OBJECTIVES: To investigate the role of METTL3 and FOXO3 in anthracycline resistance in acute myeloid leukemia (AML) cells. METHODS: Methylated RNA immunoprecipitation sequencing (MeRIP-seq) and transcriptome sequencing (RNA-seq) were performed in anthracycline-resistant and sensitive HL60 and K562 cells with lentivirus-mediated knockdown or overexpression of METTL3 and FOXO3. TCGA and GSE6891 datasets were used for analysis of the clinical and gene expression data of AMI patients. FOXO3 expressions at the mRNA and protein levels in the transfected cells were detected with RT-qPCR and Western blotting, and the changes in cell proliferation and apoptosis were evaluated using CCK8 assay and flow cytometry; the expression of m⁶A-modified mRNA and mRNA stability of FOXO3 was detected analyzed using MeRIP-qPCR and RT-qPCR. Functional enrichment analysis of the differential genes in the transfected cells was performed. RESULTS: Differential gene analysis in anthracycline-resistant versus sensitive AML cells and in cells with METTL3 knockdown revealed the enrichment in FoxO and autophagy pathways (P<0.05), and the anthracycline-resistant cells showed significantly increased m⁶A modification of FOXO3. FOXO3 expression was positively correlated with METTL3 expression. METTL3 knockdown significantly reduced FOXO3 mRNA stability and its protein levels in anthracycline-resistant AML cells, which exhibited higher m6A-modified FOXO3 expression levels than their sensitive counterparts. Database analysis, Kaplan-Meier analysis and RT-qPCR results suggested that a high FOXO3 expression was associated with a poor prognosis of AML patients. In anthracycline-resistant AML cells expressing higher FOXO3 levels than the sensitive cells, lentivirus-mediated overexpression of FOXO3 significantly enhanced cell proliferation and suppressed cell apoptosis. Inhibiting autophagy using an autophagy inhibitor (Baf.A1) obviously enhanced the inhibitory effect of adriamycin on resistant AMI cells and cells overexpressing FOXO3. CONCLUSIONS METTL3 promotes FOXO3 expression via m6A modification, and FOXO3-driven autophagy contributes to anthracycline resistance in AML cells by enhancing cell proliferation and suppressing cell apoptosis.
Humans ; Forkhead Box Protein O3/genetics* ; Leukemia, Myeloid, Acute/genetics* ; Drug Resistance, Neoplasm ; Methyltransferases/genetics* ; Autophagy ; Anthracyclines/pharmacology* ; HL-60 Cells ; Apoptosis ; Cell Proliferation ; K562 Cells

Nephroptosis,a rare condition in urology,often results from inadequate support of the kidney's perinephric fat structures,leading to excessive renal mobility.It typically occurs in lean,tall,young females.Some cases manifest with abdominal pain and renal dysfunction.Open nephropexy,laparoscopic nephropexy and percutaneous nephropexy are all effective methods in the treatment of nephroptosis,among which percutaneous nephropexy is associated with less trauma and lower costs.Modifications to percutaneous nephropexy by the authors'team are also introduced mentioned in this article.

Infection is an important cause of early death in patients with acute leukemia, and exploring how to reduce infectious complications during intensive chemotherapy for acute leukemia is of great theoretical and practical significances. Studies have shown that the intestinal flora of leukemia patients undergoes significant changes in the process of receiving treatment, and the changes in the intestinal flora of acute leukemia patients are closely related to the occurrence of infectious complications after chemotherapy. This article reviews the characteristics of intestinal flora, the relationship between intestinal flora and infectious complications, and the methods to restore the diversity of intestinal flora in acute leukemia patients.

Objective: To evaluate clinical outcomes of autologous and allogeneic peripheral blood stem cell transplantation (PBSCT) for aggressive peripheral T-cell lymphoma (PTCL). Methods: From June 2007 to June 2017, clinical data of PTCL patients who underwent PBSCT were assessed retrospectively. Results: Among 41 patients, 30 was male, 11 female, and median age was 38(13-57) years old. Seventeen patients with autologous PBSCT (auto-PBSCT) and 24 patients with allogeneic PBSCT (allo-PBSCT) were enrolled in this study. Eight patients (8/17, 47.1%) in auto-PBSCT group were ALK positive anaplastic large cell lymphoma (ALCL), 7 patients (7/24, 29.2%) with NK/T cell lymphoma and 9 patients (9/24, 37.5%) with PTCL-unspecified (PTCL-U) in allo-PBSCT group (P=0.035). There were 58.8% patients (10/17) in complete response (CR) status and 11.8% (2/17) in progression disease (PD) status before transplantation in auto-PBSCT group, and 8.3% (2/24) in CR status and 45.8% (11/24) in PD status before transplantation in allo-PBSCT group (P=0.026). The 2-years cumulative overall survival (OS) were (64.0±10.8)% and (53.5±9.7)% for auto-PBSCT and allo-PBSCT respectively (P=0.543). The 2-years cumulative disease-free survival (DFS) were (57.1±12.4)% and (53.5±10.6)% for auto-PBSCT and allo-PBSCT respectively (P=0.701). In patients with dead outcomes after PBSCT, 83.3% (5/6) of death cause was relapse in auto-PBSCT and 41.7% (5/12) of death cause was relapse in allo-PBSCT. Conclusion Both auto-PBSCT and allo-PBSCT were effective for PTCL. Allo-PBSCT maybe was better than auto-PBSCT for high-risk PTCL with poor prognosis.

Online teaching has recently become a new way in medical education, to which great importance has been attached by domestic educational circles. The design principles, overall framework and functional structure of the online course platform in Peking Medical College were thus described with its implementation and characteristics summarized in the hope of providing certain reference for its building in domestic medical colleges and universities.

OBJECTIVETo explore the influence of relapse and survival by chronic graft versus host disease (cGVHD) in patients with acute myeloid leukemia (AML) after allogeneic hematopoietics stem cell transplantation (allo-HSCT).

METHODSFifty-five AML patients received allo-HSCT were retrospectively reviewed. Relapse rate and overall survival (OS) were analyzed according to cGVHD.

RESULTScGVHD significantly decreased the relapse rate of AML patients after transplantation within 2 years when compared with those without cGVHD (8.7% vs 38.6%, P=0.019), however, cGVHD had no effect on the long-term relapse rate (22.8% vs 5.9%, P=0.217). cGVHD had no effect on OS within 2 years (78.3% vs 61.0%, P=0.155) but could decrease the rate of long-term survival (63.7% vs 100%,P=0.01). cGVHD also could reduce the rate of relapse (8.3% vs 46.2%, P=0.044) and enhanced the rate of survival (83.3% vs 47.2%, P=0.045) in patients with high risk AML after allo-HSCT in 2 years, while it had no effect on the relapse rate and OS in patients with low and intermediated risk AML in early and late phase. Moreover, compared with the rate of relapse(38.6%) in patients without cGVHD, the rate of relapse were lower in patients with limited cGVHD and intensive cGVHD (27.3% and 31.3%, respectively) but the long-term survival was significantly lower (53.3%, P=0.001) in those patients with intensive cGVHD after all-HSCT.

CONCLUSIONThe benefit effect of cGVHD mainly took place within 2 years after allo-HSCT in AML patients especially in those with high risk, while in late phase after allo-HSCT, cGVHD especially intensive cGVHD had an effect on reducing long-term survival.

Chronic Disease ; Graft vs Host Disease ; Hematopoietic Stem Cell Transplantation ; Humans ; Leukemia, Myeloid, Acute ; Recurrence ; Retrospective Studies ; Transplantation, Homologous

Quality management covers every corner of hospital services,which upholds full-process quality management,continuous quality improvement and smooth management with patients at the center.By means of building a 3-tier quality management framework at the hospital,development of quality management criteria,appraisal indicators and documentation and use of quality management tools,quality management defects were identified from a third-party perspective.This effort has significantly improved quality of care at the hospital,and elevated the management execution and general service quality of the hospital.

BACKGROUNDAllogeneic peripheral blood stem cell transplantation from unrelated donors (UR-PBSCT) is an alternative treatment for many hematologic diseases due to lack of human leukocyte antigen (HLA)-identical sibling donors. This study aimed to evaluate the impact of the degree of the HLA match on the clinical efficacy of UR-PBSCT.

METHODSPatients who underwent UR-PBSCT from September 2003 to September 2012 were retrospectively investigated. They were divided into three groups according to high-resolution molecular typing. SPSS version 17.0 was used to analysis and compare the statistics of engraftment, incidence of GVHD, other complications and survival among the groups.

RESULTSOne hundred and eleven patients received UR-PBSCT, 60 of them with an HLA matched donor (10/10), 36 of them with a one locus mismatched donor (9/10), and 15 of them with a two loci mismatched donor (8/10). Similar basic characteristics were found in the three groups. No differences were found in engraftment of myeloid cells or platelets in the three groups (P > 0.05). Two-year cumulative incidence of relapse, overall survival (OS) and disease-free survival (DFS) among those three groups were similar (P > 0.05). The cumulative incidence of 100-day III-IV aGVHD in the HLA matched group and the one HLA locus mismatched group were significantly lower than that in the two HLA loci mismatched group (3.3%, 8.6%, and 26.7%, P = 0.009). The occurrence rate of new pulmonary infections in the HLA matched group was lower than in the two HLA mismatched groups (26.67%, 52.78%, and 41.18%, P = 0.035). The cumulative incidence of 100-day and 2-year transplantation related mortality (TRM) in two HLA loci mismatched group was higher than in the HLA matched group and in the one HLA locus mismatched group, (8.4%, 11.8% and 33.3%, P = 0.016) and (12.3%, 18.7% and 47.5%, P = 0.002).

CONCLUSIONSHLA mismatch will not significantly impact the engraftment or 2-year survival after UR-PBSCT, but two mismatched HLA loci may increase the cumulative incidence of severe aGVHD and TRM.

Adolescent ; Adult ; Child ; Female ; HLA Antigens ; immunology ; Humans ; Male ; Middle Aged ; Peripheral Blood Stem Cell Transplantation ; standards ; Unrelated Donors ; Young Adult

Objective To compare the efficacy and adverse effects of bortezomib+adriamycin+dexamethasone (PAD) and vincristine + adriamycin + dexamethasone (VAD) regimens in untreated multiple myeloma (MM). Methods There were 26 and 28 new diagnosed MM patients in PAD and VAD groups. Both clinical effects and adverse effects were observed. Patients accepted VAD or PAD regimens for 2-4 cycles and followed up for 7-27 months. Results There were 10, 5 and 11 patients accepted 2, 3 and 4 cycles in PAD group, and 6, 11 and 11 in VAD group. In PAD group, there were 2, 14, 9, 1 and 0patients achieved complete remission (CR), very good partial remission (VGPR), partial remission (PR),stable disease (SD) and progressive disease (PD); in VAD group, the number were 0, 4, 12, 10 and 2.The rate of patients who achieved good efficacy (CR+VGPR) in PAD group was 61.5%, which was higher than that in VAD group (14.3%).The incidences of infection and gastrointestinal symptoms were similar in the two groups, while the incidences of peripheral neuropathy, thrombosis and Herpes Zoster infection in PAD group were higher than those in VAD group. Conclusions Compared with the conventional VAD chemotherapy, PAD may improve CR and VGPR rates in new diagnosed MM, while it may bring more and severer toxicities in peripheral neuropathy, thrombosis and Herpes Zoster infection. Preventive medical care is necessary in PAD protocol.