1.The clinical application value of METTL16 in patients with multiple myeloma
Wanjie WANG ; Han XU ; Tingting XU ; Jing BAO ; Ruixiang XIA
Acta Universitatis Medicinalis Anhui 2024;59(4):690-697
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 Project(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 a-nalysis 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.
2.Value of lymphocyte subsets in assessing the prognosis of adult hemophagocytic syndrome
Ziyuan SHEN ; Chenlu HE ; Ying WANG ; Qian SUN ; Qinhua LIU ; Ruixiang XIA ; Hao ZHANG ; Yuqing MIAO ; Hao XU ; Weiying GU ; Chunling WANG ; Yuye SHI ; Jingjing YE ; Chunyan JI ; Taigang ZHU ; Dongmei YAN ; Wei SANG ; Kailin XU ; Shuiping HUANG ; Xiangmin WANG
Chinese Journal of Laboratory Medicine 2022;45(9):914-920
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.
3.The correlation study between nutritional status and nosocomial infection in elderly patients with acute leukemia
Xiaowen CHEN ; Lili HOU ; Ruixiang XIA
Chinese Journal of Geriatrics 2021;40(7):895-898
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.
4.Meta-analysis of Non-immune Related Adverse Event s Caused by ICIs Alone or Combined with Routine Che- motherapy in the Treatment of Non-small Cell Lung Cancer
Qingshu ZHANG ; Ruixiang CHEN ; Jin WEN ; Conglong XIA ; Jiao HE ; Qian ZHAO
China Pharmacy 2021;32(12):1506-1514
OBJECTIVE:To systematically evaluate the occurren ce of non-immune related adverse events (AEs)caused by immune checkpoint inhibitors (ICIs)alone or combined with routine chemotherapy in the treatment of non-small cell lung cancer (NSCLC),and to provide evidence-based reference for clinical medication. METHODS :Retrieved from PubMed ,Cochrane Library,Embase,CNKI,CBM,VIP and Wanfang database during the inception to Oct. 2020,randomized controlled trials (RCT) about ICIs alone or combined with routine chemotherapy (trial group )versus routine chemotherapy or placebo combined with routine chemotherapy (control group ) were collected. After literature screening and data extraction ,the quality of included literatures were evaluated with bias risk evaluation tool recommended by Cochrane systematic evaluator manual 5.1.0. Meta-analysis was performed by using Rev Man 5.3 software and Stata 15.0 software. Sensitivity analysis was conducted with Stata 15.0 software. Inverted funnel plot and Egger ’s test were used to analyze publication bias. RESULTS :A total of 20 RCTs were included , involving 12 283 patients. Results of Meta-analysis showed that the incidence of all grades and s evere AEs ,anemia,neutropenia, vomiting and alopecia as well as the incidence of thrombocytopenia,nausea and peripheral neuropathy in all grades of trial group were all significantly lower than control com group(P<0.05). There was no statistical significance in the incidence of termination of treatment , death, severe thrombocytopenia, severe nausea and severe peripheral neuropathy or all grades and severe diarrhea between 2 groups(P>0.05). Subgroup analysis showed that the incidence of all grade and total severe AEs ,the incidence of anemia ,neutropenia,thrombocytopenia,clinically relevant symptoms (except for severe diarrhea),termination of treatment and death of patients receiving ICIs alone in trial group were significantly lower than control group(P<0.05). The incidence of ermination of treatment and death ,the incidence of nausea ,vomiting,diarrhea and alopecia in all grade ,severe diarrhea of patients receiving ICIs and chemotherapy in trial group were all significantly higher than control group (P<0.05). Sensitivity analysis supported the above results. Analyze publication bias results showed that the possibility of publication bias in this study was small. CONCLUSIONS :For NSCLC patients ,the safety of ICIs is better than that of routine chemotherapy or placebo combined with routine chemotherapy in the treatment-related AEs ,hematologic toxicity and clinically relevant symptoms ;however,the risks of treatment discontinuation ,AEs-induced deaths ,and all-grade nausea ,vomiting, diarrhea,alopecia and severe diarrhea will be increased in the ICIs combined with routine chemotherapy.
5. Clinical efficacy and safety of ixazomib in the treatment of multiple myeloma
Jing BAO ; Xiaowen CHEN ; Liang XIA ; Yuchen ZHAO ; Ruixiang XIA ; Hailong XIA
Chinese Journal of Clinical Pharmacology and Therapeutics 2021;26(7):782-786
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.
6.Clinical analysis of micafungin in prevention of fungal infection in neutropenic stage in patients with allogeneic hematopoietic stem cell transplantation
Qingsheng LI ; Jing NI ; Ming RUAN ; Jian HONG ; Ruixiang XIA ; Qingshu ZENG ; Mingzhen YANG
Journal of Clinical Medicine in Practice 2019;23(8):78-80,84
Objective To explore the efficiency and safety of micafungin in preventing fungal infection in neutropenic stage in patients with allogeneic hematopoietic stem cell transplantation (allo-HSCT). Methods The clinical data of 116 patients with allo-HSCT were collected, among whom 23 patients had a history of pulmonary fungal infection before transplantation. All patients were treated with micafungin for 50 mg daily from the beginning of pretreatment to recovery of neutropenia.Results Six patients were clinically diagnosed as pulmonary fungal infections. No serious adverse reactions were observed during the clinical observation, and concentration of cyclosporin A was not adjusted. By the end of follow-up, 83 patients survived. Conclusion Micafungin is safe and effective in preventing fungal infection in neutropenic stage after allo-HSCT without affecting the concentration of cyclosporine A in blood.
7.Clinical analysis of micafungin in prevention of fungal infection in neutropenic stage in patients with allogeneic hematopoietic stem cell transplantation
Qingsheng LI ; Jing NI ; Ming RUAN ; Jian HONG ; Ruixiang XIA ; Qingshu ZENG ; Mingzhen YANG
Journal of Clinical Medicine in Practice 2019;23(8):78-80,84
Objective To explore the efficiency and safety of micafungin in preventing fungal infection in neutropenic stage in patients with allogeneic hematopoietic stem cell transplantation (allo-HSCT). Methods The clinical data of 116 patients with allo-HSCT were collected, among whom 23 patients had a history of pulmonary fungal infection before transplantation. All patients were treated with micafungin for 50 mg daily from the beginning of pretreatment to recovery of neutropenia.Results Six patients were clinically diagnosed as pulmonary fungal infections. No serious adverse reactions were observed during the clinical observation, and concentration of cyclosporin A was not adjusted. By the end of follow-up, 83 patients survived. Conclusion Micafungin is safe and effective in preventing fungal infection in neutropenic stage after allo-HSCT without affecting the concentration of cyclosporine A in blood.
8.Resistance to daunorubicin in acute myeloid leukemia is associated with mutations in the TET2 gene
Liu YANG ; Jian GE ; Ruixiang XIA
Acta Universitatis Medicinalis Anhui 2018;53(2):246-250
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.
9.Changes of regulatory T cells and their associated cytokines in patients with chronic myeloid leukemia
Xixi CHEN ; Mingzhen YANG ; Ruixiang XIA
Acta Universitatis Medicinalis Anhui 2016;51(7):1015-1018
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 .
10.The significance of Treg and T lymphocyte subsets in acute myelocytic leukemia
Lingjun KONG ; Jian GE ; Ruixiang XIA
Acta Universitatis Medicinalis Anhui 2015;(4):512-514,515
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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