Objective: To analyze and compare therapy responses, outcomes, and incidence of severe hematologic adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia (CML) . Methods: Data of patients with chronic phase CML diagnosed between January 2006 and November 2022 from 76 centers, aged ≥18 years, and received initial flumatinib or imatinib therapy within 6 months after diagnosis in China were retrospectively interrogated. Propensity score matching (PSM) analysis was performed to reduce the bias of the initial TKI selection, and the therapy responses and outcomes of patients receiving initial flumatinib or imatinib therapy were compared. Results: A total of 4 833 adult patients with CML receiving initial imatinib (n=4 380) or flumatinib (n=453) therapy were included in the study. In the imatinib cohort, the median follow-up time was 54 [interquartile range (IQR), 31-85] months, and the 7-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.2%, 88.4%, 78.3%, and 63.0%, respectively. The 7-year FFS, PFS, and OS rates were 71.8%, 93.0%, and 96.9%, respectively. With the median follow-up of 18 (IQR, 13-25) months in the flumatinib cohort, the 2-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.4%, 86.5%, 58.4%, and 46.6%, respectively. The 2-year FFS, PFS, and OS rates were 80.1%, 95.0%, and 99.5%, respectively. The PSM analysis indicated that patients receiving initial flumatinib therapy had significantly higher cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) and higher probabilities of FFS than those receiving the initial imatinib therapy (all P<0.001), whereas the PFS (P=0.230) and OS (P=0.268) were comparable between the two cohorts. The incidence of severe hematologic adverse events (grade≥Ⅲ) was comparable in the two cohorts. Conclusion: Patients receiving initial flumatinib therapy had higher cumulative incidences of therapy responses and higher probability of FFS than those receiving initial imatinib therapy, whereas the incidence of severe hematologic adverse events was comparable between the two cohorts.
Adult ; Humans ; Adolescent ; Imatinib Mesylate/adverse effects* ; Incidence ; Antineoplastic Agents/adverse effects* ; Retrospective Studies ; Pyrimidines/adverse effects* ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy* ; Treatment Outcome ; Benzamides/adverse effects* ; Leukemia, Myeloid, Chronic-Phase/drug therapy* ; Aminopyridines/therapeutic use* ; Protein Kinase Inhibitors/therapeutic use*

OBJECTIVE: To analyze and evaluate the efficacy of Rh phenotype matched blood transfusion. METHODS: The increasing of hemoglobin (Hb) and hemolysis tests in the patients treated by Rh matched red blood cells or not, as well as the first time unmatched transfusions and the unmatched transfusions happened again after a period (≥10 d) were retrospectively analyzed. RESULTS: A total of 674 times transfusions in 120 patients were evaluated. The increasing of Hb in each unit was higher in the patients treated by Rh matched blood transfusion (vs unmatched) [(33.397±1.475) g/U vs (29.951±1.304) g/U, P=0.033], while the increasing of Hb at first time unmatched transfusion and the second time unmatched transfusion was not statistically different[ (28.942±2.083) g/U vs (30.686±1.737) g/U, P=0.589]. The level of lactate dehydrogenase were related to erythrocyte washing, irradiation, period of validity and the second time unmatched transtusion (all P<0.05); the levels of total bilirubin (TBil), direct bilirubin (DBil) and indirect bilirubin (IBil) between the first time unmatched transfusion and the second time unmatched transfusion were statistically different (all P<0.05). CONCLUSION For the patients need multiple blood transfusions, Rh phenotype matched blood transfusion can reduce the exposure to Rh allogenic antigens, improve the efficacy and ensure the safety of blood transfusion.
Bilirubin ; Blood Transfusion ; Erythrocyte Transfusion/adverse effects* ; Hemoglobins/analysis* ; Humans ; Phenotype ; Retrospective Studies

OBJECTIVE: To identify one case of rare Hb Lepore-BW associated with IVS-II-654 heterozygous mutation in Sichuan area. METHODS: The blood routine examination and hemoglobin electrophoresis methods were used to analyze the blood routine parameters, HbA₂ and HbF in the samples of peripheral blood in proband and his parents, as well as the cord blood of pregnant woman. The detection of thalassemia gene and Sanger sequencing methods were used to detect the hemoglobin mutations. RESULTS: The result showed that the Hb Lepore-BW heterozygous mutation was detected in the father of the proband, while a rare Hb Lepore-BW with IVS-II-654 heterozygous mutation was detected in the proband, as well as his mother and cord blood were both detected as IVS-II-654 heterozygous mutation. CONCLUSION The study identified a rare Hb Lepore-BW with IVS-II-654 heterozygous mutation, which was characterized by intermediate β-thalassemia. It is necessary to hemoglobin electrophoresis combined with routine blood testing in prenatal screening.
Female ; Hemoglobins, Abnormal/genetics* ; Heterozygote ; Humans ; Infant, Newborn ; Male ; Mutation ; Pregnancy ; Prenatal Diagnosis ; beta-Thalassemia/genetics*

With the progress of medical technology, cloning hematopoietic was found to be widely exist in normal people. Because of its clinical significance and prognosis is unclear, it is named clonal hematopoiesis of indeterminate potential(CHIP), which has been detected in blood diseases such as myelodysplastic syndrome and lymphoma, and proven to be related to poor prognosis. Recently, CHIP has been also detected in patients with multiple myeloma (MM). In this article, the definition and influencing factors of CHIP, clinical significance, prognosis and treatment in MM were reviewed.
Clonal Hematopoiesis ; Hematopoiesis ; Humans ; Multiple Myeloma ; Mutation ; Myelodysplastic Syndromes

Objective:To investigate the regulatory effects of mitofusin 1 (MFN1) on lipopolysaccharide (LPS)-induced Raw264.7 mouse macrophages pyroptosis and to provide reference for further study on the prevention of inflammation and fibrosis caused by macrophage dysfunction.Methods:Raw264.7 mouse macrophages were cultured in vitro and used to construct a model of LPS-induced pyroptosis. CCK-8 staining, PI staining, LDH release assay and Western blot were used to verify the Raw264.7 pyroptosis induced by LPS. MFN1 expression was detected by Western blot. DCFH-DA probe was used to detect the synthesis of total reactive oxygen species (ROS); Mito-SOX was used to detect mitochondrial ROS; JC-1 mitochondrial membrane potential was detected by fluorescence probe to reflect mitochondrial damage. Based on Ubibrowser database, it was predicted that MFN1 could bind to a variety of E3 ubiquitin ligases. Then, immunofluorescence and co-immunoprecipitation (CO-IP) were used to analyze MFN1 ubiquitination. An overexpression plasmid for MFN1 was constructed and transfected into Raw264.7 cells to detect the changes in pyroptosis and mitochondrial function. Results:LPS could induce the pyroptosis of Raw264.7 cells and mitochondrial dysfunction. MFN1 expression was decreased after LPS stimulation. Ubiquitinated MFN1 was detected by CO-IP. Ubiquitination inhibitor MG-132 inhibited LPS-induced expression of pyroptosis-related proteins including NLRP3, Pro-caspase-1, Caspase-1, IL-1β and IL-18 and improved mitochondrial function. MFN1 overexpression relieved the mitochondrial dysfunction and pyroptosis of Raw264.7 cells induced by LPS.Conclusions:The ubiquitination of MFN1 induced by LPS was involved in mitochondrial dysfunction and macrophage pyroptosis, suggesting that MFN1 was a potential target for the treatment of macrophage-induced inflammation and related diseases.

OBJECTIVE: To study the effects of FLT3-ITD length on 32D cell proliferation, apoptosis and sensitivity to FLT3 inhibitor, so as to provide references for stepwise therapy of FLT3-ITD mutated acute myeloid leukemia patients. METHODS: Three different FLT3-ITD mutants with same or adjacent insert sites were selected and constructed in an eukaryotic expression vector. FLT3-ITD mutants stably expressed 32D cell strains were selected with the help of lentivirus system and IL3 free cell culture medium. The proliferation and apoptosis of 32D cell strains after AC220 treatment were detected. RESULTS: FLT3-ITD mutants (ITD1, ITD2 and ITD3) stably expressed 32D cell strains were constructed successfully. In the absence of IL3 factor, the proliferation number of ITD1, ITD2 and ITD3 cell strains were mounted up to 2.3 folds, 3.7 folds, and 4.3 folds after 48 hours, respectively. Under the exposure of FLT3 inhibitor AC220, the IC CONCLUSION FLT3-ITD mutant expressed cell strains with longer ITD show higher capacity of proliferation and higher tolerance to AC220 treatment.
Apoptosis ; Cell Proliferation ; Humans ; Leukemia, Myeloid, Acute/genetics* ; Mutation ; Protein Kinase Inhibitors ; Tandem Repeat Sequences ; fms-Like Tyrosine Kinase 3/genetics*

OBJECTIVE: To study the effect of PX-12 on apoptosis of multiple myeloma (MM) cell line induced by bortezomib. METHODS: MM cell line H929 cells were divided into PX-12 group, bortezomib group, combination group, and control group. 5.0 μmol/L PX-12, 20 nmol/L bortezomib, combination of the two drugs, and DMSO were given to the above mentioned group, respectively. After culture for 24, 48, and 72 hours, the changes of cell viability were observed, the MM cell activity was detected by MTT method, and the cell cycle distribution and apoptosis of each group was detected by flow cytometry. The intracellular ROS level was measured by H RESULTS: MTT assay showed that after culture for 72 hours, the activity of H929 cells in PX-12 group (P<0.05) and bortezomib group (P<0.01) was significantly lower than that in the control group, while that in the combination group was decreased most significantly (P<0.01). After culture for 48 hours, cells in G1 phase in PX-12 group was decreased to 40%, while cells in S phase and G CONCLUSION PX-12 can increase the apoptosis of MM cell line H929 induced by bortezomib, which may be caused by increasing of ROS level.
Apoptosis ; Bortezomib/pharmacology* ; Cell Line, Tumor ; Cell Proliferation ; Humans ; Multiple Myeloma

OBJECTIVE: To investigate the clinical significance of AML patients with 11q23/MLL rearrangement, and to evaluate the effect of those mutations on the AML patients. METHODS: 53 cases involving translocations of chromosome 11q23 were identified by chromosome banding analysis. MLL rearrangements were detected by fluorescence in situ hybridization and/or multiplex nested PCR. The samples were screened for mutations in the candidate genes FLT3-ITD, FLT3-TKD, TET2, N-RAS, ASXLI, EZH2, DNMT3, C-Kit, NPM1, WT1, CEBPA by using genomic DNA-PCR and deep-sequencing. RESULTS: 21/53 MLL-rearranged AML cases showed at least one additional chromosomal aberrations. The most common additional aberration was +8. Gene mutations were observed in 23 cases (43.4%) and most cases showed singal mutation. N-RAS mutation was more frequent (8 cases, 15.1%), followed by WT1 mutation in 4 cases (7.5%), FLT3-ITD mutation in 3 cases, ASXL1 mutation in 2 cases, DNMT3A mutation in 2 cases, EZH2 mutation in 1 case, c-Kit17 mutation in 1 case, FLT3-TKD mutation in 1 case, and FLT3-ITD and TKD mutation coexistent in 1 case. No mutation was detected in CEBPA, NPM1, C-KIT8, TET2. Median OS for gene mutated patients was 8.5 months and 13 months for no mutated patients. Median OS for patients who received hematopoietic stem cell transplantation (HSCT) was 22.5 months and 7.5 months for patients who olny received chemotherapy. CONCLUSION A relatively high mutation frequency is observed in AML patients with 11q23/MLL rearrangements and most cases shows single mutation. The RAS signaling pathway alterations are most common. Gene mutation does not affect the OS of these patients, who show poor prognosis. A significantly higher Hb at initial diagnosis in FLT3 mutated patients is significantly higher than that in FLT3 wild-type cases. Patients who underwent HSCT show a better prognosis than those only received chemotherapy.
Chromosomes, Human, Pair 11 ; Hematopoietic Stem Cell Transplantation ; Humans ; In Situ Hybridization, Fluorescence ; Leukemia, Myeloid, Acute ; Mutation ; Prognosis ; fms-Like Tyrosine Kinase 3

OBJECTIVE: To summarize and elucidate the characteristics and evolvement of Chinese medicine (CM) patterns reflecting the physical and mental conditions of participants in the Mars 500 long-term closed environment. METHODS: The DS01-T Digital TCM Four-Diagnostic Instrument and CM Inquiring Diagnostic Questionnaire were used to collect information from 6 participants in the Mars 500 International Joint Research Project, through diagnostic methods of observation, palpation and inquiry according to CM theory. During the 520 days of the experiment, data collection was performed 37 times; a total of over 400 digital images of tongues and facial complexion and over 20,000 data were collected. These data were then analyzed by a team of experts in CM, statistics, and data mining. RESULTS: The CM pattern evolvement of participants in the long-term closed environment followed some common trends. Qi deficiency was the main CM pattern observed, with individual features depending on constitutional differences [manifested in varying degrees of accompanying patterns of Gan (Liver) qi stagnation, Pi (Spleen) deficiency, dampness encumbering, or yin deficiency]. CONCLUSION The research has verified the effectiveness of CM syndrome differentiation based on the four diagnostic methods, which should serve as a solid foundation for observation, monitoring, and intervention in regard to the health conditions of astronauts in long-term space flights in the future.

OBJECTIVE: To investigate the clinical features, accompanying gene mutation characteristics and prognostic factors of adult patients with acute myeloid leukemia with mutated NPM1 (NPM1AML). METHODS: Seventy-three patients with newly diagnosed adult NPM1AML were selected. The mutations of 22 genes were detected by second generation sequencing and 43 fusion genes of AML were detected by real-time fluorescent quantitative PCR. The Kaplan-Meier survival curve and Cox multivariate regression analysis were used to study the prognostic factors. RESULTS: A total of 74 NPM1 site mutations were detected in 73 patients with NPM1AML. The incidence rates were 92.0% L287fs, 2.7% Q289fs and W288fs, 1.4% L258fs and Q289H, among which 1 patient had 2 NPM1 mutations; the different mutation sites had no effect on the prognosis of NPM1AML. The median value of NPM1 variant allele frequency (VAF) was 35.4% (1.8%-56.6%). Based on the uppermost quartile of 38.4%, the patients were classified as NPM1 VAF>38.4% (NPM1AML) and NPM1 VAF≤38.4% (NPM1AML). Compared with NPM1AML, the early mortality rate was statistically significantly higher (33.3% vs 7.3%, P<0.05), and median EFS (148 d，95%CI 58-238 d vs 372 d，95%CI 264-480 d) (P<0.01) and median OS (179 d 95%CI 6-352 d vs 444 d) (P<0.01) were significantly shorter in NPM1 AML. A total of 126 accompanying gene mutation sites were detected in 87.7% of patients with NPM1AML. The patients with NRAS gene mutation displayed a higher rate of complete remission (100% vs 58%) (P<0.05) and longer median OS (not reached to 320 d, 95%CI 150-490 d) (P<0.05). The 43 fusion genes were examined in 65 out of 73 cases of NPM1AML, and in all the patients the fusion gene test was negative. Multivariate analysis showed that NPM1 VAF>38.4% was an independent prognostic factor for EFS (HR=3.1, 95% CI 1.6-6.4, P<0.01) and OS (HR=3.0, 95% CI 1.4-6.2, P<0.01). CONCLUSION The NPM1 gene mutation in AML patients often is accompanied by other gene mutations, while the coexistence of fusion genes is rare; high NPM1 mutant allele burden is an independent prognostic factor for adult AML patients with mutated NPM1.
Alleles ; Humans ; Leukemia, Myeloid, Acute ; genetics ; Mutation ; Nuclear Proteins ; genetics ; Prognosis ; fms-Like Tyrosine Kinase 3