The novel HLA-B*40:555 allele identified by Sanger dideoxy nucleotide sequencing in a Chinese individual.

HLA-B*40:555 differs from HLA-B*40:01:02:01 by one nucleotide in exon 3.

Circular RNA PVT1 Regulates Cell Proliferation, Migration, and Apoptosis by Stabilizing c-Myc and Downstream Target CXCR4 Expression in Acute Myeloid Leukemia

Objective: This study aimed to investigate the role and mechanism of circular RNA PVT1 (circPVT1) in patients with acute myeloid leukemia (AML). Materials and Methods: The expression of circPVT1 in 23 patients with de novo AML (not acute promyelocytic leukemia, not APL) and cell lines were detected by RT-qPCR. Loss of function assays were carried out to explore the influence of silenced circPVT1 on the proliferation, migration, and apoptosis in the THP-1 cell line. CCK-8 assays, trans-well assays, and annexin V/PI staining assays were performed to assess proliferation, migration, and apoptosis, respectively. Results: CircPVT1 was highly expressed in AML patients and myeloid cell lines compared to healthy controls. Higher expression of circPVT1 was related to shorter overall survival (OS) and relapse-free survival (RFS) in AML patients. Cell viability and migration were inhibited and apoptosis was increased when circPVT1 was knocked down in THP-1 cells. Knockdown of circPVT1 resulted in marked suppression of c-Myc protein with no significant change in mRNA levels. We also found that circPVT1 knockdown markedly increased the phosphorylation of c-Myc Thr-58, which was responsible for c-Myc degradation. Silencing of c-Myc caused a significant decrease in CXCR4 mRNA and protein expression, whereas the overexpression of c-Myc caused the opposite result, suggesting that CXCR4 is a target molecule of c-Myc. Finally, we found that overexpression of c-Myc could partially reverse circPVT1 knockdown-induced anti-tumor effects on THP-1 cells in vitro. Conclusion: Our findings showed that circPVT1 was highly expressed in AML patients and was related to shorter OS and RFS. CircPVT1 may exert an oncogenic effect in THP-1 cells by stabilizing c-Myc protein expression and downstream target CXCR4 expression. These data indicate that circPVT1 may be a promising therapeutic target for AML.

Acute myeloid leukemia with myelodysplasia-related changes and blasts of the mixed T/myeloid phenotype: a case report.

A rare but clinically important diagnostic dilemma arises when cases meet the criteria for both acute myeloid leukemia with myelodysplasia-related changes (AML-MRC) and mixed phenotype acute leukemia, especially those that evolve from myelodysplastic syndrome. We describe a 56-year-old male patient who presented with cytopenias and was initially diagnosed with myelodysplastic syndrome with single lineage dysplasia. Nearly 1 year later, this patient progressed to acute leukemia, and his blast cells simultaneously expressed T-lymphoid and myeloid antigens. Cytogenetic analysis showed a 20q deletion, and next-generation sequencing showed mutations of ASXL1, NRAS, PHF6, RUNX1, TP53, and PIGA. He was diagnosed with AML-MRC with blasts of the mixed T/myeloid phenotype according to the latest World Health Organization guidelines. In accordance with the treatment principles of AML-MRC, we chose an AML-like regimen for four cycles, but the patient did not achieve remission. Finally, we adhered to the treatment principles of mixed phenotype acute leukemia, and he achieved remission after a course of ALL-like regimen chemotherapy.

[Coadsorption of Heavy Metal and Antibiotic onto Humic Acid from Polder River Sediment].

To clarify the interactions between heavy metals, antibiotics, and humic acid, copper (Cu2+), oxytetracycline (OTC), norfloxacin (NOR), and humic acid samples from river sediment in the Polder area were selected to build single and coexisting systems. Groups of experiments were designed to investigate the kinetics, thermodynamics, and isotherms of Cu2+, OTC, and NOR adsorption onto humic acid in single and Cu2++OTC and Cu2++NOR coexisting systems (concentration ratio=1:1). The physicochemical properties of humic acid were analyzed by scanning electron microscopy (SEM), X-ray diffraction (XRD), BET tests, and IR spectroscopy, and the possible adsorption mechanisms are discussed. The results showed that the humic acid was a typical amorphous material with a negative charge and non-uniform porous structure, and the pore size was at the mesoporous scale. In the single systems, the saturated adsorption capacity (qm) of Cu2+, OTC, and NOR onto humic acid was 33.043, 19.512, and 26.676 mg·g-1, respectively. In the Cu2++OTC system, the qm of Cu2+ and OTC was 38.053 and 25.965 mg·g-1, respectively. In the Cu2++NOR system, the qm of Cu2+ and NOR was 39.187 and 32.728 mg·g-1, respectively. The adsorption behaviors in the single and coexisting systems were similar and the adsorption processes were well fitted by the pseudo-second-order kinetic equation; the Sips model provided good descriptions for the isothermal adsorption equilibrium. Moreover, adsorption thermodynamics were characterized by spontaneous endothermic reactions with the reduction of free energy and the increase of enthalpy and entropy. It can be concluded that Cu2+ combines with OTC and NOR to form complexes, which increases the number of species available for adsorption by humic acid. Also, adsorbed Cu2+ can combine with free OTC and NOR in a bridging manner. Thus, a more favorable adsorption situation occurred in the coexisting systems. The IR characteristics of the carboxyl, phenolic hydroxyl, ketone, and aldehyde groups of humic acid changed by different degrees after adsorption, indicating that oxygen-containing functional groups generally participated in the adsorption reactions.

Adsorption behaviors of the pristine and aged thermoplastic polyurethane microplastics in Cu(II)-OTC coexisting system.

In this work, the hypothesis that thermoplastic polyurethane (TPU) microplastics (MPs) could form complex toxic pollution by absorbing both antibiotics and heavy metals simultaneously was proposed. The unique features of the adsorption of Cu(II) and oxytetracycline (OTC) on the pristine TPU and photo-aged (aged) TPU MPs in single and coexisting system were investigated, which included the kinetics, isothermal equilibrium and thermodynamics. The possibly synergistic or competitive effects between Cu(II) and OTC were also evaluated. The results showed that the adsorption process of Cu(II) and OTC could be described well by pseudo-second-order kinetic equation. The entire process could be divided into two stages: internal diffusion and external diffusion. The Sips model could give good fitting for the isothermal adsorption equilibrium. The thermodynamic parameters depicted the endothermic nature of adsorptions and the process was spontaneous. In the coexisting system, synergistic or competitive effects depended critically on the ratio of concentrations (Cu(II) vs OTC). When the ratio was 1:1, Cu(II) significantly enhanced the adsorption of OTC, while OTC showed a weak effect on Cu(II) adsorption. The synergies could be attributed to the formation of Cu(II)-OTC complex and the bridging effect of Cu(II). Overall, the adsorption capacity of aged TPU was higher than that of pristine TPU, which was due to the differences in morphological characteristics and functional groups. FTIR studies revealed that ester carbonyl and acylamino groups in the TPU may be involved in the adsorption of Cu(II) and OTC.

Long non-coding RNA MALAT1 modulate cell migration, proliferation and apoptosis by sponging microRNA-146a to regulate CXCR4 expression in acute myeloid leukemia.

OBJECTIVES: To investigate the role of Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) in acute myeloid leukemia (AML) and analyze the potential regulatory network of MALAT1/miR-146a/ CXCR4. METHODS: The expressions of MALAT1, miR-146a and CXCR4 were performed by qRT-PCR and Western Blot. We conducted trans-well assay, CCK-8 assay and flow cytometry to evaluate the migration, proliferation and apoptosis of AML cells. Also by using luciferase reporter assay, we investigated the interaction between miR-146a and MALAT1 or CXCR4. RESULTS: Firstly, MALAT1 and CXCR4 were upregulated while miR-146a was downregulated in AML patients compared with healthy controls. We observed a negative correlation between miR-146a and MALAT1 or CXCR4, but a positive correlation between MALAT1 and CXCR4 in AML patients. MALAT1 knockdown inhibited migration and proliferation but induced apoptosis of HL-60 cells. MALAT1 restrained miR-146a expression by acting as a ceRNA. miR-146a regulated HL-60 cells migration, proliferation and apoptosis by directly targeting CXCR4 expression. Finally, we found that CXCR4 expression was downregulated by MALAT1 knockdown and partially restored by miR-146a abrogation. CONCLUSIONS: Our results showed that MALAT1 regulates migration, proliferation and apoptosis by sponging miR-146a to regulate CXCR4 expression in AML cells, providing novel insights into the role of MALAT1 as a therapeutic target in AML.

[Sorption Behaviors of Copper Ions and Tetracycline on Microplastics in Aqueous Solution].

The interaction between microplastics, heavy metals, and antibiotics can lead to combined pollution, which could result in greater environmental damage. The pathway and mechanism of the interaction between microplastics, heavy metals, and antibiotics are the preconditions for evaluating the associated environmental risk; however, these are not well understood. As probe sorbates, the sorption behaviors of copper ions (Cu2+) and tetracycline (TC) on two microplastics [high density polyethylene (HPDE) and general-purpose polystyrene (GPPS)] in aqueous solution were investigated and the welding theory with relevant experimental results were discussed. The adsorption capacity of HDPE was greater than that of GPPS in a single Cu solution, whereas the reverse situation occurred in a single TC solution. Moreover, the adsorption capacity of the microplastics in a Cu2+-TC binary solution was larger than that in the single solutions. The pseudo-second-order kinetic models to describe the adsorption process were reasonable and the entire process could be divided into two phases:surface adsorption and internal diffusion. The Langmuir model provided a better fit of the data than did the Freundlich model. In the single solutions, the saturated adsorption amounts of Cu2+ and TC were 0.178 µmol·g-1 and 0.257 µmol·g-1, respectively, for GPPS, and 0.334 µmol·g-1 and 0.194 µmol·g-1, respectively, for HDPE. In the binary solution, the corresponding numerical values were 0.529 µmol·g-1 and 0.411 µmol·g-1, respectively, for GPPS and 0.471 µmol·g-1 and 0.341 µmol·g-1, respectively, for HDPE. The variations in the surface morphological characteristics and chemical functional groups were the main reasons for the difference in the adsorption behavior of microplastics. The variation of the pH of the adsorption system could change the existing forms and surface electrical properties of microplastics and adsorbed objects, and subsequently affected the equilibrium adsorption capacity. When the ambient temperature was in the range of 15 to 35℃, increasing the temperature was unfavorable for the adsorption process. Cu2+ and TC could produce a synergistic effect under the conditions of coexistence. The formation of complexes and bridging make Cu2+ and TC more easily adsorbed by microplastics.

Therapy-related acute promyelocytic leukemia with FMS-like tyrosine kinase 3-internal tandem duplication mutation in solitary bone plasmacytoma: A case report.

BACKGROUND: Therapy-related acute promyelocytic leukemia (t-APL) is a rare complication observed in solitary bone plasmacytoma (SBP), and SBP after radiotherapy evolving to APL harboring the FMS-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD) mutation has never been reported. Here, we present the first case reported until now. CASE SUMMARY: We describe a 64-year-old woman who presented with lumbar pain and was initially diagnosed with SBP. However, after one year of radiotherapy treatment, this patient experienced a long-standing bone-marrow-suppressive period and finally developed APL harboring the FLT3-ITD mutation, as confirmed by analyses of clinical features, bone marrow morphology, flow cytometry, cytogenetic examination, and molecular biology. On admission, the patient had disseminated intravascular coagulation and intracranial hemorrhage, and the peripheral blood and bone marrow smear displayed abundant abnormal promyelocytes. Unfortunately, she died when the definite diagnosis was made. CONCLUSION: The patient with t-APL harboring FLT3-ITD mutation evolving from SBP after radiotherapy had not been reported and had poor clinical outcomes. FLT3-ITD mutation in t-APL may be a potential pathogenesis of leukemogenesis. We should consider the potential risk of secondary neoplasms in SBP patients after radiotherapy.

Chinese Medicine Treatment on Graft-Versus-Host Disease after Allogeneic Hematopoietic Stem Cell Transplantation.

Graft-versus-host disease (GVHD) is the most common complication after allogeneic hematopoietic stem cell transplantation, and also an important factor affecting the survival and quality of life in patients after transplantation. Currently, immunosuppressive therapy is commonly used for GVHD, but the curative effect is not ideal. How to effectively prevent and treat GVHD is one of the difficulties to be solved urgently in the field of transplantation. In this paper, we summarize the latest progress in pathogenesis, prevention and treatment of GVHD with Chinese medicine (CM). We hope it will provide ideas and methods for exploring the mechanism and establishing a new comprehensive therapy for GVHD with CM.

Panaxdiol Saponins Component Promotes Hematopoiesis and Modulates T Lymphocyte Dysregulation in Aplastic Anemia Model Mice.

OBJECTIVE: To investigate the potential efficacy of panaxadiol saponins component (PDS-C) in the treatment of aplastic anemia (AA) model mice. METHODS: Totally 70 mice were divided into 7 groups as follows: normal, model, low-, medium-, high-dose PDS-C (20, 40, 80 mg/kg, namely L-, M-, H-PDS-C), cyclosporine (40 mg/kg), and andriol (25 mg/kg) groups, respectively. An immune-mediated AA mouse model was established in BALB/c mice by exposing to 5.0 Gy total body irradiation at 1.0 Gy/min, and injecting with lymphocytes from DBA mice. On day 4 after establishment of AA model, all drugs were intragastrically administered daily for 15 days, respectively, while the mice in the normal and model groups were administered with saline solution. After treatment, the peripheral blood counts, bone marrow pathological examination, colony forming assay of bone marrow culture, T lymphocyte subpopulation analysis, as well as T-bet, GATA-3 and FoxP3 proteins were detected by flow cytometry and Western blot. RESULTS: The peripheral blood of white blood cell (WBC), platelet, neutrophil counts and hemoglobin (Hb) concentration were significantly decreased in the model group compared with the normal group (all P<0.01). In response to 3 dose PDS-C treatment, the WBC, platelet, neutrophil counts were significantly increased at a dose-dependent manner compared with the model group (all P<0.01). The myelosuppression status of AA was significantly reduced in M-, H-PDS-C groups, and hematopoietic cell quantity of bone marrow was more abundant than the model group. The colony numbers of myeloid, erythroid and megakaryocytic progenitor cells in the model group were less than those of the normal mice in bone marrow culture, while, PDS-C therapy enhanced proliferation of hematopoietic progenitor cells by significantly increasing colony numbers (all P<0.01). Furthermore, PDS-C therapy increased peripheral blood CD3+ and CD3+CD4+ cells and reduced CD3+CD8+ cells (P<0.05 or P<0.01). Meanwhile, PDS-C treatment at medium- and high doses groups also increased CD4+CD25+FoxP3+ cells, downregulated T-bet protein expression, and upregulated GATA-3 and FoxP3 protein expressions in spleen cells (P<0.05). CONCLUSION: PDS-C possesses dual activities, promoting proliferation hematopoietic progenitor cells and modulating T lymphocyte immune functions in the treatment of AA model mice.

Effects of panaxadiol saponins component as a new Chinese patent medicine on proliferation, differentiation and corresponding gene expression profile of megakaryocytes.

OBJECTIVE: To investigate the effects of panaxadiol saponins component (PDS-C) isolated from total saponins of panax ginseng on proliferation, differentiation and corresponding gene expression profile of megakaryocytes. METHODS: Bone marrow culture of colony forming assay of megakaryocytic progenitor cells (CFU-MK) was observed for the promoting proliferation mediated by PDS-C, and differentiation of megakaryocytic blasts caused by PDS-C was analyzed with flow cytometry in CHRF-288 and Meg-01 cells, as well as proliferation, differentiation-related genes expression profile and protein expression levels were detected by human gene expression microarray and western blot. RESULTS: In response to PDS-C 10, 20 and 50 mg/L, CFU-MK from 10 human bone marrow samples was increased by 28.9%±2.7%, 41.0%±3.2% and 40.5%±2.6% over untreated control, respectively (P <0.01, each). Flow cytometry analysis showed that PDS-C treated CHRF-288 cells and Meg-01 cells significantly increased in CD42b, CD41, TSP and CD36 positive ratio, respectively. PDS-C induced 29 genes up-regulated more than two-fold commonly in both cells detected by human expression microarray representing 4000 known genes. The protein expression levels of ZNF91, c-Fos, BTF3a, GATA-1, RGS2, NDRG2 and RUNX1 were increased with western blot in correspond to microarray results. CONCLUSION: PDS-C as an effective component for hematopoiesis, play the role to enhance proliferation and differentiation of megakaryocytes, also up-regulated expression of proliferation, differentiation-related genes and proteins in vitro.

Treatment of severe aplastic anemia by immunosuppressor anti-lymphocyte globulin/anti-thymus globulin as the chief medicine in combination with Chinese drugs.

OBJECTIVE: To study the therapeutic effect of combined therapy with Chinese drugs and immuno-suppressors, mainly anti-lymphocyte globulin/anti-thymus globulin (ALG/ATG), for the treatment of severe aplastic anemia (SAA), the efficacy associated factors and adverse effects as well. METHODS: A retrospective analysis was conducted on 65 patients with SAA treated by combined therapy which was supplemented with cyclosporin A, androgen, hematopoietic growth factor, etc. RESULTS: Of the 57 patients followed-up, 26 (45.6%) were basically cured, 15 (26.3%) remitted, and 8 (14.0%) improved markedly, the total effective rate being 85.9%. By separately comparing with a single item of clinical data, it was shown that the therapeutic effectiveness was correlated, to a certain extent, with age, illness duration, neutrophil count, and bone marrow proliferation in patients before treatment, as well as with infection that occurred in the follow-up period. It was obviously higher in patients with peripheral neutrophil count > 0.5 x 10 10(9)/L (P<0.05). Various degrees of serum sickness-like reactions occurred in the treatment of 36 patients, including fever in 36 (63.2%), skin rash in 8 (14.0%), and musculoskeletal pain in 5 (8.8%). CONCLUSIONS: The therapeutic effect of combined therapy with Chinese drugs and ALG/ATG in treating SAA could be affirmed, showing some superiority as compared with Western medicine alone. The patients' age, duration of illness, neutrophil count, and bone marrow proliferation before treatment, and degree of infection that occurred could affect the therapeutic efficacy to a certain extent. Adverse reactions resulting from the combined therapy are less, showing the toxicity reducing and effect enhancing action of Chinese drugs.