OBJECTIVE:To investigate the effects of nutritional supportive therapy on hematopoietic stem cell transplantation (HSCT) patients and to analyze its relationship with post-transplant hematopoietic reconstitution, acute graft-versus-host disease (aGVHD). METHODS:The clinical data of 76 HSCT patients in our hospital were collected from November 2020 to November 2023, included 46 cases in the nutritional intervention group and 30 in the non-intervention group. After assessing the nutritional status of the intervention group, the five-step therapy principle was followed to implement refined nutritional support treatment, the total daily energy requirement by the patients was calculated based on 25-30 kcal/(kg·d) from the first day of pretreatment to 90 days post-transplantation, followed up until March 2024. The nutritional indices and clinical outcomes of both groups pre-transplant and at 30, 60, and 90 days post-transplant was observed. RESULTS:At 30 days and 60 days after transplantation, the total protein level in the intervention group was higher than before transplantation (P<0.05). At 30 days, 60 days, and 90 days after transplan-tation, the triglyceride levels in both groups were higher than before transplantation (P<0.05). At 30 days and 90 days after transplantation, the HDL-C level in the intervention group was lower than before transplantation (P<0.05). At 60 days after transplantation, the BMI level in the intervention group was higher than that in the non-intervention group (P<0.05). At 30, 60, and 90 days after transplantation, the albumin level in the intervention group was higher than that in the non-intervention group (P<0.05). At 30 days after transplantation, the prealbumin level in the intervention group was higher than that in the non-intervention group (P<0.05). At 30 days and 60 days after transplantation, the total protein level in the intervention group was higher than that in the non-intervention group (P<0.05). At 60 days after transplantation, the low density lipoprotein cholesterol (LDL-C) and triglyceride levels in the intervention group were lower than those in the non-intervention group (P<0.05). At 30 days after transplantation, the HDL-C level in the intervention group was lower than that in the non-intervention group (P<0.05). Time of hematopoietic recons-truction after transplantation: the days for granulocyte reconstitution in the intervention group were earlier than those in the non-intervention group (P<0.05), while there was no statistically significant difference in the number of days for megakaryocyte reconstitution between the two groups (P＞0.05). At 30 days after transplantation, the level of soluble growth stimulus expression gene 2 protein (sST2) in the intervention group was significantly lower than that in the non-intervention group (P<0.05). The level of soluble interleukin-2 receptor (sCD25) in the intervention group at 60 days after transplantation was lower than that at 30 days after transplantation (P<0.05). At different time points after transplantation, there was no statistically significant differences between the two groups in regenerative lslet derived protein 3 alpha (REG3α), soluble tumor necrosis factor receptor 1 (sTNFR1), and elastase inhibitory factor (Elafin) (P＞0.05). CONCLUSION:The implementation of nutritional support therapy not only ameliorates malnutrition and hastens granulopoiesis, but also mitigates the risk of aGVHD and improves the prognosis of patients undergoing hematopoietic stem cell transplantation.

ObjectiveThis study utilizes 16S rDNA gene sequencing technology and LC-MS/MS technology to examine the gut microbiota composition and serum metabolites of AML (acute myeloid leukemia) patients pre- and post-chemotherapy, in comparison to a control group of healthy individuals. Through screening, distinct microbiota and metabolites were identified in AML patients.Through the implementation of correlation analysis, a regulatory network linking gut microbiota and body metabolism in patients with AML was established, elucidating the pathophysiological mechanisms through which gut microbiota contribute to the metabolism of individuals with AML. These findings offer novel empirical evidence to support the implementation of gut microbiota-based intervention strategies for individuals diagnosed with AML. MethodsFecal and serum samples were obtained from 46 newly diagnosed acute myeloid leukemia (AML) patients at two distinct time points: prior to chemotherapy initiation and during the granulocytopenia phase following chemotherapy (neutrophil count <0.5×10^9/L), in addition to samples from 20 healthy adult controls. Subsequent analyses involved 16S rDNA sequencing and liquid chromatography-tandem mass spectrometry (LC-MS/MS). Differential microbiota and metabolites were identified using multivariate statistical methods, with functional annotation of the identified metabolites carried out using the Kyoto Encyclopedia of Genes and Genomes (KEGG) database.Moreover, Pearson correlation analysis was utilized to examine the co-metabolic patterns between the host and gut microbiota, with a specific emphasis on identifying the gut microbiota and metabolites that have a significant impact on the pathophysiological processes in patients with acute myeloid leukemia (AML) and investigating their interactions. Results 1. Based on multivariate statistical analysis, the alpha and beta diversity of the intestinal microbiota in AML patients was significantly reduced compared with the healthy control group, and remission-induction chemotherapy further reduced the abundance and diversity of the intestinal microbiota in AML patients.LC-MSmetabolomics analysis of all serum samples identified 430 differentially expressed metabolites between newly diagnosed AML patients and healthy controls, and 226 differentially expressed metabolites between AML patients in the neutropenic stage after induction chemotherapy and the newly diagnosed AML group.KEGG functional enrichment analysis of differential metabolites showed that significantly altered pathways in newly diagnosed AML patients included amino acid metabolism pathways such as valine, leucine, and isoleucine degradation, arginine and proline metabolism, phenylalanine metabolism, and histidine metabolism. Functional enrichment analysis in patients with neutropenic AML revealed significantly altered pathways such as bile secretion and bile acid metabolism, pyrimidine-glutathione metabolism, fatty acid biosynthesis, propionate metabolism, and the PI3K-Akt signaling pathway.Pearson correlation analysis revealed that AML patients possessed a unique interaction network between gut microbiota and serum metabolites. ConclusionThis study used 16S rDNA high-throughput sequencing and LC-MS/MS to analyze the gut microbiota and metabolites of healthy controls and newly diagnosed AML patients before and after chemotherapy. We found significant differences in gut microbial composition and metabolites between newly diagnosed AML patients and healthy controls. Remission-induction chemotherapy further reduced gut microbial diversity in newly diagnosed AML patients, exacerbating metabolic disorders. In addition, the differential metabolites and differential microbiota between the groups were correlated based on the Pearson correlation coefficient, indicating that AML patients have a unique intestinal microbiota and metabolite regulatory network. The correlation between related metabolic pathways and intestinal microbiota was analyzed, providing a basis for revealing the pathogenesis of AML and providing a new perspective for clinical auxiliary disease diagnosis, treatment and prognosis.

Objective This study was designed to evaluate the efficacy and safety of the azacitidine-venetoclax-G-CSF (VAG) combination regimen compared with a control regimen of idarubicin-cytarabine in newly diagnosed patients with acute myeloid leukemia (AML). Methods This is a retrospective study of VAG Regimen in newly diagnosed AML (ND-AML) patients. 40 ND-AML patients were treated at the Second People's Hospital of Huai'an and Siyang County Traditional Chinese Medicine Hospital, China, from January 2022 to September 2023. 24 patients received the VAG regimen, which consists of: Azacitidine subcutaneously at 75 mg/m2 on days 1-7, Venetoclax started at 100 mg on day 1, 200 mg on day 2, and 400 mg on days 3-28, G-CSF administered intravenously starting on day 1 when the peripheral blood white blood cell count was less than 4 × 10^9/L, with the goal of maintaining the white blood cell count below 25 × 10^9/L. For comparison, 16 ND-AML patients treated with the standard IA induction regimen at the same institution between October 2019 and April 2023 were included. The IA regimen consisted of: Idarubicin 10 mg/m2/day on days 1-3, Cytarabine 100 mg/m2/day on days 1-7. The primary end points were overall response rate (ORR) and complete response (CR) and CR with incomplete recovery (CRi). Results 1.Patient Characteristics and Response Rates A total of 40 ND-AML patients were enrolled in this study. 24 patients were treated with the VAG regimen, with a median age of 63 years (range: 18–83), 16 patients received the IA chemotherapy regimen, with a median age of 48 years (range: 19–64). Comparative efficacy analysis between the VAG and IA groups revealed the following: ORR: 100% (24/24) in the VAG group vs. 93.7% (15/16) in the IA group. CR/CRi rate: 88% (21/24) in the VAG group vs. 62.5% (10/16) in the IA group. MRD Negativity in CR/CRi Patients: 95.2% (20/21) in the VAG group vs. 50% (5/10) in the IA group. 2.Subgroup analysis by age demonstrated: Elderly Patients (≥60 years): CR/CRi rate of 85.7% (12/14) in the VAG group vs. 75% (3/4) in the IA group. Younger Patients (18–60 years): CR/CRi rate of 90.0% (9/10) in the VAG group vs. 58.3% (7/12) in the IA group.ELN Risk Stratification and Subtype Analysis VAG Group: Low-risk: CR/CRi rate of 100% (5/5). Intermediate-risk: CR/CRi rate of 88.9% (8/9). High-risk: CR/CRi rate of 80.0% (8/10). M5 Subtype: CR/CRi rate of 75% (3/4), compared to 90.0% (18/20) for other subtypes. IA Group: Low-risk: CR/CRi rate of 62.5% (5/8). Intermediate-risk: CR/CRi rate of 75% (3/4). High-risk: CR/CRi rate of 50% (2/4). M5 Subtype: CR/CRi rate of 33.3% (2/6), compared to 80% (8/10) for other subtypes.Genetic Subgroup Analysis VAG Cohort: DNMT3A, STAG2, and NPM1 mutations: Achieved a 100% CR/CRi rate (6/6, 4/4, and 4/4). FLT3-ITD mutation: CR/CRi rate of 100% (2/2). CEBPA and TET2 mutations: CR/CRi rate of 75% (3/4 each). SRSF2 mutation: CR/CRi rate of 60% (5/7). ASXL1, BCOR, and RUNX1 mutations: CR/CRi rate of 50% (2/4, 1/2, and 1/2). NRAS mutation: CR/CRi rate of 40% (2/5). IA Cohort: CEBPA and KRAS mutations: CR/CRi rate of 100% (4/4 and 2/2). FLT3-ITD mutation: CR/CRi rate of 83.3% (5/6). ASXL1, KIT, TET2, and DNMT3A mutations: CR/CRi rate of 50% (1/2 each). NRAS mutation: CR/CRi rate of 33.3% (1/3). 5.Treatment-Related Adverse Events and Supportive Care VAG vs.IA Group: Median duration of neutropenia: 7.83 days vs.16.88 days. Median duration of thrombocytopenia (<20 × 10⁹/L): 4.54 days vs.15.06 days. Mean red blood cell transfusions: 6.68 units vs.12.72 units. Mean platelet transfusions: 3.92 units vs.6.41 units. The most common grade 3 or higher adverse events in the VAG group included neutropenia (38%), febrile neutropenia (23%), thrombocytopenia (38%), and anemia (38%). Gastrointestinal symptoms were reported as the primary non-hematologic adverse events, all of which were manageable and classified as grade 1-2. No treatment-related deaths were reported in either group. Conclusions In ND-AML patients, no matter whether they were elder or younger patients, the VAG regimen demonstrated a higher response rate compared to the IA regimen. This suggests that the VAG regimen offers a promising treatment option for both young and elderly patients with ND-AML. Key words Acute myeloid leukemia; Venetoclax; Azacitidine；Granulocyte-Colony Stimulating Factor；

Acute myeloid leukemia (AML) is a highly aggressive hematological malignancy with a significant unmet clinical need for new therapeutic agents. Lysine-specific demethylase 1 (LSD1), a key regulator of leukemia stem cell self-renewal, has emerged as a promising epigenetic target for AML treatment. Herein, we employed an innovative multi-step integrated screening protocol, encompassing pharmacophore modeling, docking screening, molecular dynamics simulation, and biological evaluation, to identify novel LSD1 inhibitors. This comprehensive approach led to the discovery of six potent LSD1 inhibitors (we named these inhibitors LTMs 1–6), with LTM-1 exhibiting the most pronounced inhibitory effects on LSD1 (IC50 = 2.11 ± 0.14 nM) and the highest selectivity for LSD1 over LSD2 (>2370-fold). Notably, LTM-1 demonstrated outstanding antitumor activity both in vitro and in vivo. In vitro, LTM-1 showed potent anti-proliferative effects against LSD1-addicted MV-4-11 leukemia cells (IC50 = 0.16 ± 0.01 μM). In vivo, LTM-1 treatment significantly reduced tumor growth in MV-4-11 xenografted mice. Moreover, LTM-1 did not induce significant changes in liver and kidney function indices, suggesting a favorable safety profile. These results indicate that LTM-1 is a highly promising preclinical candidate for AML treatment, offering a new strategy for the development of more effective and selective LSD1 inhibitors.

Multiple myeloma, a hematological malignancy, shows PLK1 overexpression in cells correlates with poor prognosis, suggesting PLK1 as a potential therapeutic target. In this study, we discovered five peptides (PLs 1-5) targeting the polo box domain (PBD) of PLK1 through an integrated virtual screening strategy. MST assays confirmed that PLs 1-5 had strong binding affinity for PLK1, especially PL-1 (Kd = 3.11 ± 0.05 nM). Meanwhile, the kinase selectivity assay showed that the PL-1 had no significant inhibitory effects on a panel of other kinases. Molecular dynamics simulation further demonstrated the structural stability of PL-1 and PLK1 complex. Notably, PL-1 displayed potent antiproliferative efficacy against U266 multiple myeloma cells (IC50 = 0.09 ± 0.01 µM). PL-1 showed high intracellular uptake capacity. In addition, PL-1 exhibited good biostability in human serum and liver microsomes. Taken together, PL-1 is a potent and highly selective antitumor agent with considerable therapeutic promise for multiple myeloma.

ObjectiveThe aim of this study was to identify dual-target inhibitors of FMS-like tyrosine kinase 3 (FLT3) and histone deacetylase 8 (HDAC8) using structure-based virtual screening technology, and to systematically investigate their mechanisms of action in the context of anti-acute myeloid leukemia (AML) therapy. MethodsVirtual Screening and Molecular Docking:The crystal structures of FLT3 (PDB ID: 6IL3) and HDAC8 (PDB ID: 1T69) were obtained from the Protein Data Bank (PDB) and the conformation was optimized for energy minimization by Molecular Operating Environment (MOE) software.After screening candidate molecules from an internal database of 35,000 compounds and converting their two-dimensional structure into three-dimensional conformation, MOE's Dock tool was used to attach the target protein active site, and the binding affinity was evaluated by dG scoring algorithm.In Vitro Inhibition Assays:A standardized kinase response and HDAC8 fluorescence assay kit (Fluor de Lys®-HDAC8) was used to determine the compound's half-inhibitory concentration (IC50) for FLT3 and HDAC8.Molecular Dynamics (MD) Simulations：GROMACS software (version 2021.5) and AMBER99SB-ILDN force field were used to simulate FH-5 and the target protein complex for 50 ns, and root mean square deviation (RMSD), root mean square fluctuation (RMSF) and secondary structure stability were analyzed.In Vitro Antiproliferation Assay：MTT assay was used to evaluate the inhibitory activity of FH-5 on the proliferation of KG-1 leukemia cells.In Vivo Antitumor Testing：A xenograft model of KG-1 cells (nu/nu mice) was established, and FH-5 (2.5, 5, 10 mg/kg) was administered in groups to monitor the changes in tumor volume and body weight, and the dose-dependent effects were analyzed. Results1. Six potential dual-target inhibitors (FHs 1-6) were virtually screened out, and the docking scores of FH-5 against FLT3 and HDAC8 were significantly better than those of the positive controls quinzatinib (−12.61 kcal/mol) and volinota (−12.65 kcal/mol). 2. In vitro enzyme inhibition experiments showed that the IC50 value of FH-5 against FLT3 and HDAC8 was 0.31 ± 0.02 nM and 2.91 ± 0.79 nM, respectively, and the activity was 32 times that of quinzatinib and 3 times that of vorinoat. 3. Molecular dynamics simulation showed that the main chain RMSD of FH-5 and FLT3 and HDAC8 complexes stabilized below 0.7-0.9 nm and 0.2 nm, respectively, and the fluctuation value of key residues (such as Arg834 of FLT3 and Asn178 of HDAC8) was lower than 0.4 nm, which verified the binding stability. 4. The proliferation inhibition rate of FH-5 on KG-1 cells exceeded 95%, and the IC50 value was 23.2 nM. 5. In vivo experiments, the tumor inhibition rate of 10 mg/kg FH-5 group reached 78%, and the weight of mice was not significantly affected, showing a dose-dependent anti-tumor effect (P< 0.001). ConclusionIn this study, we successfully obtained the FLT3/HDAC8 dual-target inhibitor FH-5 through structure-based virtual screening technology. It stably binds to the active site of the target protein through hydrogen bonding, hydrophobic interaction and ionic bonding, and shows strong anti-AML activity in vitro and in vivo, providing a novel candidate drug and theoretical basis for the treatment of AML. Key words Fms-like tyrosine kinase 3; histone deacetylase 8; acute myeloid leukemia; dual-targeting inhibitors; structure-based virtual screening

OBJECTIVES:Relapsed/refractory acute B-cell lymphoblastic leukemia (R/R B-ALL) often responds poorly to induction chemotherapy. However, recent research has shown a novel and effective drug treatment for R/R B-ALL.METHODS:A total of eight patients with R/R B-ALL were enrolled in the study from November 2021 to August 2022. All patients received chemotherapy based on a combination regimen of venetoclax and azacitidine. The regimen was as follows venetoclax 100 mg d1, 200 mg d2, 400 mg d3-14, azacitidine 75 mg/m2 d1-7.RESULTS:Five of eight patients achieved very deep and complete remission (CR) with minimal residual disease (MRD) less than 0.1%. One patient achieved partial remission. Two patients did not achieve remission. There were no serious adverse events and all patients were well tolerated. Three patients were eligible for consolidation chemotherapy and were bridged to CAR-T therapy.CONCLUSIONS:The combined regimen of venetoclax and azacitidine may be beneficial for patients with R/R B-ALL.

通过总结恶性淋巴瘤(ML)不同时期的症结及变化规律,探讨ML最根本的中医病机,也就是中医治疗可能的"靶标".ML初始成因乃寒、痰搏结而后生瘀,其发生发展规律乃太阳中风,寒客于卫,邪盛卫虚,开阖失度,肺失宣肃,不司水道,津停液凝,结于经隧,与毒相合.病机要素涉及寒、痰、毒、瘀,且互有兼夹.临证紧扣卫气亏虚,不能御邪,气化失司,液凝生痰为主,治宜行卫气,通津液以求阴阳平衡,治愈顽疾.

OBJECTIVE:To investigate the efficacy and safety of venetoclax (VEN) combined with demethylating agents (HMA) in the treatment of relapsed/refractory acute myeloid leukemia (R/R AML).METHODS:The clinical data of 26 adult R/R AML patients who received the combination of VEN with azacitidine (AZA) or decitabine (DAC) in Huai'an Second People's Hospital from February 2019 to November 2021 were retrospectively analyzed. The treatment response, adverse events as well as survival were observed, and the factors of influencing the efficacy and survival were explored.RESULTS:The overall response rate (ORR) of 26 patients was 57.7% (15 cases), including 13 cases of complete response (CR) and CR with incomplete count recovery (CRi) and 2 cases of partial response (PR). Among the 13 patients who got CR/CRi, 7 cases achieved CRm (minimal residual disease negative CR) and 6 cases did not, with statistically significant differences in overall survival (OS) and event-free survival (EFS) between the two groups (P=0.044, 0.036). The median OS of all the patients was 6.6 (0.5-15.6) months, and median EFS was 3.4 (0.5-9.9) months. There were 13 patients in the relapse group and refractory group, respectively, with response rate of 84.6% and 30.8% (P=0.015). The survival analysis showed that the relapse group had a better OS than the refractory group (P=0.026), but there was no significant difference in EFS (P=0.069). Sixteen patients who treated for 1-2 cycles and 10 patients who treated for more than 3 cycles achieved response rates of 37.5% and 90.0%, respectively (P=0.014), and patients treated for more cycles had superior OS and EFS (both P<0.01). Adverse effects were mainly bone marrow suppression, complicated by various degrees of infection, bleeding, and gastrointestinal discomfort was common, but these could be all tolerated by patients.CONCLUSION:VEN combined with HMA is an effective salvage therapy for patients with R/R AML and is well tolerated by patients. Achieving minimal residual disease negativity is able to improve long-term survival of patients.

目的:探究阿扎胞苷(Azacitidine,AZA)单药或联合HAG方案治疗骨髓增生异常综合征(Myelodysplastic syndromes,MDS)的临床疗效及安全性.方法:回顾性分析49例MDS患者的临床资料,根据治疗方法不同分为支持治疗组和含AZA组(单药或联合HAG方案),统计分析患者的临床疗效及不良反应情况.结果:支持治疗组的总有效率(Overall response rate,ORR)为30.00％(6/20),包括0例完全缓解(Complete remission,CR),1 例骨髓完全缓解(Marrow complete remission,mCR),2例部分缓解(Partial remission,PR),3例血液学改善(Hematological improvement,HI).含 AZA 组的ORR 为65.52％,包括8例 CR、2例 mCR、4例PR、5例HI.其中单药组的ORR为46.67％,包括2例CR、1例mCR、2例PR、2例HI;联合组的ORR为85.71％,包括6例CR、1例mCR、2例PR、3例HI.与支持治疗组相比,含AZA组的完全缓解率(CR+mCR)及ORR显著增高,差异有统计学意义(P＜0.05).患者最常见的不良反应是Ⅲ-Ⅳ级骨髓抑制(18/29)及继发感染(10/29),且随着疗程数的增加不良事件逐渐减少.含AZA组患者的中位总生存(Overall survival,OS)时间及中位无进展生存时间(Progression-free survival,PFS)时间显著延长(P＜0.05).结论:该小系列研究的初步结果表明,与支持治疗相比,AZA单药或联合HAG方案治疗MDS有更高的治疗反应,可延长患者总生存期,患者有良好的耐受性,且联合治疗方案可能有更好的疗效.

OBJECTIVE To evaluate the incidence and clinical characteristics of metabolic syndrome (MS) within one year after hematopoietic stem cell transplantation (HSCT) in order to screen the risk factors for HSCT-MS, provide early intervention and improve the long-term quality of survival of patients. METHODS The clinical follow-up data of 64 HSCT patients (survival time > 1 year) who received HSCT in our center from January 2007 to August 2018 were collected. Among them, 50 cases were allogeneic hematopoietic stem cell transplantation (allo-HSCT) and 14 cases were autologous hematopoietic stem cell transplantation (auto-HSCT). The changes of MS-related indexes and clinical characteristics before and 1, 3, 6 and 12 months after HSCT were analyzed retrospectively. RESULTS In allo-HSCT group, 14 cases were diagnosed as MS before operation, including high-density lipoprotein cholesterol (hypo-HDL-C)> hyper triglycerides（hyper-TG）> hyper fasting glucose（hyper-FBG）> abdominal obesity (AO) > hypertension. The preoperative diagnosis of MS in the auto-HSCT group was 5 cases, in the order of hyper-FBG> hyper-TG> AO> hypo-HDL-C> hypertension. Incidence of MS at 1, 3, 6 and 12 months after transplantation: 19, 26, 24 and 20 cases in the allo-HSCT group, respectively; auto-HSCT group were 7, 7, 6 and 6 cases, respectively. Hyper-TG and hypo-HDL-C were prominent in both groups. CONCLUSION The incidence of HSCT-MS is significantly higher within 1 year after HSCT. Regardless of allo-HSCT and auto-HSCT, the prevention and control of HSCT-MS is emphasized as an important guarantee to improve the long-term survival quality of HSCT patients.

Background. Hematopoietic stem cell transplantation (HSCT) is potentially curative for severe aplastic anemia (SAA). Graft failure (GF) remains a life-threatening complication after HSCT. Preexisting anti-HLA antibodies, especially HLA-specific antibodies (DSA), have been demonstrated as a risk of GF. Case presentation. This report describes a woman with acquired SAA who presented with anti-HLA antibodies and GF. After the treatment of anti-HLA antibodies, engraftment was achieved through a second alternative donor HSCT. This work complied with the Declaration of Helsinki and the Declaration of Istanbul. Conclusions. Based on our experience in treating this case, we hold that the presence of preoperative anti-HLA antibodies could discount the efficacy of HSCT and anti-HLA antibody screening should be performed before HSCT. Additionally, a second HSCT is feasible to prolong survival.

Objectives To compare the outcomes of antihuman T lymphocyte globulin (ATG-F) and porcine antihuman lymphocyte globulin (p-ALG) as part of a conditioning regimen in hematopoietic stem cell transplantation (HSCT) for severe aplastic anemia (SAA). Methods we performed a retrospective analysis, evaluating the outcome of patients with SAA who received ATG-F based conditioning (n = 26) with those receiving p-ALG conditioning (n = 34). Results The median time to neutrophil engraftment was 11 days (range, 8 - 38) and 11 days (range, 9 - 24) in the p-ALG and ATG-F groups (P = 0.857); the median platelet engraftment time was 15 (range, 9 - 330) days and 13 (range, 10 - 56) days (P = 0.155). There were no significant differences in grades II - IV acute graft-versus-host disease (aGVHD), grades III - IV aGVHD, chronic GVHD (cGVHD), and the moderate-severe cGVHD between the ATG-F and p-ALG groups (P>0.05). Discussion Patients in the ATG-F group functioned significantly better on role-physical (P = 0.006), general health (P = 0.029), and physical component summary (P = 0.009). The estimated overall survival and failure free survival rates at 5 years were 88.5% +/- 6.3% vs. 82.4% +/- 6.5% (P = 0.515), 84.6% +/- 7.1% vs. 79.4% +/- 6.9%, respectively (P = 0.579). The infection rates were 61.53% and 47.05%, respectively (P = 0.265). Conclusion As part of the conditioning regimen, p-ALG achieved a similar efficacy as ATG-F without increasing the incidence of transplantation complications in SAA patients.

Purpose: To identify the biological function of phosphoserine aminotransferase 1 (PSAT1) in regulating cell proliferation and apoptosis in multiple myeloma (MM).Methods: The mRNA and protein levels of PSAT1 were determined using quantitative real-time polymerase chain reaction (PCR) and western blotting, respectively. Cell proliferation was measured using CCK-8 assay.Results: PSAT1 mRNA and protein expression levels were significantly increased in MM cell lines when compared to control cells. Moreover, downregulation of PSAT1 inhibited MM cell proliferation and induced cell apoptosis, whereas overexpression of PSAT1 promoted MM cell proliferation and suppressed cell apoptosis. Further analysis demonstrated that the underlying mechanism was via regulation of PI3K/AKT pathway.Conclusion: The results identified a novel role for PSAT1 in the progression of MM, which may provide a therapeutic and a new anticancer target for the therapy of MM. Keywords: Multiple myeloma, PSAT1, Cell proliferation, PI3K/AKT pathway

PURPOSE:To compare the efficacy and impact of GEMOX and GDP in the treatment of patients with non-Hodgkin's lymphoma (NHL).METHODS:A total of 68 patients with NHL admitted to the hospitals of the authors from February 2013 to April 2016 were equally distributed into the GEMOX Group (treated with Gemcitabine and Oxaliplatin) and the GDP Group (treated with Gemcitabine, Cisplatin, and Dexamethasone), with cycle repetition every 3 weeks. The efficacy was analyzed every two weeks. The side effects were analyzed once a week. Comparison of survival was performed using Kaplan-Meier method and log-rank test and Cox univariate and multivariate regression analyses.RESULTS:Efficacy in the two groups was not statistically different (p>0.05). The incidence of III-IV grade of nausea and vomiting in the GDP Group was higher than in the GEMOX Group (p<0.05). The overall incidence decreased hemoglobin, nausea and vomiting, and renal dysfunction of the GDP Group was also higher than in the GEMOX Group (p<0.05). Analysis by multivariate Cox model found that the clinical classification and the grade of malignancy were independent prognostic factors (p<0.05). The odds ratio (OR) values of the clinical classification in the GEMOX Group and the GDP Group were 2.874 and 24.074, respectively. The OR values of the grade of malignancy in the GEMOX Group and the GDP Group were 14.034 and 6.873, respectively.CONCLUSION:Both the GEMOX regimen and the GDP regimen had good short-term efficacy on NHL patients, but the GEMOX regimen is to be preferred since as it had fewer side effects than the GDP regimen.

Objective:To investigate the relationship between mitogen-activated protein kinase (MAPK) signaling pathway related signal molecules and the apoptosis of acute promyelocytic leukemia NB4 cells induced by puerariae radix flavones (PRF) and its significance.Methods:The cells were divided into control group [0.025% dimethyl sulfoxide (DMSO) to replace PRF] and 10, 30, 50 μg/ml PRF groups. The proliferation inhibition rate of NB4 cells exposed with PRF for 24, 48 and 72 hours was determined by methyl thiazolyl tetrazolium (MTT) method, and the nuclear morphology was determined by confocal laser scanning microscope after 48 hours. NB4 cells were divided into control group (adding 0.025% DMSO) and 10, 30 and 50 μg/ml PRF with or without 10 μmol/L c-Jun N-terminal kinase (JNK) inhibitor (SP600125) group, and the cells were treated for 48 hours and the changes in the expressions of MAPK pathway related proteins JNK, tumor necrosis factor α (TNF-α), extracellular signal-regulated kinase (ERK) and p38 MAPK were tested by Western blot.Results:10, 30 and 50 μg/ml PRF inhibited the proliferation of NB4 cells in 24, 48 and 72 hours, which was in time- and dose-dependent manners (all P < 0.05). The half-maximal inhibitory concentration (IC 50) at 24, 48 and 72 hours were (40.03±2.23) μg/ml, (22.92±1.72) μg/ml and (17.99±1.48) μg/ml, respectively. The confocal laser scanning microscope showed that NB4 cells displayed distinct apoptotic characteristics after PRF treatment. After co-cultivating NB4 cells with 10 μmol/L SP600125 and different concentrations of PRF for 48 hours, the expression of JNK1 in NB4 cells was suppressed ( P < 0.05), and the expressions of JNK2/3 and p38 MAPK decreased, but the differences were not statistically significant (both P > 0.05). The expressions of ERK1 and ERK2 gradually increased in the single-drug group, while the expression in the combined drug group decreased. The expression of TNF-α in the 50 μg/ml PRF+SP600125 group was down-regulated compared with the 50 μg/ml PRF single-drug group, while the expressions in the 10 and 30 μg/ml PRF+SP600125 groups were up-regulated compared with the 10 and 30 μg/ml PRF single-drug groups. Conclusion:10-50 μg/ml PRF may activate the MAPK signaling pathway through TNF-α. JNK, ERK1/2 and p38 MAPK interact with each other to activate pro-apoptotic related proteins and induce NB4 cells apoptosis.

BackgroundThe incidence of acute myeloid leukemia (AML) increases with age. The overall prognosis remains poor for older patients. Studies on the efficacy of decitabine, an epigenetic agent, in older patients with AML have reported conflicting results.Materials and MethodsFor this meta-analysis, we performed a literature search and collected 38 studies (including 3298 patients with AML) to evaluate the role of decitabine in elderly patients with AML. We used complete response (CR) or overall response (OR) rate as indicators of effectiveness.ResultsPatients treated with decitabine have a higher CR/OR rate than those treated with low-dose cytarabine (CR, 2.60; 95% confidence interval [CI], 1.64-4.14; OR, 4.88; 95% CI, 1.98-12.04) or CAG/HAG (low-dose epirubicin and cytarabine with granulocyte stimulating factor/low-dose homoharringtonine and cytarabine with granulocyte stimulating factor) regimens (CR, 2.53; 95% CI, 1.98-3.23; OR, 2.89; 95% CI, 2.24-3.73). However, patients treated with decitabine had a CR rate equivalent to those treated with intensive chemotherapy (CR, 0.58; 95% CI, 0.28-1.22; P = .15). Use of decitabine in combination with other regimens resulted in a higher CR/OR rate than did use of decitabine alone (P < .001); there was no significant difference in infection rates and early death rates (P > .05).ConclusionThe findings presented in this article show that decitabine is effective and safe for the treatment of older patients with AML.

Objective To investigate the correlation between the miR-125b expression and subtypes of acute myeloid leukemia (AML).Methods Sixty-seven AML patients were enrolled in the observation group at Huai'an Hospital Affiliated to Xuzhou Medical College between January 2015 and December 2015.Thirty patients with non-malignant hematologic diseases were selected as the control group in the same period.The expression levels of miR-125b in bone marrow ceils were detected by quantitative polymerase chain reaction (PCR) in both groups.The expression levels of miR-t25b in different subtypes were compared with the control group and the correlation between expression of miR-125b and chemotherapy efficacy was analyzed.Results The expression levels of miR-125b were 2.1 ±0.4,2.2 ±0.4,3.4 ± 1.0,1.9 ± 0.4,1.9 ±0.3 and 1.8 ±0.4,respectively in patients with M1 ～ M6 for the observation group and the expression level of miR-125b was 0.8 ±0.2 for the control group.The expression levels of miR-125b were significantly higher in all AML subtypes in the observation group than the control group (all P ＜ 0.05) with the expression level of miR-125b significantly higher in patients with AML M3 than in patients with other subtypes (P ＜0.05).For the observation group,the expression level of miR-125b was 2.9 ±0.4,1.6 ±0.2 and 2.5 ± 0.3,respectively in patients before the treatment,and in patients with and without remission after the treatment.The expression level of miR-125b was 0.8 ±0.2 for the control group.Compared with before the treatment,the level of miR-125b significantly decreased in patients with remission were but still significantly higher than the control group (P ＜ 0.05).Conclusion miR-125 b is overexpressed in AML patients and the level of miR-125b significantly decreased compared with before the chemotherapy.The expression level of miR-125b may be related to the development of AML.

The chromosomal translocation t(14;18)(q32;q21) is commonly associated with neoplasms of follicular center cell origin and has also been reported in cases of chronic lymphocytic leukemia. However, T cell acute lymphoblastic (or lymphocytic) leukemia (T-ALL) with t(14;18)(q32;q21) has been rarely reported. Here, we report a case of myeloid antigen-positive T-ALL (My+T-ALL) with t(14;18)(q32;q21) and trisomy 10. This is the first reported case of My+T-ALL (L2) with such chromosomal abnormalities. Other published de novo ALL cases, with t(14;18)(q32;q21) and without a documented history of lymphoma, are summarized and reviewed in this report. The patient in this study was treated with remission induction therapy and intensive chemotherapy, followed by maintenance therapy. As of this writing, he has remained in remission for more than 3 years and has presented a better clinical outcome compared with other reported adult ALL patients with t(14;18)(q32;q21).