , Cytokines , Purpura thrombopénique idiopathique , DexaméthasoneRÉSUMÉ
<p><b>OBJECTIVE</b>To investigate the different outcomes by dexamethasone in adults immune thrombocytopenia purpura (ITP) with different types of platelet specific-autoantibodies.</p><p><b>METHODS</b>A total of 185 ITP were enrolled, 61 males and 124 females, with a median age of 42 (18-83) years, including 117 newly diagnosed, 35 persistent, and 33 chronic cases. All the patients received the dexamethasone at an initial dose of 40 mg per day for 4 days and a low dose of 5-10 mg for 3-4 weeks. The platelet specific-autoantibodies were identified by the modified monoclonal antibody-specific immobilization of platelet antigen (MAIPA) assay.</p><p><b>RESULTS</b>Among the IgG positive patients, the response rates in anti-GPIIb/IIIa antibody, anti-GPIbα antibody, both antibody positive, and both antibody negative were 87.5%, 50.0%, 68.0%, and 72.3% (χ²=11.489, P<0.05), respectively. Among the IgM positive patients, the response rates in the four groups were 82.1%, 71.4%, 61.9%, and 68.9% (χ²=2.719, P=0.437), respectively. Among the GPIbα antibody positive patients, the response rates in IgG alone, IgM alone, both positive, and both negative were 52.4%, 59.1%, 76.1%, and 77.9% (χ²=10.811, P<0.05), respectively. Among the GPIIb/IIIa antibody positive patients, the response rates in the four groups were 73.3%, 71.0%, 78.6%, and 66.3% (χ²=1.374, P=0.719), respectively.</p><p><b>CONCLUSION</b>ITP patients with GPIbα-IgG antibody have worse response to dexamethasone treatment.</p>
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Adolescent , Adulte , Sujet âgé , Sujet âgé de 80 ans ou plus , Femelle , Humains , Mâle , Adulte d'âge moyen , Jeune adulte , Anticorps monoclonaux , Autoanticorps , Plaquettes , Dexaméthasone , Complexe glycoprotéique IIb-IIIa de la membrane plaquettaire , Purpura thrombopénique idiopathiqueRÉSUMÉ
Objective To explore the alterations, relationship and clinical significance of CD4 +CD25 +CD127 low/ - regulatory T cells ( Treg ) and lymphocyte subsets in peripheral blood of patients with acute myelocytic leukemia ( AML) . Methods The level of peripheral blood lymphocyte subsets and Treg of untreated AML patients and com-plete remission( CR) patients were tested by flow cytometry,and were compared with that of 30 normal controls. Re-sults The proportions of Treg were much higher in untreated AML patients and CR patients than in normal con-trols, while the mean proportion of Treg in untreated AML patients was higher than that in CR patients(P<0. 05). The proportions of NK( CD3 -CD16 +CD56 +) cells in untreated AML patients and CR patients were both decreased compared with normal controls,and the mean proportion of NK cells in untreated AML patients was lower than that in CR patients(P<0. 05). Compared with the normal controls,the proportions of CD3 +T cell, CD4 +T cell,and the ratio of CD4 +/CD8 + decreased in untreated AML patients ( P <0. 05 ) , but the proportions of CD8 +T cell was higher than in normal controls;the proportions of CD3 +T cell, CD4 + T cell, CD8 +T cell and the ratio of CD4 +/CD8 + in CR patients were close to the proportions in normal controls, but there was significant difference between CR patients and untreated AML patients(P<0. 05). Conclusion The increase of Treg, CD8 +T cell and decrease of NK cells, CD3 +T cell, CD4 +T cell, and the ratio of CD4 +/CD8 + in peripheral blood of patients with AML in-dicate that the immune function of patients with AML is depressed. Treg control the immune response of CD8 +T cells,at the same time inhibit the natural immune response of NK cells, playing a major role in the disorders of CD4 +T cells and CD8 +T cell balance,and closely relate with the development of AML. The immune treatment of patients with AML will be optimised by reducing the amount of Treg or removing the suppression function.
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Objective To analyze the clinical characteristics and prognostic factors in patients with primary gastrointestinal diffuse large B-cell lymphoma (PGI-DLBCL),and to improve the diagnosis and treatment of PGI-DLBCL.Methods Retrospective analysis was conducted in 51 cases of PGI-DLBCL between January 2009 and August 2013.The data included clinical manifestations,pathological features,treatment regimens and prognosis.Results 51 patients included 31 males and 20 females,the range of ages was from 16 to 80 years old,median age was 48 years old.The major clinical presentation were abdominal pain,abdominal distension,abdominal mass,nausea and vomiting,abdominal mass.The occurrences in stomach,small intestine,colon,rectum and multiple involvement were 56.86 ％,29.41％,7.84 ％,1.90 ％ and 3.92 ％ respectively.The mass bigger than 10 cm was found in 13 cases (25.49 ％).47.06 ％ (24/51) of the cases belonged to the GCB subtype and 52.94 ％ (27/51) belonged to the non-GCB subtype.There was no significant impact of lymphoma cell origin,disease distribution (stomach or intestinal) and mass on prognosis of lymphoma treatment.The univariate analysis revealed that the patients with Lugano stage Ⅳ,increased level of serum lactate dehydrogenase (LDH),modified-international prognosis index (modified IPI) 3-5 and increased level of CA125 had poor prognosis (all P ＜ 0.05).There was no difference of survival rate between patients treated with rituximab plus chemotherapy and single CHOP like therapy.Surgery plus postoperative chemotherapy significantly improved survival of patients treated with simple chemotherapy (P ＞ 0.05).Conclusion The clinical Lugano stage,IPI score,increased LDH and CA125 are important prognostic factors of PGI-DLBCL.
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Objecfive To detect the specific autoantibodies against platelet in idiopathic thrombocytopenic purpura (ITP) and to study the relationship between these autoantibodies and the severity of ITP as well as therapeutic effect.Methods Autoantibodies (GPⅡbⅢa and GPIb) against platelet glycoprotein was measured by a monoclonal antibody immobilization of platelet antigen assay (MAIPA) in 40 ITP patients.Results 10 patients had mono-specific antibodies to GP Ⅱ bⅢa and 6 patients had mono-specific antibodies to GPIbα.Another 20 patients had antibodies to both antigens and 4 patients had no detectable antibody to either platelet antigen.There Was negative correlation between the antibody against GPⅡbⅢa(b=-0.071,P<0.01),CPIbα(b=0.092,P<0.01) and platelet counts.The ratio of refractory cases in patients with antibodies to both antigens(8/20) was significantly higher than that in patients with mono-specific antibodies(1/16)(χ2=6.09,P<0.05).Conclusion The specific autoantibadies against platelet might be valuable for discrininafion of idiopathic thrombocytopenic purpura and non immune thrombocytopenia.The types of antibodies are related with severity of ITP and therapeutic effect.
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Objective To explore mechanism of human bone mesenchymal stem cell(MSC)in treating patients with aplastic anemia(AA)in vitro.Methods MSCs were separated with Percoll(1.073 g/mL)and cultured in low glucose DMEM.T cells were harvested by using nylon column.MSCs of various concentrations were added to PHA induction T cell proliferation cultures with AA patients.The proliferation of T cell was measured by MTT method. The CD25(IL-2R)expression rates of CD~+_3 T cells was analyzed by flow cytometry .Results MSCs were planted in 96-well plates(2?10~4/well for group A,1?10~4/well for group B)and cocultured with T cell isolated from peripheral blood of AA patients. Peripheral blood T cell noncocultured with MSC acted as the control group.MSCs significantly inhibit PHA-induced T cell proliferation and the CD25 expression of CD~+_3 T cells in patients with AA(P