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Chronic myelomonocytic leukemia (CMML) is a clonal hematopoietic stem cell malignancy and the only curable therapy is allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, allo-HSCT is not appropriate for all CMML patients, and relapse is the leading cause of treatment failure. This project conducted a nationwide multicenter real-world study to develop a novel prediction scoring system for early relapse. A total of 238 CMML patients from twenty-seven medical centers treated with allo-HSCT, and 307 adult patients with CMML who underwent allo-HSCT in a publicly available research dataset from the Center for International Blood and Marrow Transplantation Registry (CIBMTR) database were included. Independent prognostic factors for the early relapse of CMML posttransplantation were identified according to competing risk regression methods. Four prognostic factors were identified: bone marrow blasts >10% (hazard ratio [HR], 4.262; P = 0.014), age >60 years (HR, 6.221; P = 0.007), hemoglobin level <100 g/L (HR, 3.695; P = 0.004), and non TET2 gene mutation (HR, 3.425; P = 0.017). A risk-grading scoring system was developed based on the regression coefficients and patients were stratified into low-risk (0-1 point), intermediate-risk (1.5-2 points) and high-risk ( > 2 points) groups. The validated internal c-statistic was 0.767 (95% confidence interval [CI], 0.674-0.860), and the external c-statistic was 0.769 (95% CI, 0.703-0.836). In the derivation cohort, the cumulative incidence rates of early relapse in the low-risk, intermediate-risk, and high-risk groups were 1.35% (95% CI: 1-4%), 10.40% (95% CI: 4-16%), and 29.54% (95% CI: 16-39%) (P < 0.001), respectively. This scoring system can be utilized to early identification of patients at a high risk of relapse and contributing to the implementation of urgent medical support., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Membranous nephropathy (MN) is a rare complication that can occur after allogeneic hematopoietic stem cell transplantation (allo-HSCT). MN patients may develop nephrotic syndrome or even kidney failure, which greatly affects their quality of life and prognosis. However, current knowledge regarding MN after allo-HSCT is limited. Thus, a multicenter nested case‒control study was conducted. Patients who had been diagnosed with MN after allo-HSCT were retrospectively identified at 8 HSCT centers. A total of 51 patients with MN after allo-HSCT were included. The median age of MN patients after allo-HSCT was 38 years, and the median duration from HSCT to MN was 18 months. The use of HLA-matched donors (P = 0.0102) and peripheral blood as the graft source (P = 0.0060) were identified as independent predisposing risk factors for the onset of MN after allo-HSCT. Compared to those in the control group, the incidence of extensive chronic graft-versus-host disease was greater in the MN patients (P = 0.0002). A total of 31 patients developed nephrotic syndrome. Patients receiving combination treatments of corticosteroids and immunosuppressants appeared to have better outcomes. In conclusion, MN is a rare but occasionally severe complication following HSCT and may require active treatment., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

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., (© 2023 Wiley Periodicals LLC.)

Objective: To investigate the risk factors of oral ulcers and bloodstream infection in patients with hematopoietic stem cell transplantation., Methods: The clinical data of 401 hematopoietic stem cell transplant patients in the First Affiliated Hospital of Zhengzhou University from January 2020 to December 2021 were retrospective analyzed, and the risk factors of oral ulcers and bloodstream infection statistical and analyzed., Results: Among the 401 patients, the incidence of oral ulcers was 61.3% (246/401), and the incidence of bloodstream infection was 9.0% (36/401). A total of 40 strains of pathogenic bacteria were isolated from 36 patients, including 26 strains of Gram negative strains (65%), 13 strains of Gram positive strains (32.5%), and 1 strain of fungi (2.5%). Single-factor analysis showed that oral hygiene was associated with the occurrence of bloodstream infection, and the Multi-factor analysis showed that age ≥14 years old, disease diagnosis of leukemia, and allogeneic hematopoietic stem cell transplantation were risk factors for oral ulcers., Conclusion: The incidence of oral ulcers in patients with hematopoietic stem cell transplantation is high. The age ≥14 years, disease diagnosis of leukemia, and allogeneic hematopoietic stem cell transplantation were risk factors for oral ulcers in patients, and oral hygiene was associated with the occurrence of bloodstream infection.

To analyze the clinical characteristics, diagnosis, treatment and outcome of patients with thrombotic thrombocytopenic purpura (TTP). The clinical data of 69 adult patients with TTP were retrospectively analyzed. There were 19 males and 50 females with a median age of 42 (18-79) years. PLASMIC score 6-7 was recognized in 82.8% (53/64) patients. The activity of von Willebrand factor-cleaving protease (ADAMTS13), which was detected in 21 patients before treatment, was less than 5% in 17 patients and 5%-10% in 3 patients. All 69 patients were treated with plasma exchange (PEX) and/or fresh frozen plasma infusion (PI), 43 of whom were also given glucocorticoid. In addition to PEX/PI and glucocorticoid, rituximab and/or immunosuppressants were administrated in 20 patients. The median follow-up time was 12 (1-57) months. The remission rate was 69.6%, while the relapse rate was 11.6%. The 2-year overall survival (OS) rate was 69.6%±5.5%. The univariate and multivariate analysis showed that relapsed/refractory disease was an independent risk factor for OS. The 2-year OS rate of relapsed/refractory patients was significantly lower than that of the rest patients (41.5%±9.8% vs. 83.7%±5.6%, P <0.001). Regarding the unfavorable prognosis in relapsed/refractory patients, rituximab and/or immunosuppressants are strongly recommended for sake of improving the overall survival.

Steroid-refractory (SR) acute graft-versus-host disease (aGVHD) is one of the leading causes of early mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT). We investigated the efficacy, safety, prognostic factors, and optimal therapeutic protocol for SR-aGVHD patients treated with basiliximab in a real-world setting. Nine hundred and forty SR-aGVHD patients were recruited from 36 hospitals in China, and 3683 doses of basiliximab were administered. Basiliximab was used as monotherapy (n = 642) or in combination with other second-line treatments (n = 298). The cumulative incidence of overall response rate (ORR) at day 28 after basiliximab treatment was 79.4% (95% confidence interval [CI] 76.5%-82.3%). The probabilities of nonrelapse mortality and overall survival at 3 years after basiliximab treatment were 26.8% (95% CI 24.0%-29.6%) and 64.3% (95% CI 61.2%-67.4%), respectively. A 1:1 propensity score matching was performed to compare the efficacy and safety between the monotherapy and combined therapy groups. Combined therapy did not increase the ORR; conversely, it increased the infection rates compared with monotherapy. The multivariate analysis showed that combined therapy, grade III-IV aGVHD, and high-risk refined Minnesota aGVHD risk score before basiliximab treatment were independently associated with the therapeutic response. Hence, we created a prognostic scoring system that could predict the risk of having a decreased likelihood of response after basiliximab treatment. Machine learning was used to develop a protocol that maximized the efficacy of basiliximab while maintaining acceptable levels of infection risk. Thus, real-world data suggest that basiliximab is safe and effective for treating SR-aGVHD., (© 2022 Wiley Periodicals LLC.)

Objective: To analyze the characteristics of gene mutation and overexpression in newly diagnosed multiple myeloma (NDMM) patients., Methods: Bone marrow cells from 208 NDMM patients were collected and analyzed. The gene mutation of 28 genes and overexpression of 6 genes was detected by DNA sequencing. Chromosome structure abnormalities were detected by fluorescence in situ hybridization (FISH)., Results: Gene mutations were detected in 61 (29.33%) NDMM patients. Some mutations occurred in 5 or more cases, such as NRAS, PRDM1, FAM46C, MYC, CCND1, LTB, DIS3, KRAS, and CRBN. Overexpression of six genes (CCND1, CCND3, BCL-2, CCND2, FGFR3, and MYC) were detected in 83 (39.9%) patients, and cell cycle regulation gene was the most common. Single nucleotide polymorphisms (SNP) changes were detected in 169 (81.25%) patients, the TP53 P72R gene SNP (70.17%) was the most common. Abnormality in chromosome structure was correlated to gene overexpression. Compared to the patients with normal chromosome structure, patients with 14q32 deletion showed higher proportion of CCND1 overexpression. Similarly, patients with 13q14 deletion showed higher proportion of FGFR3 overexpression, whereas patients with 1q21 amplification showed higher proportion of CCND2, BCL-2 and FGFR3 overexpression., Conclusion: There are multiple gene mutations and overexpression in NDMM. However, there is no dominated single mutation or overexpression of genes. The most common gene mutations are those in the RAS/MAPK pathway and the genes of cyclin family CCND are overexpression.

Between 2008 and 2019, 58,914 hematopoietic stem cell transplantations (HSCTs) were reported to the Chinese Blood and Marrow Transplantation Registry Group (CBMTRG) throughout China. In this report, we focus on 2019 data and describe current trends in HSCT in China. There was continued growth in transplant activity in China, with a rapid increase in haploidentical HSCT. In 2019, a total of 12,323 cases of HSCT were reported from 149 transplant teams, 78% (9597 cases) were allogeneic HSCTs. Haploidentical donor (HID) HSCT accounted for 60% (5771 cases) of allogeneic HSCT. The most common indications for allogeneic HSCT for malignant disease were acute myeloid leukemia (AML) (37%) and acute lymphoblastic leukemia (ALL) (24%), and the largest proportion of non-malignant diseases comprised aplastic anemia (AA) (13%). Multiple stem cell source composed 70% of HID and 28% of MSD, which was typical in China. The BuCy based regimen (59%) was the most popular conditioning regimen for allogeneic HSCT, followed by the BuFlu based regimen (23%) and TBI-based regimen (12%). This survey clearly shows comprehensive information about the current state and recent trends for HSCT in China. Further efforts should be made to obtain detailed information., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

Objective: To analyze the clinical characteristics of patients with POEMS syndrome and explore its effective treatment strategies., Methods: The clinical data of 75 patients with POEMS syndrome treated in The First Affiliated Hospital of Zhengzhou University from June 2012 to June 2018 were collected and retrospectively analyzed. The clinical characteristics, treatment regimes and outcomes of the patients were summarized., Results: The median age of 75 diagnosed patients was 50 (30-81) years old and 100% (75/75) of the patients were accompanied with peripheral neuropathy, 77.3% (58/75) with organ enlargement, 82.7% (62/75) with endocrine abnormality, 93.3% (70/75) with monoclonal plasma cell diseases and 64.0% (48/75) with skin changes. Among the 75 patients, 5 cases gave up treatment, while the others showed varying degrees of improvement after treatment. The hematological complete remission (CR H ) rate of the 70 patients was 28.6% and the rate of neurological remission (R N ) was 85.7%. BD and RD regimens showed better efficacy in CR H and R N than old schemes, such as VAD and COP (P<0.05). Two patients underwent sequential autologous hematopoietic stem cell transplantation (HSCT) after BD chemotherapy and achieved ideal therapeutic effects, including the significant improvement of peripheral neurological symptoms and the M protein turned negative. The median follow-up time of the 70 patients was 42 (4-103) months, while the 2-year overall survival rate (OS) was 86.7%, and the 5-year OS was 81.0%., Conclusion: The clinical manifestations of POEMS syndrome are complex and diverse, the clinicians therefore should be vigilant to reduce the misdiagnosis and missed diagnosis. Bortezomib or Lenalidomide can be recommended as the first-line medicines and autologous HSCT should be considered for appropriate patients.

Objective: To investigate the expression and clinical significance of serum protein ROCK2 in patients with chronic graft-versus-host disease (cGVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT)., Methods: The patients were divided into cGVHD group and control group (without cGVHD). The expression levels of serum protein ROCK2 were detected by ELISA in patients with or without cGVHD after allo-HSCT., Results: The expression level of ROCK2 in serum of cGVHD patients was significantly higher than those in control group, moreover, the expression level of ROCK2 in severe cGVHD group was significant higher than that in moderate and mild cGVHD group (P<0.001). The expression level of ROCK2 was significantly decreased in the serum of cGVHD patients after treatment（P＜0.01）; the expression level of ROCK2 was significantly higher in the serum of cGVHD patients with lung as the target organ（P＜0.01）. The median survival time of patients with severe cGVHD were significantly shorter than that of patients with mild and moderate cGVHD（P＜0.05）., Conclusion: ROCK2 shows certain reference value in the evaluation of severity and prognosis of cGVHD, and may be a new target for the treatment of cGVHD.

Background: Post-transplant relapse remains a principal leading cause of failure after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with adult acute lymphoblastic leukemia (ALL). The aim of this study was to investigate the efficacy and safety of low-dose decitabine on the prevention of adult ALL relapse after allo-HSCT., Methods: In this prospective study, we enrolled 34 patients with ALL who underwent allo-HSCT from August 2016 to April 2020 and received low-dose decitabine maintenance treatment after transplantation. The primary objectives were cumulative incidence of relapse rate (CIR), overall survival (OS), and disease-free survival (DFS). The secondary objectives were graft- versus -host disease (GVHD) and safety., Results: Among the enrolled 34 patients, 6 patients relapsed and 6 patients died. The 2-year CIR, OS, and DFS were 20.2, 77.5, and 73.6%, respectively. Subgroup analysis revealed the 2-year CIR, OS, and DFS rates of 12 patients with T-ALL/lymphoblastic lymphoma (LBL) were 8.3, 90, and 81.5%, respectively. None of the seven patients with T-ALL relapsed. During maintenance treatment, only one patient (2.9%) developed grade IV acute GVHD and four (11.8%) patients had severe chronic GVHD. Thirty-two patients (94.1%) developed only grade I to II myelosuppression, and two patients (5.8%) developed grade III to IV granulocytopenia., Conclusions: Maintenance treatment with low-dose decitabine after allo-HSCT may be used as a therapeutic option to reduce relapse in patients with adult ALL, especially in patients with T-ALL. Our findings require confirmation in larger-scale controlled trials., Clinical Trial Registration: Chinese Clinical Trials Registry, identifier ChiCTR1800014888., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Liu, Jiang, Xie, Wan, Cao, Wang, Liu, Dong, Wang, Lu, Zhang, Cheng, Fan, Li, He and Guo.)

Objective: To investigate the prognostic significance of different IDH mutations and accompanying gene mutations in patients with non-M(3) acute myeloid leukemia (AML) . Methods: Second-generation sequencing was performed to detect the mutations of 22 genes in 389 patients with AML in the First Affiliated Hospital of Zhengzhou University from June 2016 to December 2018, and Kaplan-Meier and Cox regression models were used to analyze the prognostic factors. Results: The mutation frequency of IDH1 and IDH2 was 6.2% and 8.7% , respectively, in all patients without co-mutation. The IDH2 mutant group had an older age, higher proportion of bone marrow primitive cells, more common normal karyotype, and more common RUNX1 and SRSF2 mutations compared with IDH2 wild-type group. Univariate analysis of variance showed that the median OS and PFS of IDH1 mutation group were significantly shorter than those of the wild-type group ( P <0.05) . IDH2 mutation as a single variable and IDH2R140 mutation had no significant effect on the prognosis, while different mutation sites had different effects. Compared with the IDH2 wild-type group, the IDH2R172 mutation group had lower complete remission (CR) rate and shorter median OS and PFS ( P <0.05) . In patients with normal karyotypes or aged ≥50 years, IDH2 mutation as a single variable had no significant effect on the prognosis, IDH1 mutation and IDH2R172 mutation were associated with poor OS and PFS ( P <0.05) , and IDH2R140 mutation had no significant effect on OS and PFS. Approximately 74.1% (43/58) of patients with IDH mutation simultaneously carried other gene mutations; however, the number of accompanying gene mutations had no significant effect on the prognosis. Among 58 patients with IDH mutation, the CR rate of patients with NPM1 mutation was significantly higher than that of patients in the NPM1 wild-type group (81.8% vs 36.4% , P =0.014) , the median OS in patients with DNMT3A mutation was lower than that of patients with DNMT3A wild type [4.0 months (95% CI 3.8-4.2) vs 6.3 months (95% CI 2.4-10.2) , P =0.041) ]. Multivariate analysis showed that age ≥60 years and white blood cell count ≥100×10(9)/L were independent risk factors for OS and PFS, while CR after two courses of treatment and hematopoietic stem cell transplantation were independent prognostic favorable factors for OS and PFS. Conclusion: In patients with AML (non-M(3)) , IDH gene mutations often coexisted with other gene mutations, and different subtypes and accompanying gene mutations of IDH have different prognostic significance.

Objective: To investigate the expression of CD123 in patients with acute myeloid leukemia (AML) and its relationship between clinical features, concomitant fusion gene or gene mutation, efficacy and prognosis., Methods: 365 patients with newly diagnosed AML (except M3) treated in the First Affiliated Hospital of Zhengzhou University were enrolled and retrospective analysis, and multi-parameter flow cytometry was performed to detect the expression of CD123 in myeloid leukemia cell population. CD123≥20% was defined as positive. Clinical features, concomitant fusion gene or gene mutation, efficacy and prognosis of CD123 + and CD123 - patients were compared and analyzed., Results: The positive rate of CD123 in 365 newly diagnosed AML patients was 38.9%. Compared with the CD123 - group, the white blood cell count (WBC), lactate dehydrogenase (LDH) level and bone marrow blast cell ratio were higher in the CD123 + group, and the ratio of NPM1 and DMNT3a gene mutations and the CBFβ-MYH11 fusion gene was significantly increased, while the ratio of CEBPA gene mutation and AML-ETO fusion gene was significantly reduced. The rate of first inducing complete remission and total remission in CD123 + group was significantly lower than that in CD123 - group. There was no significant difference in recurrence rate between the two groups (P>0.05). Survival analysis showed that in 77 AML patients with normal karyotype and intermediate risk, the 2-year overall survival (OS) rate and event-free survival (EFS) rate of the CD123 + group were significantly lower than those of the CD123 - group. Multivariate analysis showed that CD123 was an independent prognostic risk factor for OS and EFS in AML patients with normal karyotype and intermediate risk., Conclusion: CD123 positive indicates that AML patients have higher tumor burden and are more difficult to reach remission. It is an independent risk factor for OS and EFS in patients with normal karyotype and intermediate risk, which is important to evaluate the prognosis of patients with AML without specific prognostic marker.

Objective: To analyze the characteristics of gene mutation in adult ALL and its clinical significance., Methods: Clinical data of 134 primary adult ALL patients and DNA sequencing results of 16 kinds of gene mutation were collected. The characteristic of gene mutation and clinical significances were statistically analyzed., Results: In 31 cases of 134 ALL cases (23.13%) the gene mutations were detected as follows: 19 cases of 114 B-ALL cases (16.67%), 11 cases of 19 T-ALL cases (57.89%) and 1 case of T/B-ALL. The incidence of T-ALL gene mutation was significantly higher than that of B-ALL (χ 2 =13.574, P<0.01). Twelve gene mutations were found, and the mutation rates was IL7R, NOTCH1, FLT3, TP53, FBXW7, PAX5, IKZF1, CREBBP, JAK3, JAK1, PHF6 and PTEN from high to low. Among 108 non-transplantable follow-up patients there was no significant difference in 1-year overall survival rate (49.7% vs 67.4%) and median non-recurrence survival time (214 days vs 260 days) between the gene mutation group (23 cases, 21.30%) and the non-mutation group(85 cases, 78.70%). There was a significant difference in 1-year survival rate between NOTCH1 mutation group (4 cases, 3.77%) and non-mutation group (102 cases, 96.23%) (50.0% vs 65.8%,χ 2 =9.840, P<0.01)., Conclusion: There may be multiple gene mutations in adult ALL patients. IL7R and NOTCH1 are the most common gene mutations and NOTCH1 mutation may indicate poor prognosis. Detection of gene mutations is helpful to understand the pathogenesis of ALL and evaluate the prognosis of adult ALL patients.

Long non-coding RNA (lncRNA) ANRIL has been reported to be closely related to the relapse of multiple myeloma patients. However, the functional role and underlying mechanism of lncRNA ANRIL in multiple myeloma are not known. This study aims to investigate the biological function of lncRNA ANRIL in multiple myeloma. In this study, compared with normal tissues from healthy donors, lncRNA ANRIL and HIF-1α expressions were up-regulated in tumor tissues from multiple myeloma patients. miR-411-3p expression was down-regulated in tumor tissues from multiple myeloma patients. Besides, lncRNA ANRIL can interact with miR-411-3p. HIF-1α was confirmed to be a target of miR-411-3p. Correlation analysis showed that lncRNA ANRIL expression was negatively correlated with miR-411-3p expression. HIF-1α expression was negatively correlated with miR-411-3p expression. Further transfection experiments showed that knockdown of ANRIL or overexpression of miR-411-3p significantly inhibited cell proliferation, tumor formation ability and tumor stem cell like property, promoted cell apoptosis in vitro. Finally, miR-411-3p mimic reduced tumor volume, improved survival rate, suppressed malignant proliferation and tumor stem cell like property in U266 xenograft model. Our results demonstrate that lncRNA ANRIL mediated by miR-411-3p promotes the malignant proliferation and tumor stem cell like property of multiple myeloma through regulating HIF-1α., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: To investigated the clinical and pathological characteristics of related-renal damage in patients with POEMS syndrome., Methods: Five patients diagnosed as POEMS syndrome in our hospital were selected. Their clinical manifestation, pathological characteristics of kidney and laboratory examination were analyzed retrospectively. Among the 5 patients, three males and two females with a median age of 50 years old. The mean interval before diagnosis was 13.0±7.2 months., Results: All the patients showed neuropathy, endocrinopathy, monoclonal plasma cell-proliferative disorder, skin changes and extravascular volume overload, in which 4 patients showed organomegaly. Proteinuria was found in 5 patients, and microhematuria was found in 4 patients. Moreover, 4 patients showed an elevated blood urea, while 2 patients showed creatinine elevation. 1 patient at chronic kidney disease (CKD)-G1 stage, 2 patients at CKD-G2 stage, and 1 patient at CKD-G3b stage, moreover, 1 patient at CKD-G5 stage. Endothelial injury and mesangial lesion were the main characteristics of renal pathology. 3 patients were pathologically diagnosed as thrombotic microangiopathy kidney damage, while 2 patients as light chain amyloidosis., Conclusion: POEMS syndrome is a multi-systemic disease with complex clinical manifestations. 5 patients had different degrees of renal insufficiency. Endothelial injury and mesangial lesion are the main features of renal pathology.

Objective: To investigate the clinical characteristics and prognosis in adult acute myeloid leukemia (AML) patients with FLT3-ITD and CEBPA double-mutated (CEBPAdm) co-mutation. Methods: Clinical data and prognostic factors were retrospectively analyzed in adult AML patients with FLT3-ITD and CEBPAdm co-mutation at The First Affiliated Hospital of Zhengzhou University from January 2016 to September 2018. Results: Among 599 non-acute promyelocytic leukemia (APL) patients, 268 received gene mutation detection, who were divided into 4 groups including 19 FLT3-ITD positive (FLT3-ITD(+)) and CEBPAdm positive (CEBPAdm(+)) cases (group A) , 84 FLT3-ITD(+) and CEBPAdm(-) cases (group B) , 95 FLT3-ITD(-) and CEBPAdm(+) cases (group C) , 70 double negative mutation cases (group D) . Gender, platelet count, FAB classification, induction treatment regimen and fusion gene mutation were comparable among four groups ( P >0.05) , while age onset, peripheral white blood cell (WBC) count, hemoglobin, percentage of blasts in peripheral blood, percentage of blasts in bone marrow, complete remission rate (CR(1) rate) after the first induction chemotherapy, the relapse rate, the median progression-free survival (PFS) time, and median overall survival (OS) time were significantly different between groups ( P <0.05) . When compared in pairs, gender, age onset, hemoglobin, platelet count, FAB classification in group A were not statistically different compared to group B, C and D ( P >0.05) , while patients in group A had higher WBC count, blasts in peripheral blood, minimal residual disease (MRD) in bone marrow. The CR(1) rates of group A, B, C, and D were 50.0%、32.4%、59.8%、39.0% respectively ( P =0.003) , and the relapse rates were 55.6%, 50.0%, 21.1%, 40.0% ( P <0.001) . As to survival, the median OS in each group was 6.25, 3.0, 15.5, 10.5 months respectively ( P <0.001) , and the median PFS was 5.0, 4.0, 10.0, 6.7 months ( P =0.032) . Conclusion: Adult AML patients with FLT3-ITD and CEBPAdm co-mutation have a higher leukemia load and low CR(1) rate, which translates into poor prognosis with high relapse rate and short survival time.

Objective: To compare the gene mutational spectrum between elderly and young adults with acute myeloid leukemia(AML) based on next generation sequencing(NGS)., Methods: The specimens of 250 AML patients in first affiliated hospital of Zhengzhou University from January 2018 to November 2018 were collected and analyzed retrospectively. The mutation of 22 related genes were detected by using AML NGS chips. Then, the differences between elderly (≥60 years old) and young adults (＜60 years old) were compared., Results: The most frequent mutations of 250 patients were as follows: NPM1(22.4%), FLT3-ITD(18.8%), NRAS(17.2%), DNMT3A(14.4%), TET2(11.6%), IDH2(9.6%), Biallelic CEBPA(8.8%), Moallelic CEBPA(8.4%), KIT(8.4%), RUNX1(7.6%), IDH1(7.6%), ASXL1(6.0%), U2AF1(5.2%), SRSF2 (3.2%), SF3B1(3.2%), TP53(2.4%), KRAS(2.0%). The NPM1, CEBPA, DNMT3A mutation significantly increased in intermediate prognosis group while KIT significantly increased in favourable prognosis group. The TET2 and IDH2 mutation rate in elderly patients were significantly higher than that in young patients (21.8% vs 8.7%) (χ 2 =7.180, P=0.007) and (20.0% vs 6.7%) ( χ 2 =8.788, P=0.003) respectively. Compared with young patients, the frequencies of DNA methylation and demethylation mutations (including DNMT3A, TET2, IDH1, IDH2) and RNA splicing enzyme mutations (inc-luding SRSF2, SF3B1, U2AF1, ZRSR2) in elderly patients significantly increased(67.3% vs 36.4%) (χ 2 =16.653, P=0.000) and (23.6% vs 8.7%)(χ 2 =9.041, P=0.003) respectively., Conclusion: The gene mutational spectrum in elderly and young adult AML shows heterogeneity. Compared with young adults, the frequencies of DNA methylation and demethylation mutations and RNA splicing enzyme mutations in elderly patients significantly increase.

Objective: To analyzed the clinical characteristics and prognosis of patients with H7N9 avian influenza. Methods: The baseline characteristics, clinical manifestations, treatments, laboratory and imaging findings were collected and analyzed for 20 patients with H7N9 avian influenza admitted to the First Affiliated Hospital of Nanchang University from December 2016 to March 2017. According to the final clinical outcome, the patients were divided into the death group and the survival group. Ten patients in the death group died, and 10 patients in the survival group were discharged. The data with normal distribution were analyzed by t test. The data with non-normal distribution were analyzed by Wilcoxon rank sum test. Results: Of the 20 patients, 13 were males and 7 were females, aging 40-82 years, with a mean age of (60±12) years. Twelve patients had a definite history of poultry exposure and 10 had chronic underlying diseases such as hypertension and diabetes. The clinical manifestations were mainly fever, cough, hemoptysis, respiratory distress, fatigue, etc. In the survival group, the platelet count was(167-315)×10(9)/L, while it was (78-152)×10(9)/L in the death group. The average white blood cell count was (7.78-11.52)×10(9)/L and (9.91-15.93)×10(9)/L in the survival and death groups respectively. The average value of lymphocyte count was (0.69-1.59)×10(9)/L and (0.58-0.86)×10(9)/L in the survival and death groups respectively. In the death group the glutamic-pyruvic transaminase (ALT) value was (14.0-352.0) U/L, the total bilirubin value was (6.9-34.5) μmol/L, the creatine kinase MB (CK-MB) was (16.0-162.0) U/L, the serum calcium value was (1.4-2.0) mmol/L, the C-reactive protein value was (33.1-414.0) mg/L, and the calcium reduction prime value was (0.6-100.0) μg/L. In the survival group,the ALT value was (25.0-181.0) U/L, the total bilirubin value was (4.8-25.9) μmol/L, the CK-MB value was (15.0-40.0) U/L, the serum calcium value was (1.9-2.4) mmol/L, the C-reaction protein value was (12.8-52.5) mg/L, and the procalcitonin value was (0.3-23.3) μg/L. Sixteen cases suffered severe pneumonia. Twelve patients received extracorporeal membrane oxygenation (ECMO), and 4 survived. The cause of death was mainly related to factors such as age, chronic underlying diseases and severity of illness. Conclusions: Human infection with H7N9 avian influenza virus was highly pathogenic, and prone to progress into severe pneumonia, with a high mortality. Decreased platelet count was associated with mortality ( t= 4.07, P= 0.001), predictive of patient outcome.

Background: Allogeneic stem-cell transplantation (SCT) is a well-established immunotherapeutic strategy for multiple myeloma (MM) with a potent and often sustained graft-vs.-myeloma effect. This multicenter investigation aimed to analyze the complications and survival of haploidentical SCT in patients with MM, and compare the main outcomes with matched-related donors (MRDs)., Methods: Haploidentical and MRD SCT was identified from a cohort of 97 patients with MM who received a myeloablative transplantation in 13 hospitals from May 2001 to December 2017. A matched-pair analysis was designed. For each haplo recipient, the recipients were randomly selected from the MRD group and were matched according to the following criteria: year of the hematopoietic SCT (±2 years), disease status at transplantation, and the length of follow-up., Results: Seventy cases received MRD and 27 received haploidentical transplantation. The two groups showed no significant differences regarding age, gender, cytogenetic risk, and diagnostic stage. The cumulative incidences of non-relapse mortality (NRM) at 1 and 3 years based on donor type were 20.5% (95% confidence interval [CI], 10.90-30.10%) and 24.2% (95% CI, 13.81-34.59%) for the MRD group and 16.80% (95% CI, 1.71-31.89%) and 28.70% (95% CI, 8.71-48.69%) for the haplo group, respectively. Cumulative incidence of NRM did not differ significantly between the two groups (χ = 0.031, P = 0.861). The cumulative incidences of progression-free survival (PFS) and 1 year and 3 years by type of donors were 59.8% (95% CI, 48.24-71.36%) and 45.4% (95% CI, 33.44-57.36%), and 65.6% (95% CI, 47.18-84.02%) and 26.8% (95% CI, 7.59-46. 01%) for MRD and haploidentical donor, respectively. Cumulative incidence of PFS did not differ significantly between the two groups (χ = 0.182, P = 0.670). In multivariate analyses, no statistically significant differences were observed between haploidentical and MRD for relapse, NRM, PFS, and overall survival. There were no statistically differences on main outcomes after haploidentical and MRD., Conclusion: Haploidentical SCT could be performed safely and feasibly for patients with MM in need.

Objective: To explore the reversal effect of pioglitazone (PIO) on multidrug resistance in K562/ADR cells and its mechanism., Methods: The proliferation inhibition rate, half inhibition concentration (IC 50 ) and drug-resistance reversal multipe were detected and the curve of proliferation inhibition rate was drawn by MTT assay, the transcription of PPARγ, CYP2C8 and CYP2J2 genes was detected by RT-PCR; the expression of PPARγ, CYP2C8 and CYP2J2 proteins was detected by Western blot., Results: The IC 50 of PIO on K562 and K562/ADR cells for 60 h was 326.7 μmol/L and 349.1 μmol/L respectively. The reversal multiple of 30 μmol/L PIO on ADR-resistance of K562/ADR cells was 6.4. After treatment of K562/ADR cells with PIO, the transcription of CYP2C8 and CYP2J2 and the protein expression of CYP2C8 and CYP2J2 significantly decreased, the transcription of PPARγ gene and the expression of PPARγ protein were not changed., Conclusions: Pioglitazone can reverse the adriamycin-resistance in K562/ADR cells that is closely related to the decrease of protein expression of CYP2C8 and CYP2J2. Pioglitazone is an effective multidrug resistance reversal agent for tumors.

Objective: To explore the changes of autophagic activity after resistance of U266 cells to bortezomib (Bor) and its mechanisms., Methods: The proliferation inhibition rate, 50% inhibitory concentration (IC 50 ), drug-resistance coefficient, drug-resistance reversed multiple by 3-methyladenine (3-MA) in U266 and U266/Bor cells treated with Bor were detected and calculated by using MTT method, then the proliferation inhibition curve was drawed. The Western blot was used to detect the expression of LC3-I, IC3-II, p-mTOR, Beclin-1, ATG5 and ATG7 proteins., Results: The Bor showed the its proliferation inhibition effect on U266 cells and U266/Bor cells, IC 50 of Bor on U266 and U266/Bor cells on 24 hours were 35.7 nmol/L and 526.5 nmol/L respectively; the drug-resistance coefficient was 14.7; the drug-resistance reversed multiple by 3-MA was 2.7. The expression of LC3-II, Beclin11, ATG5 and ATG7 in U266/Bor cells was higher than that in U266 cells; after the treatment with Bor for 24 h, the expression levels of LC3-II, Beclin-1, ATG5 and ATG7 in U266 cells all decreased, as compared with levels before treatment; while the expression levels of LC3-II, Beclin-1, ATG5 and ATG7 in U266/Bor cells were higher than those before treatment. There were no significant difference of p-mTOR expression among U266, U266+Bor, U266/Bor, U266/Bor+Bor cells., Conclusion: The increase of autophagy closely relates with resistance of U266 cells to bortezomib, moreover with up-regulation of Beclin-1, ATG5 and ATG7 expression.

The high frequency of bird strikes at night during the migration season is a remarkable characteristic of bird strikes at airports. Understanding the nocturnal migration patterns of birds is important for improving the methods to prevent bird strikes at night. In this study, we combined the methods of mist-net capture and sound recording to examine the composition of bird species and the patterns of nocturnal migration at Taoxian Airport. We found that 56 species of birds (88.9% of the total) migrated at night and mainly migrated after midnight. There were obvious temporal dynamics and sequence in migration. The time of spring migration was more concentrated and the migration peaked in mid-May, with Coturnix japonica, Lanius cristatus, Emberiza fucata, Saxicola torquatus, Caprimulgus indicus and Phylloscopus inornatus as the dominant species. The migration pattern was more dispersed in autumn and the peak of migration was in late September to early October, and the main species were C. japonica, Turdus hortulorum, Anthus cervinus, Scolopax rusticola, Locustella lanceolata and Emberiza spodocephala. Based on the Bird Hazard Risk Assessment, there were mainly two species with high risk (C. japonica and L. cristatus) in spring migration and four species with high risk (C. japonica, Athene noctua, T. hortulorum and S. rusticola) in autumn migration. We proposed several strategies for the prevention of bird strike based on the composition of migratory birds, migration dynamics, migration rhythm and species risk level, which could serve as references for bird strike prevention at Taoxian Airport.

Objective: To investigate the expression of long non coding RNA RP11-69I8.3 in acute leukemia and its clinical significance., Methods: lncRNA RP11-69I8.3 expression was detected by RT-PCR in bone marrow samples from 17 healthy controls, 32 newly diagnosed AML patients and 32 newly diagnosed ALL patients, and 25 ALL patients of complete remission after chemotherapy. Meanwhile, the clinical data were collected and the relation of lncRNA RP11-6918.3 expression with the clinical characteristics was analyzed., Results: Compared with the control group, there was no significant difference in the expression of lncRNA RP11-69I8.3 in AML group(P>0.05). lncRNA RP11-69I8.3 lowly expressed in untreated ALL group(P=0.001). Compared with the de novo ALL group, lncRNA RP11-69I8.3 was highly expressed in complete remission ALL group (P<0.013). In 32 de novo ALL patients,the expression of lncRNA RP11-69I8.3 in children was significantly lower than that in adult(P=0.017). There was no correlation of the expression of lncRNA RP11-69I8.3 with the sex, WBC count, HB level, Plt count, LDH level, T or B type, ratio of bone marrow blast cell, BCR/ABL and WT1 fusion gene expression, chromosome karyotype, extramedullary infiltration, whether complete remission after one chemotherapy, whether relapse. In 26 B-ALL patients, there was no correlation between lncRNA RP11-69I8.3 and the immunophenotype., Conclusion: The expression of lncRNA RP11-69I8.3 in the untreated AML is not significantly different from the control group. lncRNA RP11-69I8.3 is low expressed in ALL group, highly expressed in ALL group with complete remission. In untreated ALL, the expression of lncRNA RP11-69I8.3 in children is significantly lower than that in adult. In B-ALL patients, the lncRNA RP11-69I8.3 is not relevant with the immunophenotype.

Objective: To evaluate the efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) from different donors as first-line treatment for children and adolescents with severe aplastic anemia (SAA) . Methods: The clinical data of 79 children and adolescents with SAA diagnosed from January 2013 to December 2016 in Henan Province were retrospectively analyzed. There were 50 males and 29 females, with a median age of 14(4-18) years. 40 cases received matched sibling transplantation (MSD-HSCT), 17 with unrelated donor transplantation (UD-HSCT), and 22 with haploidentical transplantation (haplo-HSCT). Results: The comparison of MSD-HSCT, UD-HSCT, haplo-HSCT groups was conducted and the median times of neutrophils engraftment were statistically significant [12(9-25) d, 14(10-22) d, 16(11-26) d, respectively ( χ 2 =13.302, P =0.001)], but no difference in+30 d engraftment rate [97.3%(36/37), 100%(15/15), 100%(20/20), χ 2 =0.959, P =0.619]. The median times of PLT engraftment were not statistically significant [14(6-34)d, 16(7-32)d, 19(10-34)d, respectively, χ 2 =5.892, P =0.053], and the +30 d engraftment rate had no difference [97.3%(36/37), 100%(15/15), 100%(20/20), χ 2 =0.959, P =0.619]. The post-transplant infection rate showed no statistically significance [35.0% (14/40), 29.4% (5/17), 45.5% (10/22), χ 2 =1.158, P =0.560], as well as the incidences of aGVHD, grade III/IV aGVHD and cGVHD( χ 2 =0.230, P =0.891; χ 2 =2.628, P =0.269; χ 2 =3.187, P =0.203). The two-years OS rate was not statistically significant respectively [(77.1±6.7)%, (70.6±11.1)%, (77.3±8.9)%, χ 2 =0.330, P =0.845]. Severe post-transplant infection ( RR =4.617, P =0.009), grade Ⅲ/Ⅳ aGVHD ( RR =2.707, P =0.048) were independent risk factors for OS. Conclusion: The overall efficacy of MSD-HSCT, UD-HSCT and haplo-HSCT as first-line therapy for children and adolescents with SAA/VSAA is comparable.

Objective: To investigate the expression of long-chain non-coding RNA RP11-87C12.5 in acute lymphocytic leukemia and its clinical significance., Methods: LncRNA RP11-87C12.5 expression was detected by RT-PCR in bone marrow samples from 17 control group, 33 newly diagnosed ALL patients and 26 complete remission ALL patients after chemotherapy, at the same time the clinical data were collected and the clinical significance of IncRNA RP11-87C12.5 expression was analyzed., Results: Compared with control group, lncRNA RP11-87C12.5 expression increased in newly diagnosed ALL group (P=0.021); compared with newly diagnosed ALL group, IncRNA RP11-87C12.5 expression decreased in complete remission ALL group (P=0.039). lncRNA RP11-87C12.5 expression in newly diagnosed ALL group did not relate with sex, age, T or B type, WBC count, Hb level, Plt count, LDH level, bone marrow blast ratio, BCR/ABL fusion gene expression, chomosome karyotypes, WT1 gene, extrameanllary infiltration or no,complete remission or no after one chemotherapy and relapse or no. In 27 cases of ALL, IncRNA RP11-87C12.5 expression significantly increased in cCD79a low expression group, compared with cCD79a high expression group (P=0.004). IncRNA RP11-87C12.5 expression did not relate with other CD molecules of immunoclassification., Conclusion: The expression of LncRNA RP11-87C12.5 is high in newly diagnosed ALL group and low in complete remission ALL group. In B-ALL, the expression of IncRNA RP11-87C12.5 significantly enhances in cCD79a low expression group. In newly diagnosed ALL group, compared with low expression group, lncRNA RP11-87C12.5 high expression group have higer remission rate and relapse rate, but the difference was not statistically significant.

Objective: To investigate the expression of N-cadherin in bone marrow leukemic cells derived from acute leukemia patients and its clinical significances., Methods: A total of 113 patients with acute leukemia were enrolled in this study. Flow cytometry was employed to detect the expression of N-Cadherin in bone marrow leukemic cells from acute leukemia patients and the relationships between the N-cadherin expression and the clinical characteristics of patients with acute leukemia were analyzed., Results: The expression of N-Cadherin in bone marrow leukemic cells deriveted from patients with acute leukemia was variable with 0%-99.7%. For adult AML patients, the positive rate of CD34 in N-cadherin + group was significantly higher than that in N-cadherin - group(67.39% vs 33.33%)(P=0.013), while the differences of total CR rate and rate of CR after 1 cycle of induction treatment were not significant between these 2 groups(P>0.05). As to ALL patients, N-cadherin + group had significant lower WBC count (21.31±7.07 vs 51.10±23.69)(P=0.008) and lower percentage of peripheral blood blast (43.22±5.75% vs 66.45±5.65%)(P=0.015). The CR rate after 1 cycle of induction treatment and rate of overall CR were lower and the relapse rate was higher in N-cadherin + ALL group than those in N-cadherin - ALL group, but the differences were not significant (P>0.05). For childhood ALL, the positive rate of CD33 in N-cadherin + group was significantly higher than that in N-cadherin - group(47.62% vs 0%)(P=0.012). The relapse rate was higher in N-cadherin + group than that in N-cadherin - group (30.00% vs 0%)(P=0.115). The median survival time, 3-year overall OS rate and 3-year relapse-free survival rate in N-cadherin - groups of adult AML, non-M3 AML, ALL and chidhood ALL paients were superior to N-cadherin + groups, but the differences were not significant., Conclusion: The expression of N-cadherin in bone marrow leukemic cells relates to some clinical features of patients with acute leukemia and to some extent has inferior effect on survival of patients with acute leukemia.

Objective: To analyze the clinical characteristics of cytomegalovirus(CMV) infection after allogenic hematopoietic stem cell transplantation(allo-HSCT) and the effect of preemptive therapy., Methods: A total of 134 patients who underwent allo-HSCT from March 2010 to March 2015 in the Department of Hematology of our hospital were enrolled in this study. The CMV infection rate, the median time of CMV infection occurence, and the risk factors for CMV infection after allo-HSCT, the response rate of preemptive treatment and the median time of CMV-DNA turning negative were analyzed. Five-year overall survival rate was compared between the patients with or without CMV infection., Results: The incidence of CMV viremia was 55.2％(74／134), and the median time for the CMV with CMV-DNA positive for the first time was 34 days(14-283) after allo-HSCT．Both univariate and multivariate analysis showed that the thymoglobulin(ATG) used in conditioning regimen and Ⅱ-Ⅳ grade of aGVHD were the risk factors for CMV viremia. After preemptive treatment the 85.1% of patient with CMV viremia turned negative, and the median time of CMV-DNA turning negative were 15 days(5-82), only 2 patients died of CMV pneumonia. Five-year overall survival rate of the patients with or wihout CMV viremia was 49% and 66.3% respectively, and the difference between the 2 groups was significant(P=0.041）., Conclusion: The ATG used in conditioning regimen and Ⅱ-Ⅳ grade of aGVHD may increase the incidence of CMV infection after allo-HSCT, and the preemptive thrapy can effectively prevent the CMV viremia turning to CMV disease.

Objective: To explore the clinical features of multiple myeloma with different renal pathology, and to evaluate its prognosis., Methods: Clinical features and prognosis of 46 multiple myeloma patients with different renal pathology were analyzed retrospectively. According to renal pathology, the 46 patients were divided into 3 groups: cast nephropathy (24 cases), amyloidosis (15 cases) and other type (7 cases)., Results: By durie-Salmon staging system, 70.8% cases (17/24) in the cast nephropathy group were in Phase III, 90.9% (20/24) were in subtype B, while in amyloidosis group 53.3% (8/15) were in Phase I, 40% (6/15) were in subtype B, and in other types group, 71.4% (5/7) were in phase III, 57.1% (4/7) were in subtype B, the differences among them were statisticaily significant (P < 0.05). In cast nephropathy group, the monoclonal immunoglobulin could not be detected in 75% (18/24) cases, which was light chain type, while immunoglobulin in amyloidosis and other type groups were mainly IgG type in 73.3% (11/15) and 71.4% (5/7) respectively, the difference among them also was statistically significant (P < 0.05). The median survival time of patients in cast nephropathy group was 11 months, while that in amyloidosis and other type groups was 19 and 18 months, the differences among 3 groups were not significant (P > 0.05)., Conclusion: In renal pathologic types, the cast nephropathy is the most common, followed by amylordosis. The multiple mycloma patients with defferent renal pathology show different clinical features. The multiple myeloma patients with renal amyloidosis have slighter clinical manifestations possibly with a better prognosis. Meanwhile, the non-amyloidosis types, especially cast nephropathy may predict a more serious manifications with poor prognosis.

Objective: To evaluate the clinical characteristics of multiple myeloma (MM) combined with renal amyloidosis and its curative efficacy and prognosis., Methods: The clinical data of 22 cases of newly diagnosed multiple myeloma combined with renal amyloidosis treated in our hospital from November 2011 to July 2015 were analyzed retrospectively., Results: According to Intenational Staging System (ISS), among above-menthioned 22 patients the ISS II accounted for 77.2% (17/22), ISS III accounted for 22.8% (5/22). The patients with renal impairment accounted for 36.4% (8/22), with anemia 40.9% (9/22), with serum album < 35 g/L 86.4% (19/22), with urinary protein positive 100% (22/22). The evaluation of the curative efficacy of the 22 cases was as follows: CR 13.6% (3/22); VGPR 4.5% (1/22); PR 22.8% (5/22); SD 45.5% (10/22); PD 13.6% (3/22). Out of 9 patients with effective treatment, 3 cases (3/9, 33.3%) achieved "improved" in renal amyloidosis, 4 cases (4/9, 44.5%) achieved stable in renal amyloidosis, 2 cases (2/9, 2%) achieved "worsened" in renal amyloidosis. Among 17 cases who were followed up, 7 cases died, 10 cases survived, the average duration of follow-up for these cases was 11 (1-37) months, the median overall survival (OS) time was 19 (95% CI 9.2-28.8) months., Conclusion: MM with renal amyloidosis is rare, refractory and has a poor prognosis. Whether there is impairment of kidney function or not, renal amyloidosis shall be taken into consideration if the MM patients got massive proteinuria especially nephritic syndrome. Bortezomib may improve the curative efficacy.

Polydatin (PD), a natural precursor of resveratrol, has a variety of biological activities, including anti‑tumor effects. However, the underlying molecular mechanisms of the anti-cancer activity of PD has not been fully elucidated. The present study demonstrated that PD significantly inhibited the proliferation of the MOLT-4 leukemia cell line in a dose‑ and time-dependent manner by using Cell Counting Kit‑8 assay. PD also dose-dependently increased the apoptotic rate and caused cell cycle arrest in S phase in MOLT‑4 cells, as revealed by flow cytometry. In addition, PD dose-dependently decreased the mitochondrial membrane potential and led to the generation of reactive oxygen species in MOLT-4 cells. Western blot analysis revealed that the expression of anti‑apoptotic protein B-cell lymphoma 2 (Bcl-2) was decreased, whereas that of pro‑apoptotic protein Bcl‑2‑associated X was increased by PD. Furthermore, the expression of two cell cycle regulatory proteins, cyclin D1 and cyclin B1, was suppressed by PD. Of note, the pro‑apoptotic and cell cycle‑inhibitory effects of PD were potentiated by Janus kinase 2 (JAK2) inhibition. In conclusion, the results of the present study strongly suggested that PD is a promising therapeutic compound for the treatment of leukemia, particularly in combination with JAK inhibitors.

Objective: To investigate the CD25 expression in patients with acute myeloid leukemia (AML) and its significance., Methods: Clinical data of 168 newly diagnosed AML patients (except APL) were collected. The expression of CD25 in AML patients and its clinical characteristics were retrospectively analyzed., Results: The leukemia cells of 29 out of 168 cases (17.26%) expressed CD25 antigen. Most of CD25 positive AML patients were occurred in patients with unfavourable or normal karyotype, higher WBC and Plt count at diagnosis and higher percentage of blasts in peripheral blood and bone marrow. Compared with CD25(-) AML patients, CD25(+) AML patients had lower CR rate (the CR rate of 1 course of treatment were 49.02% and 16.00%, respectively, P < 0.05, the CR rate of 2 courses of treatment were 74.60% and 46.67%, respectively, P < 0.05), and the OS time of CD25(+) AML patients were obviously shorter (P < 0.05). The OS in CD25(+) AML patients with unfavorable karyotype were not significantly different from that in patients with intermediate karyotype (P < 0.05)., Conclusion: The CD25(+) AML patients have some typical clinical features, and the expression of CD25 in AML is an risk factor independent of the chromosome karyotype in terms of low complete remission rate and short survival time.

Objective: To investigate the expression of N-Cadherin in the patients with multiple myeloma (MM) and to explore its clinical significance., Methods: A total of 64 patients with multiple myeloma were enrolled in this study. The expression of N-Cadherin in bone marrow CD38⁺/CD138⁺ cells from multiple myeloma patients was detected by flow cytometry. The relationship between N-Cadherin expression and clinical prognostic factors was analyzed., Results: Among 64 cases of MM, the expression of N-Cadherin in 17 patients (26.56%) was high (> 20%), while that in 47 cases (73.44%) was low (< 20%); The differences of N-Cadherin expression in disease staging and classification, known prognostic factors, myeloma cell antigen expression and bone damage between patients with high and low N-Cadherin expression were not statistically different; the difference N-Cadherin expression in genetic abnormalities such as D13S319 deletion, RB1 deletion and IGH gene rearrangement between above-methioned two groups was not significant. The 1q21 amplification rate in the group with high expression of N-Cadherin was enhanced significently; the overall survival (OS) times of patients with abnormally high and low expression levels of N-Cadherin were 26.7 months and 55.5 months respectively, and the difference was statistically significant (P < 0.05)., Conclusion: The high expression of N-Cadherin in multiple myeloma may be one of the indicator for poor prognosis of MM, which may be related with 1q21 amplification.

The aim of this study was to explore the reversing effect of cinobufacini on multidrug resistance of Raji/ADR cells and its mechanisms. The growth inhibitory rate, half inhibitory concentration (IC50), reversing multiples to adriamycin- resistance were detected by MTT, and the curve of growth inhibitory rate was drawn; the MDR-1 and MRP-1 gene transcription was determined by RT-PCR; the expressions of P-gp and MRP-1 proteins were assayed by Western blot and flow cytometry. The results showed that the inhibitory rates of cinobufacini on Raji and Raji/ADR cells at 72 h were 75.6% and 69.3% respectively, the IC50 were 3.9 mmol/L and 4.6 mmol/L without significant difference (P > 0.05). The reversing multiples to adriamycin-resistance were 255.7 multiples, the transcription of mdr-1 and mrp-1 genes and the expression of P-gp and MRP-1 proteins significantly decreased (P < 0.05) in Raji/ADR cells after the treatment with cinobufotalin. It is concluded that cinobufotalin can reverse the adriamycin-resistance in Raji/ADR cells and the expression of P-gp and MRP-1 proteins were down-regulated through the transcriptional pathway. The cinobufotalin is an effective reversal agent for the multidrug resistance of tumors.

Objective: We aim to evaluate the clinical efficacy of a modified busulfan and cyclophosphamide (BU/CY) conditioning regimen for allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the treatment of hematologic malignancies., Methods: A total of 45 patients with hematologic malignancies were treated using stem cell transplantation between March 2007 and June 2012. All the patients received a modified BU/CY conditioning regimen before transplantation. The outcomes of the patients were followed up including mortality, survival, relapse, and complications., Results: The median of follow-up duration was 527 days. All the patients who received modified BU/CY conditioning regimen achieved hematopoietic recovery successfully. Among the patients, 24 were survived without complications, 5 had relapsed hematologic malignancies, and 16 died. The median time to leucocyte engraftment was 14 days and to platelet engraftment was 12 days. Acute graft-versus-host disease (aGVHD; grades I-IV) occurred in 15 patients (30%). The cumulative incidence of grades I aGVHD was 22.2% (10 patients), grades II was 6.7% (3 patients), and grades III-IV was 4.4% (2 patients). Among 40 appreciable patients, 8 (20%) developed chronic GVHD. The incidence rate of hemorrhagic cystitis and veno-occlusive disease were 15.5% and 2.2%, respectively., Conclusions: The modified BU/CY conditioning regimen for allo-HSCT is effective and safe for the treatment of hematologic malignancies., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Objective: To investigate the risk factors, clinical features, efficacy and adverse reactions in patients of hematologic diseases with invasive fungal infections (IFI)., Methods: The risk factors and clinical features were retrospectively analyzed to compare the efficacy and safety of itraconazole with amphotericin B in treatment of IFI in 76 patients with hematologic diseases., Results: Of the 76 patients, 68 (89.5%) used broad-spectrum antibiotics, 64 (84.2%) were treated with more than 2 courses chemotherapy, 43 (56.6%) were under agranulocytosis, 34 (44.7%) were using glucocorticoid for long terms, 27 (35.5%) were with peripheral or central venous catheter. The overall effective rates of itraconazole and amphotericin B were 60.5% and 61.5% respectively (P = 0.929). There was a significant difference between itraconazole and amphotericin B in hypokalemia (14.0% vs 42.4%, P = 0.005) while no other differences in adverse reactions were found., Conclusions: The risk factors of patients in hematologic diseases with IFI include chemotherapy, using broad septum antibiotics and agranulocysis. The therapeutic effect of itraconazole and amphotericin B in treatment of IFI is similar. The adverse reactions of itraconazole is less and slighter than amphotericin B.

Mating systems, as an evolutionary stable strategy, play an important role in animal reproductive process and result from an animal's adaption to their environment, including their inter-specific environment. In the 1980s, extrapair paternity (EPP) was first noted in the eurychoric species, the Great Tit, Parus major. As earlier studies indicated, morphology, physiology, behavior, ecological characteristics and mating systems of eurychoric species differ greatly between areas or populations. Accordingly, we analyzed the mating system of the Great Tit (P.m.minor) in Fairy Cave National Nature Reserve, Liaoning, China. We collected total parent-offspring blood samples from 22 broods. We used 8 hypervariable loci, which were selected from 11 reported microsatellite loci for paternity test. In conjunction with the known genetic pattern of the female parent, the accuracy of the paternity testing reached 99.98% with this genetic data. Results of paternity testing showed that 7 of 22 broods (31.8%) had extra-pair nestling, with 16 of 197 nestlings (8.12%) a result of extra-pair fertilizations. The EPP rate of the Great Tit we noted in Liaoning is obviously lower than those in other passerine forest birds (less than 10%). Though between 55.6% and 9.1% extrapair offspring were found among the different nests, we were, however, unable to find any explanatory rule.

Objective: To elucidate the clinical features, response rate, prognosis and clonal evolution of aplastic anemia (AA) with macrocytic anemia (mAA)., Methods: The clinical features at initial diagnosis and data in follow up of mAA hospitalized from January 2000 to October 2011 were analyzed retrospectively., Results: (1) Of 153/568 (26.9%) cases of mAA at initial diagnosis, 114(74.5%)were non-severe AA (NSAA), 39(25.5%)severe AA (SAA) and 0 very severe AA (VSAA), while the proportion was 16.2%, 45.2%, and 38.6% in 376 normocytic anemia AA (nAA), and the difference is statistically significant(χ(2) = 181.390; P = 0.000). The median age of mAA was significantly higher than that of nAA \[30(4 - 70)years vs 19 (3 - 68) years, P = 0.001\]. (2) There were no statistical difference in hemoglobin, absolute neutrophil count (ANC), platelet count (PLT), response rate after 6 months treatment and overall survival (OS) between mAA and nAA grouped in SAA and NSAA respectively. In SAA, the reticulocyte count (Ret) of mAA was significantly higher than that of nAA \[23.90(2.99 - 61.00)×10(9)/L vs 13.1(0 - 70.60)×10(9)/L, P = 0.000\] and the proportion of erythroid cells in bone marrow of mAA was also higher \[23.5 (0 - 58) vs 14.5 (0 - 65), P = 0.043\], while they did not differ significantly in NSAA. (3) The proportion of AA with PNH clones or abnormal cytogenetics did not differ significantly in mAA and nAA groups before treatment. The incidences of AA evolved to PNH in mAA and nAA was not statistically significant (7/153 vs 9/376, χ(2) = 1.099, P = 0.294) and so was the incidence of evolution to MDS/AML(3/153 vs 13/376, χ(2) = 0.399, P = 0.528)., Conclusion: In presented with macrocytic anemia at initial diagnosis of AA, higher proportion of NSAA, elderly age, higher Ret and proportion of erythroid cells are features, but being no statistical difference in the response rate, OS, and proportion of clonal evolution.

This study was purposed to analyze the clinical features and evaluate the efficacy of thalidomide combined with VAD regimen for treatment of osteosclerotic myeloma (POEMS syndrome). The data of 27 patients with POEMS syndrome in the First Affiliated Hospital of Zhengzhou University were analyzed retrospectively, including clinical manifestations, laboratory tests, treatments and prognosis. The results showed that the polyneuropathy was observed in 27 patients (27/27), hepato-spleno-lymphadenectasis was found in 15 patients (15/27), endocrinopathy was found in 24 patients (24/27), skin changes was observed in 22 patients (22/27). M protein was found in 23 patients (23/27); in addition to these clinical manifestations, the papilledema serous cavity effusion and sclerotic bone lesion were also frequently observed in patients with POEMS syndrome. The remission rates of treatment of POEMS syndrome with thalidomide combined with VAD regimen for organomegaly, edema, skin changes, and endocrinopathy were 60, 58.3, 41 and 45.8 respectively. The level of serum M protein and the nervous system ODSS value decreased greatly after treatment (P < 0.01). It is concluded that the clinical characteristics of POEMS syndrome are complicated and easy to be misdiagnosed, and the evidence of monoclonal plasma cell hyperplasia should be actively searched for those patients whose serum M protein is negative. Thalidomide combined with VAD regimen for treatment of patients with POEMS syndrome has advantages such as significant curative effects, less side-effects, good tolerance, and higher safety and can be chosen as a preferred approach.

The purpose of this study was to investigate the immunophenotyping characteristics of adult acute lymphoblastic leukemia (ALL) patients in groups of different ages. Immunophenotyping was performed in 260 ALL patients by flow cytometry using a panel of monoclonal antibodies and CD45/SSC gating. The results indicated that (1) all the 82 cases of T-cell acute lymphoblastic leukemia (T-ALL) expressed CD7 (100%) while the positive rate of CD2 remarkably decreased with aging. The positive rate of CD2 in patients aged 14 to 18 years (adolescents) was 91.67%, which is significantly higher than that in cases aged 19 to 35 years (young adults) and > 35 years (older adults) (65.71% and 43.48% respectively, p < 0.05); the positive rate of CD34 and HLA-DR increased with aging, there was significant difference of the HLA-DR expression between the older adults group (39.13%) and the other two groups (4.17% in adolescents and 11.43% in young adults respectively (p < 0.05). Moreover, there were significant differences of the myeloid antigen (MyAg) and CD13 expression between the older adults and younger adults (p < 0.05). (2) As to adult B-cell acute lymphoblastic leukemia (B-ALL), the positive rates of CD19 and HLA-DR in 178 cases were 100%; the positive rate of CD33 in young adults was significant higher than that in adolescents (p < 0.05), the differences of the other marker expressions failed to reach statistical significance in adult B-ALL patients. It is concluded that the immunophenotypes of adult T-ALL are evidently heterogeneous in different ages, and expression with more aberrant phenotypes indicates poor prognostic significance in patients older than 35 years. There is no significant association of immunophenotypes with ages among different age groups of adult B-ALL.

Background & Objective: Hematopoietic stem cell transplantation could improve the prognosis of malignant hematologic diseases. Peripheral blood stem cell transplantation (PBSCT) has been gradually used as an alternative to bone marrow transplantation (BMT). This study was to observe the efficacy of allogeneic PBSCT (allo-PBSCT) or autologous PBSCT (auto-PBSCT) on malignant hematologic diseases., Methods: From Jul. 2003 to May 2006, 53 patients with malignant hematologic diseases underwent PBSCT in the First Affiliated Hospital of Zhengzhou University. PBSCs were mobilized with granulocyte colony-stimulating factor (G-CSF) or chemotherapy combined with G-CSF. Auto-PBSCT group received infusion of CD34+ cells at a median of 3.0x10(6) cells/kg; allo-PBSCT group received infusion of CD34+ cells at a median of 6.2x106 cells/kg. MAC regimen was used in auto-PBSCT group as conditioning regimen; amended BU/CY regimen was used in allo-PBSCT group. Methotrexate (MTX) combined with cyclosporine A (CsA) and MMF was used for graft-versus-host disease (GVHD) prophylaxis. Antilymphocyte globulin (ALG) was used in 1 patient with 1 mismatched locus in allo-PBSCT group., Results: The median time for neutrophils to reach 0.5x10(9)/L and platelets to reach 20x10(9)/L were 13 days and 19 days in auto-PBSCT group, 12 days and 15 days in allo-PBSCT group. In allo-PBSCT group, grade I-III acute GVHD occurred in 31.4% cases, and chronic GVHD developed in 71.4% cases. The relapse rate was 38.9% in auto-PBSCT group and 5.7% in allo-PBSCT group. The 700-day disease-free survival rate (DFS) was 57.9% in auto-PBSCT group, and 69.5% in allo-PBSCT group., Conclusions: PBSCT can provide rapid hematopoietic reconstitution. It is a better choice for the cure of malignant hematologic diseases.

Objective: To evaluate cord blood stem cell transplantation (CBT) in the treatment of X-linked agammaglobulinemia, and observe the courses of the hematopoietic and immune reconstitution., Methods: A 14-year-old male patient with agammaglobulinemia received CBT from a 1/6 HLA-mismatched unrelated cord blood. The conditioning regimen was Bu/Cy/anti-CD3 antibody. CsA was given together with MMF and MTX for prophylaxis of GVHD. The patient received 0.42 x 10(8) nucleated cells/kg, containing 0.35 x 10(6) CD34(+) cells/kg., Results: The recipient showed hematopoietic reconstitution on day 30 post-transplantation when ANC was 0.5 x 10(9)/L and BPC 20 x 10(9)/L. Sex chromosome analysis showed engraftment (donor 46, XX/recipient 46, XY = 4:1) on day 45. The recipient's blood group changed from AB to O, IgG from 1.1 g/L to 3.5 g/L, sex chromosome from 46, XY to full 46, XX, and mature B cells in peripheral blood from 0 to 5% on day 100, indicating immune reconstitution. At the last follow-up of 360 days, the patient without acute or chronic GVHD showed normal hemogram and myelogram, IgG 13.5 g/L and 10% mature B cells in peripheral blood, indicating the hematopoiesis and immune persistent reconstitution. No acute or chronic GVHD was developed., Conclusion: This is the first case report of successful treatment of X-linked agammaglobulinemia by HLA-mismatched unrelated CBT.

The fate of the litter of dominant vegetation(willows and reeds) is one of the aspects studied in the frame of the project "Onderzoek Milieu Effecten Sigmaplan". One of the questions to be considered is how long the litter stays within the estuary. In this paper, the time the leaf litter (Salix triandra and Phragmites australis) stayed in the Schelde estuary was studied by using plant pigment as biomarkers with HPLC application. After analyzing the original data from the incubation experiment described by Dubuison and Geers (1999), the decomposition dynamics patterns of pigments were analyzed and described, and these decomposition dynamics patterns were used as calibration patterns. By using Spearman Rank Order Correlation, the calibration patterns of the pigments which were significant (p < 0.05) were grouped. In this way, several groups of the calibration patterns of pigment decomposition were achieved. The presence or absence of these groups of pigments (whether they can be detected or not from HPLC) was shown to be useful in determining the time the litter has stayed in the water. Combining data of DW and POC, more precise timing can be obtained.

20 fasting cats were used to investigate the propagation of Gastroelectrical Propagation Velocity (GPV) and the effect and nervous mechanism of acupuncture on it. The results are as follow: 1. GPV can be described as V = bo - b1x1 + b2x2. bo, b1 and b2: regression coefficient. x1: frequency of slow-wave. x2: amplitude of slow-wave. 2. GPV is changeable on normal condition, and it can be affected by stimulation of vagi or splantic nerve and by administration of pentagastrin i.v. or atropine i.v. with some change of not only x1, x2 but also b0, b1, b2. 3. Manual acupuncture and electrical acupuncture can affect GPV differently. 4. After vagotomy the effect of manual acupuncture on GPV was changed. All results suggest that GPV can be affected by acupuncture with complex mechanism including the change of propagation resistance and of propagation refractory period.

16 fasting cats were used to investigate the effect of acupuncture on discharge of gastric signal vagal efferent fibers (GSVEF). 1. The discharge of GSVEF may increase or decrease while artificially increasing intragastric pressure. 2. Both manual acupuncture and electronic acupuncture could enhance or decrease GSVEA's discharge. All results suggest that acupuncture may adjust gastric activity through affecting gastric vago-vagal reflex.