[Clinical Characteristics and Prognosis of Myelodysplastic Syndromes Patients with RUNX1 Gene Mutation].

OBJECTIVE: To investigate the clinical characteristics and survival analysis of myelodysplastic syndromes (MDS) with RUNX1 gene mutation. METHODS: Clinical data of 177 newly diagnosed MDS patients admitted to the Department of Hematology, the Second Affiliated Hospital of Air Force Military Medical University from October 1, 2015 to October 31, 2022 were retrospectively analyzed. Gene mutation detection was performed by second-generation sequencing technology, and clinical characteristics and prognosis of patients with RUNX1 gene mutation were analyzed. RESULTS: A total of 30 cases (16.95%) of RUNX1 gene mutations were detected, including 15 missense mutations (50.0%), 9 frameshift deletion mutations (30.0%), 4 splice site mutations (13.3%), 1 insertion mutation (3.3%), and 1 nonsense mutation (3.3%). Patients with RUNX1 mutations had a median age of 68.5 years at diagnosis (range: 62.25-78.50 years old). There were no significantly differences between RUNX1 mutations and wild type patients in age distribution, gender, peripheral blood white blood cell count, hemoglobin level, bone marrow and peripheral blood blasts ratio, IPSS-R cytogenetics, IPSS-R stage, etc. (P >0.05). However, there were statistically significant differences in platelet count and whether complicated karyotype. Compared with patients without RUNX1 gene mutation, patients with RUNX1 gene mutation had lower platelet count (P =0.018), and were less likely to have complicatedkaryotype at initial diagnosis (P =0.01). Cox proportional hazards model analysis showed that when other covariates remained unchanged, the higher the platelet count, the better the survival of patients (HR=0.995, 95%CI : 0.990-0.999, P =0.036); In the IPSS-M prognostic stratification, keeping other covariates unchanged, the risk of progression or death of myelodysplastic syndrome was significantly lower in the medium to high-risk and low-risk groups compared with the high-risk group (HR=0.149, 95%CI : 0.031-0.721, P =0.018; HR=0.026, 95%CI : 0.003-0.234, P =0.001). Survival analysis showed that MDS patients with RUNX1 gene mutation had worse overall survival time (P < 0.001). Patients with RUNX1 mutation had worse OS than non-mutation patients in the early WHO group. RUNX1 mutation and IPSS-M risk stratification mean OS and mean LFS were worse in low-risk patients than in non-mutated patients. CONCLUSION: RUNX1 gene mutation is an adverse prognostic factor in MDS patients, especially in the IPSS-M prognosis stratification group of low-risk, medium-low risk, medium-high risk and WHO classification of early patients.

Adsorption performance and mechanism of pectin modified with ß-cyclodextrin for Zn2+ and Cu2.

Removing heavy metals from aqueous solutions has drawn more and more attentions these years because of their serious global health challenge to human society. To develop an adsorbent with green, stable and high-efficiency for adsorption of heavy metals, pectin ß-cyclodextrin composite was successfully prepared and used for Zn2+ and Cu2+ adsorption for the first time. Various variables that influence the adsorption performance were explored, and the optimal adsorption conditions were determined. According to the pseudo-second-order kinetic model, the adsorption process of Zn2+ and Cu2+ by the adsorbent was mainly chemical adsorption. The adsorbent adsorption process was an exothermic and non-spontaneous process. According to the Langmuir isotherm model, the maximum adsorption capacity was 12.51 ± 0.33 and 24.98 ± 0.23 mg/g for Zn2+ and Cu2+, respectively. The FTIR, EDX and XPS results revealed that the main mechanisms of removing pollutants by adsorbent were ion exchange and coordination. In addition, electrostatic attraction and chelation were present in the adsorption process. After five adsorption desorption cycles, the pectin ß-cyclodextrin composite adsorbent still exhibited adsorption and regeneration capabilities. This study provides a low-cost, effective and simple method for preparation of modified pectin, which has excellent application potential in the removal of heavy metal ions from wastewater.

Efficacy and safety of cladribine in combination with busulfan and cyclophosphamide as an intensive conditioning regimen preceding allogeneic hematopoietic stem cell transplantation in relapsed or refractory acute myeloid leukemia.

BACKGROUND: Cladribine, an analogue of deoxyadenosine, is used for therapy of hematological malignancies. Cladribine-containing regimen has been recommended as a rescue therapy for relapsed or refractory (R/R) acute myeloid leukemia (AML). Its combination with busulfan plus cyclophosphamide (BuCy), as an intensive conditioning regimen prior to allogeneic hematopoietic stem cell transplantation (allo-HSCT), requires more clinical evidence. This study aimed to explore the efficacy and safety of cladribine plus BuCy administered as an intensive conditioning regimen before allo-HSCT in R/R AML patients. METHODS: Twenty-three R/R AML patients, who underwent cladribine plus BuCy intensive conditioning regimen before allo-HSCT, were retrospectively analyzed. The median (range) follow-up duration time of observation was 0.73 (0.08-2.69) years. RESULTS: The median (range) returned levels of mononuclear cells were 11.5 (6.1-18.5) x 108/kg and CD34+ cells were 5.5 (3.5-9.3) x 106/kg. The median (range) time of platelet reconstitution was 13.0 (9.0-21.0) days and neutrophil reconstitution was 14.0 (11.0-26.0) days. The incidence of conditioning regimen related toxicity (CRRT) affected 69.6% of patients; all CRRT-affected patients had grade I-II symptoms, including gastrointestinal tract (39.1%), oral cavity (26.1%), liver (8.7%), and kidney (4.3%) CRRTs. The incidence of acute graft-versus-host disease (GVDH) included 30.4% among all patients with 4.3% of grade III-IV acute GVHD, and 34.8% of chronic GVHD. During the follow-up period, 4 (17.4%) patients relapsed, and 6 (26.1%) patients died (cause of death: disease relapse, n = 3; infection, n = 2; GVHD, n = 1). The 1-year and 2-year accumulating event-free survival rates were 66.3% and 53.1%, respectively. The 1-year accumulating overall survival rate was 74.7% and 2-year survival rate was 64.0%. CONCLUSION: Cladribine plus BuCy intensive conditioning regimen before allo-HSCT exhibits favorable treatment efficacy with acceptable toxicity in R/R AML patients.

Impact of a novel prognostic model on allogeneic hematopoietic stem cell transplantation outcomes in patients with CMML.

Chronic myelomonocytic leukemia (CMML) is a clonal hematopoietic stem cell malignancy, and allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only curable treatment. The outcomes after transplant are influenced by both disease characteristics and patient comorbidities. To develop a novel prognostic model to predict the post-transplant survival of CMML patients, we identified risk factors by applying univariable and multivariable Cox proportional hazards regression to a derivation cohort. In multivariable analysis, advanced age (hazard ratio [HR] 3.583), leukocyte count (HR 3.499), anemia (HR 3.439), bone marrow blast cell count (HR 2.095), and no chronic graft versus host disease (cGVHD; HR 4.799) were independently associated with worse survival. A novel prognostic model termed ABLAG (Age, Blast, Leukocyte, Anemia, cGVHD) was developed and the points were assigned according to the regression equation. The patients were categorized into low risk (0-1), intermediate risk (2, 3), and high risk (4-6) three groups and the 3-year overall survival (OS) were 93.3% (95%CI, 61%-99%), 78.9% (95%CI, 60%-90%), and 51.6% (95%CI, 32%-68%; p < .001), respectively. In internal and external validation cohort, the area under the receiver operating characteristic (ROC) curves of the ABLAG model were 0.829 (95% CI, 0.776-0.902) and 0.749 (95% CI, 0.684-0.854). Compared with existing models designed for the nontransplant setting, calibration plots, and decision curve analysis showed that the ABLAG model revealed a high consistency between predicted and observed outcomes and patients could benefit from this model. In conclusion, combining disease and patient characteristic, the ABLAG model provides better survival stratification for CMML patients receiving allo-HSCT.

Revealing the mechanisms of polypyrrole (Ppy) enhancing methane production from anaerobic digestion of waste activated sludge (WAS).

Anaerobic digestion (AD) is a promising method for treating waste activated sludge (WAS), but the low methane yield limits its large-scale application. The addition of conductive nanomaterials has been demonstrated to enhance the activity of AD via promoting the direct interspecies electron transfer (DIET). In this study, novel conductive polypyrrole (Ppy) was prepared to effectively improve the AD performance of WAS. The results showed that the accumulative methane production was enhanced by 27.83% by Ppy, with both acidogenesis and methanogenesis being efficiently accelerated. The microbial community analysis indicated that the abundance of bacteria associated with acidogenesis process was significantly elevated by Ppy. Further investigation by metatranscriptomics revealed that fadE and fadN genes (to express the key enzymes in fatty acid metabolism) were highly expressed in the Ppy-driven AD, suggesting that Ppy promoted electron generation during acid production. For methanogenesis metabolism, genes related to acetate utilization and CO2 utilization methanogenesis were also up-regulated by Ppy, illustrating that Ppy facilitates the utilization of acetate and electrons by methanogenic archaea, thus potentially promoting the methanogenesis through DIET.

[Clinical Outcomes and Prognostic Factors of Allogeneic Hematopoietic Stem Cell Transplantation in the Treatment of Refractory/Relapsed Acute Myeloid Leukemia].

OBJECTIVE: To investigate the clinical outcomes and prognostic factors of refractory/relapsed acute myeloid leukemia (AML) patients who received allogeneic hematopoietic stem cell transplantation (allo-HSCT). METHODS: The clinical data of 80 refractory/relapsed AML patients who received allo-HSCT from December 2013 to June 2020 were retrospectively analyzed, including the overall survival (OS) rate, disease-free survival (DFS) rate, relapse rate, incidence of transplant-related mortality (TRM), and the related risk factors were explored. RESULTS: Hematopoietic reconstitution was obtained in all 80 patients after transplantation, the 3-year OS and DFS rates were (48.8±6.3)% and (40.8±6.7)%, respectively. The 3-year cumulative incidence of relapse and TRM were 33.8% (95%CI: 0.254-0.449) and 15.0%(95%CI: 0.114-0.198), respectively. Univariate analysis showed that non-remission (NR) status before transplantation, DNMT3A R882 mutations and grade II-IV acute graft-versus-host disease (aGVHD) had negative effects on OS and DFS. Multivariate analysis indicated that the DNMT3A R882 mutations and grade II-IV aGVHD were independent risk factors for OS (HR=0.253, 95%CI: 0.092-0.695, P=0.008; HR=5.681, 95%CI: 2.101-15.361, P=0.001) and DFS (HR=0.200, 95%CI: 0.071-0.569, P=0.003; HR=7.117, 95%CI: 2.556-19.818, P<0.001). The 3-year cumulative incidence of relapse was 71.4%(95%CI: 0.610-0.836) in genetic high-risk group, which was higher than 23.3%(95%CI: 0.147-0.370) in intermediate-risk group and 23.5%(95%CI: 0.127-0.437) in favorable-risk group (P=0.006). CONCLUSION: Allo-HSCT is an effective and safe choice for refractory/relapsed AML patients. DNMT3A R882 mutations and grade II-IV aGVHD are negative prognostic factors of allo-HSCT for refractory/relapsed AML patients.

High Sensing Performance Toward Acetone Vapor Using TiO2 Flower-Like Nanomaterials.

For real-application gas sensors, high performances (response, selectivity, response/recovery time and stability) are demanded. An effective strategy is applying nanomaterials in gas sensors. In this study, the anatase TiO2 flower-like nanomaterials (FLNMs) are prepared through a one-step hydrothermal method which exhibit high-performance toward acetone vapor. TiO2 FLNMs sensors property are characterized at optimal working temperature of 330 °C with selectivity (acetone), response (S = 33.72 toward 250 ppm acetone), linear dependence (R2 = 0.9913), response/recovery time (46/24 s toward 250 ppm acetone) and long-term stability (30 days). These demonstrate that TiO2 FLNMs get a high performance for acetone sensor. Moreover, the limit of detection of acetone is 0.65 ppm which is lower than that of exhaled air for diabetes (0.8 ppm), indicating that TiO2 FLNMs gas sensor gets potential application in medical diagnosis.

The characterization of a novel magnetic biochar derived from sulfate-reducing sludge and its application for aqueous Cr(â ¥) removal through synergistic effects of adsorption and chemical reduction.

Removal of heavy metals from the aqueous environment via physiochemical adsorption always remains a great challenge owing to the slow kinetics and low removal capacity for the conventional adsorbent. In this study, the sulfate-reducing bacteria (SRB)-rich anaerobic sludge was pyrolyzed for the preparation of magnetic biochar, i.e. SBC-20-500 (SBC: sulfate-reducing sludge-based biochar; 20 denotes the biochar dosage, namely 8 g dried sludge in 400 mL iron solution which is equal to 20 g/L; 500 represents the pyrolysis temperature, i.e. at 500 °C) with tunable pore structure and surface properties towards efficient removal of chromium (Cr (Ⅵ)). The characterization revealed that magnetic biochar SBC-20-500 exhibited higher surface area and larger pore volume compared to non-magnetic SBC-500. Batch experiments on Cr (Ⅵ) removal were performed under different biochar dosages, pH values, initial Cr (Ⅵ) concentrations and temperatures. The results illustrated that magnetic biochar demonstrated much larger Cr (Ⅵ) adsorption capacity with qe of 5.3585 mg/g as compared to non-modified one (qe = 0.7206 mg/g). The maximum Cr (Ⅵ) removal efficiency of SBC-20-500 reached approximately 93.7% within 24 h under the conditions of pH = 3.0, biochar dosage = 0.8 g and initial Cr (Ⅵ) concentration = 50 mg/L. The kinetic and isotherm fitting results suggested that the pseudo-second-order kinetic and Langmuir isotherm model were more suitable for describing the adsorption behavior of Cr (Ⅵ) by SBC-20-500. The XPS and FTIR results confirmed that chemical reduction of Cr (Ⅵ) to Cr (Ⅲ) also played a role in Cr (Ⅵ) removal in the presence of SBC-20-500. Moreover, the Cr (Ⅵ) removal capacity could still achieve 3.50 mg/g even after five adsorption-desorption cycles, indicating the satisfactory reusability of the as-prepared biochar. The results of this study may provide a win-win approach for simultaneous resource recovery from the wasted sulfate-reducing sludge (SRS) and highly-efficient remediation of Cr (Ⅵ)-contaminated environment.

CdS Micrometer Hollow Spheres for Detecting Alcohols Except Methanol with Strong Anti-interference Ability.

Cadmium sulfide micrometer hollow spheres (CdS MHs) were fabricated by a hydrothermal method. The performance of the CdS MHs sensor was evaluated by detecting volatile organic compounds such as methanol, ethanol, 1-propanol, isopropanol, n-butanol, iso-butyl alcohol, iso-amyl alcohol, acetone, and xylene. It was found that the optimum working temperature of the CdS MHs sensor is 190 °C. The response of the CdS MHs can reach 27.4-100 ppm ethanol and reach 84.55-100 ppm isopropanol. Comparing the response to pure 5 ppm isopropanol (iso-amyl alcohol) with the mixture of 5 ppm isopropanol (iso-amyl alcohol) and 50 ppm acetone or 5 ppm isopropanol (iso-amyl alcohol) and 50 ppm methanol, the relative deviation was -1.33% (-7.11%) or -6.19% (9.20%). It suggested that the CdS MHs sensor had a strong anti-interference ability to methanol and acetone and is suitable for detecting alcohols except methanol. Therefore, the CdS MHs sensor had good response and is a promising alcohol detection material.

Ultra-High Response Detection of Alcohols Based on CdS/MoS2 Composite.

Hybrid CdS/MoS2 with branch and leaf shaped structures are successfully synthesized by hydrothermal method. It is applied to detect volatile organic compounds, a basic source of indoor air pollution with deleterious effects on the human health. The sensor based on CdS/MoS2 displays an outstanding response to alcohols among numerous gases. Their response to 100 ppm ethanol and isopropanol reaches 56 and 94, respectively. Benefiting from the dendrite-like biomimetic structure and synergy effect of CdS and MoS2, the sensor exhibits higher response than traditional gas sensor. For multiple alcohols, the limit of detection reached ppb level. In addition, by comparing the response of ethanol, isopropanol, isoamyl alcohol and their mixtures with acetone and methanal, a strong resistance interference is observed. This work proved that the modified detector holds broad promise in the detection of alcohols.

Recyclable Ag-Deposited TiO2 SERS Substrate for Ultrasensitive Malachite Green Detection.

An ultrasensitive Ag-deposited TiO2 flower-like nanomaterial (FLNM) surface-enhanced Raman scattering (SERS)-active substrate is synthesized via a hydrothermal method, and Ag nanoparticles (NPs) are deposited through electron beam evaporation. Malachite green (MG), which is widely used in aquaculture, is employed to assess the surface-enhanced Raman scattering (SERS) properties of TiO2/Ag FLNMs. They exhibit ultrasensitivity (limit of detection (LOD) of MG reaches 4.47 × 10-16 M) and high reproducibility (relative standard deviations (RSDs) are less than 13%); more importantly, the TiO2/Ag FLNMs are recyclable, as enabled by their self-cleaning function due to TiO2 photocatalytic degradation. Their recyclability is achieved after three cycles and their potential application is examined in the actual system. Finite difference time domain (FDTD) simulations and the charge-transfer (CT) mechanism further prove that the excellent SERS properties originate from localized surface plasmon resonance (LSPR) of Ag NPs and the coupling field between Ag and TiO2 FLNMs. Therefore, TiO2/Ag FLNMs show promising application in aquaculture.

[Clinical Efficacy of Autologous Hematopoietic Stem Cell Transplantation for Patients with Diffuse Large B-Cell Lymphoma].

OBJECTIVE: To compare the clinical efficacy of first-line and salvage autologous hematopoietic stem cell transplantation (auto-HSCT) in the treatment of patients with diffuse large B-cell lymphoma (DLBCL). METHODS: The clinical data of 30 patients with DLBCL aged≤60 years old were retrospectively analyzed, and the patients were divided into first-line auto-HSCT group (15 cases) and salvage auto-HSCT group (refractory relapsed patients, 15 cases) according to the timing of transplantation, and the efficacy was analyzed. Anyone of the factors must be followed in patients receiving first-line HSCT: aaIPI score≥2 points, Ann-Arbor stage III-IV, large mass (diameter≥10 cm) or double expression of c-myc/BCL-2. RESULTS: The median follow-up time for all patients after transplantation was 26 (3-103) months. Until the end of follow-up, 23 patients survived and 7 patients died. All the 7 dead patients with multiple organ failure due to the relapse and disease progression. The median survival time of 7 dead patients from transplantation to death was 6 (3-11) months. Among the 15 patients in the first-line auto-HSCT group, there were 2 patients relapsed (13.3%), 1 dead (6.7%), 14 patients survived [overall survival (OS) rate was 93.3%]. Among the 15 patients treated with salvage auto-HSCT, 6 patients died due to disease progression or relapse (40%), 9 cases survived (OS rate was 60%). There was a statistically significant difference in the mortality of patients between the two groups (6.7% vs 40%, P=0.006). The 3-year PFS and OS rates of patients in first-line auto-HSCT group were both 93.3%. The 3-year PFS and OS of patients in salvage auto-HSCT group were 58.7% and 59.2%. The 3-year OS and PFS of patients in the first-line auto-HSCT group were significantly higher than those in the salvage auto-HSCT group (P=0.03, P=0.04). The bone marrow suppression was the most common adverse complication and all patients showed grade III-IV granulocytopenia. Non-hematological adverse reactions were mainly gastrointestinal adverse reactions and oral mucositis. There was no statistically significant difference in adverse reactions between the two groups. CONCLUSION: First-line auto-HSCT can be used as a consolidation treatment for DLBCL patients with poor prognostic factors. Auto-HSCT can further improve the prognosis of salvage chemotherapy-sensitive patients with refractory relapsed DLBCL.

Enhanced photodegradation of doxycycline (DOX) in the sustainable NiFe2O4/MWCNTs/BiOI system under UV light irradiation.

In this study, a magnetic NiFe2O4/MWCNTs/BiOI composite were fabricated and applied for enhanced and sustainable photocatalytic degradation of doxycycline (DOX) under UV light irradiation. The as-synthesized material was characterized by a series of techniques and its photocatalytic property was assessed via a couple of batch tests. With the pH at 3.0 and NiFe2O4/MWCNTs/BiOI loading of 1.5 g L-1, the DOX degradation (at 45 mg L-1) efficiency could achieve 92.18% with the reaction rate constant k of 0.0072 min-1. The high mineralization of DOX suggests the strong oxidation of both the parent pollutant and the intermediary products in the ternary catalyst system. DRS spectra indicated that compared with BiOI, the introduction of NiFe2O4 and MWCNTs reduces the band gap energy of the NiFe2O4/MWCNTs/BiOI. The quenching test illustrates that h+, OH and O2- all functioned in the developed photocatalytic system, where O2- and h+ play the dominant roles in DOX degradation. The more efficient electron-h+ separation and more oxidizing species induced by UV light resulted in the significant improvement of DOX abatement in the developed coupling system compared with that on either BiOI or NiFe2O4/MWCNTs. The magnetic property of NiFe2O4/MWCNTs/BiOI enables its easy separation of the solid catalyst from the reaction solution and the sustainable application in the photocatalysis. Based on the intermediates of DOX decomposition identified by UPLC-MS, the possible degradation routes were proposed accordingly.

Achieving rapid thiosulfate-driven denitrification (TDD) in a granular sludge system.

Sulfur-oxidizing bacteria (SOB) can drive a high level of autotrophic denitrification (AD) activity with thiosulfate (S2O32-) as the electron donor. However, the slow growth of SOB results in a low biomass concentration in the AD reactor and unsatisfactory biological nitrogen removal (BNR). In this study, our goal was to establish a high-rate thiosulfate-driven denitrification (TDD) system via sludge granulation. Granular sludge was successfully cultivated by increasing the nitrogen loading rate stepwise in thiosulfate-oxidizing/nitrate-reducing conditions in an upflow anaerobic blanket reactor. In the mature-granular-sludge reactor, a nitrate removal rate of 280 mg N/L/h was achieved with a nitrate removal efficiency of 97.7%±1.0% at a hydraulic retention time of only 15 minutes, with no nitrite detected in the effluent. Extracellular polymeric substance (EPS) analysis indicated that the proteins in loosely bound and tightly bound EPS were responsible for maintaining the compact structure of the TDD granular sludge. The dynamics of the microbial-community shift were identified by 16S rRNA high-throughput pyrosequencing analysis. The Sulfurimonas genus was found to be enriched at 74.1% of total community and may play the most critical role in the high-rate BNR. The batch assay results reveal that no nitrite accumulation occurred during nitrate reduction because the nitrate reduction rate (75.90±0.67 mg N/g MLVSS/h) was almost equal to the nitrite reduction rate (66.06±1.28 mg N/g MLVSS/h) in the thiosulfate-driven granular sludge reactor. The results of this study provide support for the establishment of a high-rate BNR system that maintains its stability with a low sludge yield.

[Comparison of Frontline Haploidentical Hematopoietic Stem Cell Transplantation and Salvage Haploidentical Hematopoietic Stem Cell Transplantation for Patients with Severe Aplastic Anemia].

OBJECTIVE: To compare the clinical efficacy between frontline haplo-identical hematopoietic stem cell transplantation (haplo-HSCT) and salvage haplo-HSCT for patients with severe aplastic anemia (SAA). METHODS: A total of 39 patients with severe aplastic anemia or very severe aplastic anemia from May 1st, 2013 to December 31st, 2018 were analyzed retrospectively. All of them underwent bone marrow + peripheral blood hemopoietic stem cell transplantation. There were 20 cases who accepted frontline haplo-HSCT for a median course of 1 (1-3) month, and 19 cases who accepted salvage haplo-HSCT for a median course of 72 (6-168) months. Conditioning regimen: 22 cases received Flu/Cy+ATG, and 17 cases received Bu/Cy+ATG. RESULTS: The time of hematopoietic reconstitution, infection rate, and grade I-Ⅱ and Ⅲ-Ⅳ acute/chronic graft versus host disease showed no statistically significance between the frontline haplo-HSCT group and the salvage haplo-HSCT group. In the frontline haplo-HSCT group, 1 case (5%) failed in second engraftment, in the salvage haplo-HSCT group 2 cases (10.5%) failed in primary engraftment and 4 cases (21.1%) in second engraftment. The incidence of engraftment failure was higher in the salvage haplo-HSCT group than that in the frontline haplo-HSCT group (P=0.04). The median time of follow-up after allo-HSCT was 45 months (ranging from 3 to 92). The mortality was 10% (2/20) in the frontline haplo-HSCT group, and 42.1% (8/19) in the salvage haplo-HSCT group. The estimated 5-year failure-free survival rate (FFS) of the frontline haplo-HSCT group was higher than that of the salvage haplo-HSCT group (90% vs 57.4%) (P=0.02). CONCLUSION: The frontline haplo-HSCT is an effective and safe approach for the patients with severe aplastic anemia who lack a HLA-matched sibling donor.

[Correlation between Plasma microRNA Expression and Acute Graft-Versus-Host Disease after Allogeneic Hematopoietic Stem Cell Transplantation].

OBJECTIVE: To investigate the microRNA (miRNA) expression in plasma of patients with aGVHD and without aGVHD after allo-hematopoietic stem cell transplantation (allo-HSCT). METHODS: The miRNAs (miR-423, mirR199a-3p, miR93*, miR377) expression levels in peripheral blood plasma of 25 patients before and after allo-HSCT were detected by real-time PCR. RESULTS: miR-423, miR199a-3p and miR-93* in aGVHD group were significantly upregulated (P<0.05); miR-377 expression was not significantly different between aGVHD and non-aGVHD (P>0.05). CONCLUSION: The expression of miR-423, miR-199a-3p, miR-93* are upregulated in aGVHD group, which can be used as biomarkes to monitor and to diagnose aGVHD.

Low expression of circulating microRNA-328 is associated with poor prognosis in patients with acute myeloid leukemia.

BACKGROUND: Dysregulation of circulating miR-328 has been identified in several tumors and is associated with prognosis of patients. However, the expression pattern of miR-328 and the impact on prognosis has not yet been studied in acute myeloid leukemia (AML). The purpose of this study is to investigate the expression status of miR-328 and its clinical significance in AML patients. METHODS: RNA was extracted from plasma of 176 patients with newly diagnosed AML and 70 healthy volunteers. The miR-328 expression was examined by Realtime quantitative PCR. The association of circulating miR-328 expression with clinicopathological factors and prognosis of AML patients was statistically analyzed. RESULTS: The expression of miR-328 was significantly downregulated in AML patients (median value 22.99, range: 3.63-242.0) compared with those of healthy controls (median value 89.17, range: 12.05-397.7; P < 0.001), and miR-328 expression was markedly increased in patients after treatment than before (23.40 ± 1.76 vs. 46.61 ± 3.83, P < 0.001). Moreover, low levels of miR-328 were associated with a higher white blood cell count and BM blast count (P = 0.026 and P = 0.003, respectively), and lower hemoglobin and platelet count (P = 0.004 and P = 0.022, respectively). Patients with low miR-328 expression had a relatively poor overall survival (P = 0.022) and shorter relapse-free survival (P = 0.008) than those with high miR-328 expression. In addition, low miR-328 expression was an independent prognostic factors for both OS (P = 0.017) and RFS (P = 0.023). CONCLUSIONS: Circulating miR-328 downregulation is a common event and is associated with poor clinical outcome in AML patients.

Soluble extracellular domains of human SIRPα and CD47 expressed in Escherichia coli enhances the phagocytosis of leukemia cells by macrophages in vitro.

Signal regulatory protein (SIRP) α, a transmembrane protein belonging to the immunoglobulin superfamily, is a receptor for CD47. The interaction between SIRPα and CD47 plays an important role in regulating the phagocytosis of leukemia cells and leukemia stem cells (LSCs) by macrophages. Blocking antibodies against CD47 have been shown to promote phagocytosis of LSCs by macrophages. Here, we consider an alternative way to interrupt the interaction between CD47 and SIRPα. We expressed the extracellular domains of the human SIRPα (hSIRP(ext)) and the human CD47 (hCD47(ext)) in Escherichia coli as Trx fusion proteins, and purified them by using affinity chromatography. We show that the purified fusion protein Trx-SIRP(ext) could interact in vitro with Trx-hCD47(ext). Moreover, Trx-SIRP(ext) could effectively bind to Jurkat T-ALL cells, which expressed CD47 at a high level. CD47(ext), on the other hand, bound to human macrophages. In vitro phagocytosis assay showed that these fusion proteins could enhance the phagocytosis of Jurkat cells by macrophage, with Trx-hSIRP(ext) showed a higher efficiency than Trx-CD47(ext). These results indicated that the soluble Trx-hSIRP(ext) and Trx-CD47(ext) polypeptides could be alternative molecules to interrupt CD47-SIRPα interaction between leukemia cells and macrophages, and might be potentially useful for the targeted therapy of leukemia.