Transformation from acute promyelocytic leukemia in pregnancy to acute myeloid leukemia with MLL-AF9 fusion gene: A case report and literature review.

RATIONALE: Because there are few evidence-based guidelines and an extremely low incidence rate, managing and treating patients who have transitioned from acute promyelocytic leukemia (APL), which was diagnosed during pregnancy, to acute myeloid leukemia (AML), can be difficult. PATIENT CONCERNS: In this case, a 34-year-old pregnant patient was diagnosed with APL in medium-risk group in June 2017. After the all-trans retinoic acid and arsenic trioxide-based full-course treatment, the patients achieved complete remission (CR) and were well-tolerated. After 5 years, the patient complained of fatigue for 3 months. DIAGNOSIS: Bone marrow examination revealed hypercellularity with approximately 50% immunophenotypic abnormal myeloblasts with MLL-AF9 fusion gene. Based on the AML diagnosis criteria of the World Health Organization, the patient was eventually diagnosed with a rare transformation from APL to AML. INTERVENTIONS: The patient was treated with two cycles of induction chemotherapy and an allogeneic hematopoietic stem cell transplantation (allo-HSCT). OUTCOMES: Until now, the patient is in continuous remission with no signs of APL and AML. LESSIONS: Despite the rarity of APL to AML transformation, it is crucial to track the disease's progress and administer treatment on time. It remains uncertain whether the risk stratification and clinical outcomes of secondary AML with MLL-AF9 are equivalent to those of de novo AML with MLL-AF9. The management and treatment of these patients should be personalized and require further observation.

Implementation of Remote Activity Sensing to Support a Rehabilitation Aftercare Program: Observational Mixed Methods Study With Patients and Health Care Professionals.

BACKGROUND: Physical activity is central to maintaining the quality of life for patients with complex chronic conditions and is thus at the core of neurorehabilitation. However, maintaining activity improvements in daily life is challenging. The novel Stay With It program aims to promote physical activity after neurorehabilitation by cultivating self-monitoring skills and habits. OBJECTIVE: We examined the implementation of the Stay With It program at the Valens Rehabilitation Centre in Switzerland using the normalization process theory framework, focusing on 3 research aims. We aimed to examine the challenges and facilitators of program implementation from the perspectives of patients and health care professionals. We aimed to evaluate the potential of activity sensors to support program implementation and patient acceptance. Finally, we aimed to evaluate patients' engagement in physical activity after rehabilitation, patients' self-reported achievement of home activity goals, and factors influencing physical activity. METHODS: Patients were enrolled if they had a disease that was either chronic or at risk for chronicity and participated in the Stay With It program. Patients were assessed at baseline, the end of rehabilitation, and a 3-month follow-up. The health care professionals designated to deliver the program were surveyed before and after program implementation. We used a mixed methods approach combining standardized questionnaires, activity-sensing data (patients only), and free-text questions. RESULTS: This study included 23 patients and 13 health care professionals. The diverse needs of patients and organizational hurdles were major challenges to program implementation. Patients' intrinsic motivation and health care professionals' commitment to refining the program emerged as key facilitators. Both groups recognized the value of activity sensors in supporting program implementation and sustainability. Although patients appreciated the sensor's ability to monitor, motivate, and quantify activity, health care professionals saw the sensor as a motivational tool but expressed concerns about technical difficulties and potential inaccuracies. Physical activity levels after patients returned home varied considerably, both within and between individuals. The self-reported achievement of activity goals at home also varied, in part because of vague definitions. Common barriers to maintaining activity at home were declining health and fatigue often resulting from heat and pain. At the 3-month follow-up, 35% (8/23) of the patients withdrew from the study, with most citing deteriorating physical health as the reason and that monitoring and discussing their low activity would negatively affect their mental health. CONCLUSIONS: Integrating aftercare programs like Stay With It into routine care is vital for maintaining physical activity postrehabilitation. Although activity trackers show promise in promoting motivation through monitoring, they may lead to frustration during health declines. Their acceptability may also be influenced by an individual's health status, habits, and technical skills. Our study highlights the importance of considering health care professionals' perspectives when integrating new interventions into routine care.

Salidroside affects the Th17/Treg cell balance in aplastic anemia via the STAT3/HIF-1α/RORγt pathway.

BACKGROUND: Acquired aplastic anemia (AA) is a life-threatening disease associated with an imbalance in Th17/Treg cells. Regulating this balance may be an effective treatment approach for AA. Rhodiola rosea has shown efficacy in AA treatment, but its mechanisms remain unclear. PURPOSE: We investigated salidroside's effect (a component of Rhodiola rosea) on Th17/Treg balance in adult AA patients and a mouse model. METHODS: HIF-1α mRNA and protein levels were measured in AA patients' peripheral blood. Flow cytometry, qRT-PCR, and WB analyzed salidroside's impact on T cell differentiation, Th17 cells, Treg cells, STAT3, HIF-1α, and RORγt expression. ELISA measured hematopoietic growth factors in mouse serum. RESULTS: AA patients exhibited elevated HIF-1α levels. Salidroside improved hematopoietic function, increasing blood cell count and enhancing bone marrow. Salidroside induced SCF, TPO, and IL-3 expression while inhibiting IL-2 in mice. Salidroside reduced STAT3, HIF-1α, RORγt, and IL-17a, while increasing FoxP3 expression, correcting the Th17/Treg imbalance in vitro and in vivo. CONCLUSION: Salidroside has potential as a novel AA treatment by correcting the Th17/Treg imbalance through the STAT3/HIF-1α/RORγt pathway.

A novel HDAC inhibitor chidamide combined with imatinib synergistically targets tyrosine kinase inhibitor resistant chronic myeloid leukemia cells.

Chidamide is a novel selective histone deacetylase inhibitor (HDACi) with promising activity in hematological malignancies, but its role in chronic myeloid leukemia (CML) was marginally addressed. In this study, we firstly demonstrated that chidamide alone inhibited CML cells proliferation, induced apoptosis and cell cycle arrest. Further, chidamide combined with imatinib (IM) induced synergistic lethality in CML cell line KBM5, as well as IM-resistant CML cells KBM5T315I, associated with a marked reduction of Bcr-Abl kinase activity and acetyl-histone H3 expression. The combination treatment markedly inhibited constitutive activity of ß-catenin signaling in IM-resistant cells and abolished the protective effects of mesenchymal stromal cells (MSCs) to CML cells. In addition, the co-treatment significantly reduced Bcr-Abl and ß-catenin transcript levels and induced apoptosis of primary CD34+ stem/progenitor cells derived from blast crisis (BC)-CML patients, but exhibited minimal toxicity to normal CD34+ progenitors. Collectively, our data show that combination of chidamide and imatinib synergistically targets tyrosine kinase inhibitor (TKI) -resistant BC-CML cells via inhibition of Bcr-Abl and ß-catenin signaling, suggesting that this combination has the potential for treating TKI-resistant CML and improving clinical outcomes of BC-CML patients.

MicroRNA-153-3p enhances the sensitivity of chronic myeloid leukemia cells to imatinib by inhibiting B-cell lymphoma-2-mediated autophagy.

Chronic myeloid leukemia (CML) is a hematopoietic stem cell disease caused by abnormal DNA replication of bone marrow stem cells and chemotherapy resistance is a major obstacle to the effective treatment of patients with CML. Imatinib (IM), a tyrosine kinase inhibitor (TKI), is a first-line drug clinically used for CML. Mounting evidence has indicated that the dysregulation of microRNAs (miRNAs) is associated with the chemoresistance of CML. In this study, miR-153-3p, which had been implicated with numerous types of tumors, was identified to be downregulated in IM-resistant CML cells. Upregulation of miR-153-3p significantly increased IM sensitivity and decreased the survival rate of IM-resistant CML cells, whereas downregulation of miR-153-3p attenuated these effects in IM-resistant CML cells. Upregulated miR-153-3p could decrease the autophagy caused by IM in IM-resistant CML cells. Dual-luciferase reporter assays confirmed that Bcl-2 is a direct target of miR-153-3p. Bcl-2 restoration reversed the increased sensitivity to IM induced by miR-153-3p-mimic transfection in IM-resistant CML cells. The results of the present study showed that dysregulated miR-153-3p may target Bcl-2 to promote the development of IM resistance and attenuate IM-induced apoptosis in CML. Therefore, miR-153-3p upregulation combined with IM treatment may serve as a promising therapeutic strategy for patients with low sensitivity.

Inhibition of Siah2 Ubiquitin Ligase by Vitamin K3 Attenuates Chronic Myeloid Leukemia Chemo-Resistance in Hypoxic Microenvironment.

BACKGROUND A hypoxic microenvironment is associated with resistance to tyrosine kinase inhibitors (TKIs) and a poor prognosis in chronic myeloid leukemia (CML). The E3 ubiquitin ligase Siah2 plays a vital role in the regulation of hypoxia response, as well as in leukemogenesis. However, the role of Siah2 in CML resistance is unclear, and it is unknown whether vitaminK3 (a Siah2 inhibitor) can improve the chemo-sensitivity of CML cells in a hypoxic microenvironment. MATERIAL AND METHODS The expression of Siah2 was detected in CML patients (CML-CP and CML-BC), K562 cells, and K562-imatinib-resistant cells (K562-R cells). We measured the expression of PHD3, HIF-1α, and VEGF in both cell lines under normoxia and hypoxic conditions, and the degree of leukemic sensitivity to imatinib and VitaminK3 were evaluated. RESULTS Siah2 was overexpressed in CML-BC patients (n=9) as compared to CML-CP patients (n=13). Similarly, K562-imatinib-resistant cells (K562-R cells) showed a significantly higher expression of Siah2 as compared to K562 cells in a hypoxic microenvironment. Compared to normoxia, under hypoxic conditions, both cell lines had lower PHD3, higher HIF-1α, and higher VEGF expression. Additionally, Vitamin K3 (an inhibitor of Siah2) reversed these changes and promoted a higher degree of leukemic sensitivity to imatinib. CONCLUSIONS Our findings indicate that the Siah2-PHD3- HIF-1α-VEGF axis is an important hypoxic signaling pathway in a leukemic microenvironment. An inhibitor of Siah2, combined with TKIs, might be a promising therapy for relapsing and refractory CML patients.

[Establishing the Ion Torrent PGM Sequencing Methods for the Clinical Diagnosis of MPN Patients].

OBJECTIVE: To investigate the feasibility and relibility of rapidly and accurately acquiring the informations of gene mutations in MPN patients by using self-designed custom MPN mutation-related multipe-PCR primer kit and next generation Ion Torrent PGM sequencing platform. METHODS: The bone marrow samples of 10 MPN patients with JAK2V617F and/or CALR+, Ph- confirmed by sanger sequencing method were collected and were re-detected by using next generation Ion Torrent PGM sequencing method, then the consistence of results of above-mentioned 2 kinds of detection methods was compared. RESULTS: In terms of JAK2V617F, MPL and CALR mutations, the results of Ion Torrent PGM sequencing were complete consistent with results of Sanger sequencing, except 52 bp deletion of CALR gene, which conld not be detected by next generation Ion Torrent PGM sequencing method in all bone marrow samples. CONCLUSION: The detection of multiple gene mutations in MPN patients by Ion Torrent PGM sequencing platform is feasible and can meet the needs of clinical testing. This method can complete detection of all 23 mutetions within 1-2 days, moreover, possesses advantages of high sensitivity, specificity, rapidity, high throughput and low cost.

Therapeutic immune monitoring of CD4+CD25+ T cells in chronic myeloid leukemia patients treated with tyrosine kinase inhibitors.

Tyrosine kinase inhibitors (TKIs), including imatinib, dasatinib and nilotinib, are effective forms of therapy for various types of solid cancers and Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia. A number of TKIs have been known to have strong effects on T cells, particularly cluster of differentiation (CD) 4+CD25+ T cells, also known as regulatory T cells (Tregs). There is currently a deficit in the available clinical data regarding this area of study. In the present study, a total of 108 peripheral blood samples were collected from patients with chronic myeloid leukemia (CML) at diagnosis (n=31), and at 3 and 6 months following treatment with TKI [imatinib (n=12), dasatinib (n=11) and nilotinib groups (n=8)] and healthy controls (n=15). Peripheral blood mononuclear cells were collected from the patients prior to and following TKI treatment. The subtype and number of T lymphocytes in patients and healthy donors were analyzed using flow cytometry. Additionally, flow cytometry and ELISA were used to detect the proliferation and suppression of Tregs. Expression of cytokines and other molecules [forkhead box P3 (FOXP3), glucocorticoid-induced tumor necrosis factor receptor (GITR) and cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4)] were also analyzed at 3 and 6 months following treatment with TKIs. It was indicated that, at diagnosis, a similar number of lymphocytes were detected in patients and control. However, following treatment with a TKI, the number of total T cells, Tregs, CD4+ T and CD8+ T cells decreased to various degrees in patients. Furthermore, the decrease in the number of Tregs was more significant with time. Although treatment with imatinib, dasatinib and nilotinib demonstrated similar inhibitory effects on the quantity of Tregs in vivo, the TKIs exhibited differential effects on the function of Tregs in vitro. Proliferation, suppression and expression of cytokines [interleukin (IL)-4, IL-10 and transforming growth factor (TGF)-ß] and molecules (FOXP3, GITR and CTLA-4) decreased significantly in treatment groups with imatinib and dasatinib. The decrease was not significant in the nilotinib treatment group. Imatinib and dasatinib may exert more marked inhibitory roles compared with nilotinib on regulating the number and function of Tregs. These results suggest that personalized treatment and follow-up of CML patients during TKI treatment, particularly for those who received post-transplant TKI treatment may be beneficial.

Inhibition of autophagy enhances the selective anti-cancer activity of tigecycline to overcome drug resistance in the treatment of chronic myeloid leukemia.

BACKGROUND: Drug resistance and disease progression are still the major obstacles in the treatment of chronic myeloid leukemia (CML). Increasing researches have demonstrated that autophagy becomes activated when cancer cells are subjected to chemotherapy, which is involved in the development of drug resistance. Therefore, combining chemotherapy with inhibition of autophagy serves as a new strategy in cancer treatment. Tigecycline is an antibiotic that has received attention as an anti-cancer agent due to its inhibitory effect on mitochondrial translation. However, whether combination of tigecycline with inhibition of autophagy could overcome drug resistance in CML remains unclear. METHODS: We analyzed the biological and metabolic effect of tigecycline on CML primary cells and cell lines to investigate whether tigecycline could regulate autophagy in CML cells and whether coupling autophagy inhibition with treatment using tigecycline could affect the viabilities of drug-sensitive and drug-resistant CML cells. RESULTS: Tigecycline inhibited the viabilities of CML primary cells and cell lines, including those that were drug-resistant. This occurred via the inhibition of mitochondrial biogenesis and the perturbation of cell metabolism, which resulted in apoptosis. Moreover, tigecycline induced autophagy by downregulating the PI3K-AKT-mTOR pathway. Additionally, combining tigecycline use with autophagy inhibition further promoted the anti-leukemic activity of tigecycline. We also observed that the anti-leukemic effect of tigecycline is selective. This is because the drug targeted leukemic cells but not normal cells, which is because of the differences in the mitochondrial biogenesis and metabolic characterization between the two cell types. CONCLUSIONS: Combining tigecycline use with autophagy inhibition is a promising approach for overcoming drug resistance in CML treatment.

TNF-α enhances vascular cell adhesion molecule-1 expression in human bone marrow mesenchymal stem cells via the NF-κB, ERK and JNK signaling pathways.

The migration of circulating mesenchymal stem cells (MSCs) to injured tissue is an important step in tissue regeneration and requires adhesion to the microvascular endothelium. The current study investigated the underlying mechanism of MSC adhesion to endothelial cells during inflammation. In in vitro MSC culture, tumor necrosis factor­α (TNF­α) increased the level of vascular cell adhesion molecule­1 (VCAM­1) expression in a dose­dependent manner. The nuclear factor-κB (NF-κB), extracellular signal­regulated kinase (ERK) and c­Jun N­terminal kinase (JNK) signaling pathway inhibitors, pyrrolidine dithiocarbamate (PDTC), U0126 and SP600125, respectively, suppressed VCAM­1 expression induced by TNF­α at the mRNA and protein levels (P<0.05). TNF­α augmented the activation of NF­κB, ERK and JNK, and promoted MSC adhesion to human umbilical vein endothelial cells; however, the inhibitors of NF­κB, ERK and JNK did not affect this process in these cells. The results of the current study indicate that adhesion of circulating MSCs to the endothelium is regulated by TNF-α-induced VCAM-1 expression, which is potentially mediated by the NF­κB, ERK and JNK signaling pathways.

Immunomodulatory effects of mesenchymal stromal cells-derived exosome.

The mechanisms underlying immunomodulatory ability of mesenchymal stromal cells (MSCs) remain unknown. Recently, studies suggested that the immunomodulatory activity of MSCs is largely mediated by paracrine factors. Among which, exosome is considered to play a major role in the communication between MSCs and target tissue. The aim of our study is to investigate the effect of MSCs-derived exosome on peripheral blood mononuclear cells (PBMCs), especially T cells. We find that the MSCs-derived exosome extracted from healthy donors' bone marrow suppressed the secretion of pro-inflammatory factor TNF-α and IL-1ß, but increased the concentration of anti-inflammatory factor TGF-ß during in vitro culture. In addition, exosome may induce conversion of T helper type 1 (Th1) into T helper type 2 (Th2) cells and reduced potential of T cells to differentiate into interleukin 17-producing effector T cells (Th17). Moreover, the level of regulatory T cells (Treg) and cytotoxic T lymphocyte-associated protein 4 were also increased. These results suggested that MSC-derived exosome possesses the immunomodulatory properties. However, it showed no effects on the proliferation of PBMCs or CD3+ T cells, but increases the apoptosis of them. In addition, indoleamine 2, 3-dioxygenase (IDO) was previously shown to mediate the immunoregulation of MSCs, which was increased in PBMCs co-cultured with MSCs. In our study, IDO showed no significant changes in PBMCs exposed to MSCs-derived exosome. We conclude that exosome and MSCs might differ in their immune-modulating activities and mechanisms.

Correlation between deletion of the CDKN2 gene and tyrosine kinase inhibitor resistance in adult Philadelphia chromosome-positive acute lymphoblastic leukemia.

BACKGROUND: Frequency relapses are common in Philadelphia chromosome-positive (Ph-positive) acute lymphoblastic leukemia (ALL) following tyrosine kinase inhibitors (TKIs). CDKN2A/B is believed to contribute to this chemotherapy resistance. METHODS: To further investigate the association between CDKN2 status and TKI resistance, the prevalence of CDKN2 deletions and its correlation with a variety of clinical features was assessed in 135 Ph-positive ALL patients using interphase fluorescence in situ hybridization (I-FISH). RESULTS: Results showed that no difference occurred between patients with CDKN2 deletion (44/135) and wild-type patients in sex, age, and complete remission (CR) rate following induction chemotherapy combined with tyrosine kinase inhibitors (TKIs). However, CDKN2 deletion carriers demonstrated higher white blood cell (WBC) count, enhanced rates of hepatosplenomegaly (P = 0.006), and upregulation of CD20 expression (P = 0.001). Moreover, deletions of CDKN2 resulted in lower rates of complete molecular response (undetectable BCR/ABL), increased cumulative incidence of relapse, short overall survival (OS), and disease-free survival (DFS) time (P < 0.05) even though these patients received chemotherapy plus TKIs followed by allogenic hematopoietic stem cell transplantation (Allo-HSCT). In the case of 44 patients who presented with CDKN2 deletion, 18 patients were treated with dasatinib treatment, and another 26 patients were treated with imatinib therapy, and our study found that there were no differences associated with OS (P = 0.508) and DFS (P = 0.555) between the two groups. CONCLUSIONS: CDKN2 deletion is frequently acquired during Ph-positive ALL progression and serves as a poor prognostic marker of long-term outcome in Ph-positive ALL patients with CDKN2 deletion even after the second-generation tyrosine kinase inhibitor treatment.

CDKN2 Gene Deletion as Poor Prognosis Predictor Involved in the Progression of Adult B-Lineage Acute Lymphoblastic Leukemia Patients.

Deletion of cyclin-dependent kinase inhibitor 2A/B (CDKN2A/B) is well known in many hematologic malignancies, but only few reports have investigated this deletion effect on clinical prognosis. This study performed analysis of the CDKN2 deletion in 215 adult B- lineage acute lymphoblastic leukemia (B-ALL) patients, and related cytogenetic prognostic factors (BCR/ABL; E2A/PBXl; TEL/AML1; Mixed Lineage Leukemia (MLL) rearrangement; MYC, Immunoglobulin heavy locus (IGH) translocation). The prevalence of CDKN2 deletions in all study populations was 28.4%. There is no difference between patients with CDKN2 deletion and wild-type patients in sex, age, white blood cells (WBC) count, BM blast percentage, extra infiltration and induction complete remission (CR) rate. Analysis in relapse patients revealed that the distribution of CDKN2 deletion is higher in relapse patients (44.6%) than all patients (28.4%, P=0.006). Deletion of CDKN2 was significantly associated with poor outcomes including decreased overall survival (OS) (P<0.001), lower disease free-survival (DFS) (P<0.001), and increased cumulative incidence of relapse (P=0.002); Also, CDKN2 deletion was strongly associated with IGH translocation (P=0.021); and had an adverse effect on patients with BCR-ABL fusion gene or with MLL rearrangement. Patients with CDKN2 gene deletion benefited from allogenic hematopoietic stem cell transplantation (Allo-HSCT). Deletion of CDKN2 gene was commonly observed through leukemia progression and was poor prognostic marker in long-term outcomes.

Prognostic Significance of Monosomal Karyotype in Adult Patients With Acute Myeloid Leukemia Treated With Risk-Adapted Protocols.

BACKGROUND: The monosomal karyotype (MK) is a well-known adverse prognostic factor and has been found to be related to poor outcome in patients with acute myeloid leukemia (AML). However, the outcome in MK-positive AML patients undergoing different therapies has not been well investigated. PATIENTS AND METHODS: We retrospectively analyzed clinical and laboratory features in 225 MK-positive AML patients. Clinical outcome of overall survival (OS) and disease-free survival (DFS) was evaluated in patients according to age group and in patients who received different therapy protocols. RESULTS: The proportion of MK-positive patients increased along with age. Also, patients who were treated with high-dose cytarabine (HD-Ara-C) as consolidation therapy followed by allogeneic hematopoietic stem cell transplantation (allo-HSCT) demonstrated longer OS and DFS compared to allo-HSCT or HD-Ara-C alone. Patients treated with allo-HSCT alone exhibited longer DFS compared to patients treated with HD-Ara-C alone. No difference in OS was discovered between these 2 single protocols. CONCLUSION: MK was associated with a lower complete remission rate. HD-Ara-C therapy followed by allo-HSCT could improve the prognosis of MK-positive AML patients.

TNF-α -308 G>A polymorphism and risk of bone marrow failure syndrome: A meta-analysis.

The influence of the TNF-α -308 G>A polymorphism on bone marrow failure syndrome susceptibility is unclear. We have conducted a meta-analysis of all relevant published studies. We searched PubMed, Chinese Biomedical Literature and China National Knowledge Infrastructure databases up to February 2015. Odds ratios (ORs) with 95% confidence intervals (CIs) were applied to assess the strength of associations. Eleven case-control studies with a total sample size of 909 cases and 1803 controls were eligible to assess the association between the TNF-α -308 G>A polymorphism and susceptibility to bone marrow failure syndrome. Overall, the TNF-α -308 G>A polymorphism was significantly associated with an increased risk of bone marrow failure syndrome in any genetic model. In stratified analysis by disease type, there was a significant association between the TNF-α -308 G>A polymorphism and increased risk of aplastic anemia but no significant association with myelodysplastic syndrome (AA vs. GG: OR=2.23, 95% CI=1.23-4.05, P=0.006; recessive model: OR=3.52, 95% CI=1.30-9.53, P=0.010). In subgroup analysis by ethnicity, there were significant associations between the TNF-α -308 G>A polymorphism and increased risk of bone marrow failure syndrome for Caucasians in two models, but not in Asian populations (AA vs. GG: OR=2.66, 95% CI=1.36-5.21, P=0.003; recessive model: OR=2.68, 95% CI=1.37-5.24, P=0.002). In conclusion, our meta-analysis suggests that the TNF-α -308 G>A polymorphism may contribute to the risk of bone marrow failure syndrome, particularly among Caucasian and aplastic anemia patients. Further investigations are needed to clarify the role of the TNF-α -308 G>A polymorphism in bone marrow failure syndrome.

Risk-factor analysis of poor graft function after allogeneic hematopoietic stem cell transplantation.

The objective of this study was to investigate the main risk factors for poor graft function (PGF) after allogeneic hematopoietic stem cell transplantation (allo-HSCT), to allow the improvement of transplantation outcomes through preventive measures. Clinical data for 124 patients who received allo-HSCT were analyzed retrospectively. There were 83 males (66.9%) and 41 females (33.1%) with a median age of 28 years (4-60 years). The median follow-up time was 7 months (1-116 months). Factors analyzed included age, gender, disease diagnosis, source of hematopoietic stem cells, donor type, human leukocyte antigen (HLA) matching, conditioning regimen, numbers of infused mononuclear cells and CD34(+) cells, donor-recipient sex and blood-type matching, prophylactic treatment of graft-versus-host disease (GVHD), grades of GVHD, Epstein-Barr virus or cytomegalovirus (CMV) infection, post-transplantation lymphoproliferative disorders and hepatic veno-occlusive disease. Data were analyzed by univariate and multivariate conditional logistic regression analyses. Among the 124 patients who underwent allo-HSCT, 15 developed PGF (12.1%). Univariate logistic regression analysis identified age, donor-recipient blood type and CMV infection (in 30 days) as potential risk factors for PGF. Multivariate analysis of factors with P<0.1 in univariate analysis showed that age, donor-recipient blood type and CMV infection (in 30 days) were significant risk factors for PGF. Patients were divided into subgroups based on age <20, 20-30, 30-40, and >40 years. The risk of PGF increased 2.747-fold (odds ratio (OR)=2.625, 95% confidence interval: 1.411-5.347) for each increment in age level. Patients with mismatched blood type (OR=4.051) or CMV infection (OR=9.146) had an increased risk of PGF. We conclude that age, donor-recipient blood-type matching and CMV infection are major risk factors for PGF after allo-HSCT.

[TNF-α stimulates bone marrow mesenchymal stem cell VCAM-1 production by ERK signaling pathway].

This study was aimed to explore the effect of TNF-α on the vascular cell adhesion molecule 1 (VCAM-1) expression of human bone marrow mesenchymal stem cells (BMMSC) and the relationship between this process and ERK signalling pathway. BMMSC were isolated by density gradient centrifugation combined with adherent culture method, and then identified by surface antigen expression and differentiation potential. Flow cytometry was used to detect expression of VCAM-1 on BMMSC exposed to TNF-α at different concentrations, and the effect of ERK inhibitor U0126 on VCAM-1 of BMMSC. ERK signaling pathway activation was analyzed by Western blot. The results showed that BMMSC positively expressed CD29, CD69, CD44, CD105, and negatively expressed CD34, CD45. BMMSC could be induced to differentiate into osteoblasts and adipocytes. Flow cytometry analysis showed that after the TNF-α stimulation, the expression of VCAM-1 on BMMSC increased in a dose-dependent manner. And this increase was inhibited by U0126. TNF-α caused activation of ERK signal pathway, and U0126 suppressed this effect induced by TNF-α. It is concluded that TNF-α can increase expression of VCAM-1 of BMMSC via ERK signaling pathway.

[Dynamic of phytoplankton abundance and the relationship with environmental factors in Dianshan Lake, Shanghai].

During January 2004 to December 2006, the abundance of phytoplankton and environmental factors such as the water temperature, wind speed, transparency of water (SD), TN, TP, pH, and permanganate index were monitored monthly in Dianshan Lake. The water quality of Dianshan Lake was in the mid-eutrophication state. The correlation analysis between phytoplankton community and environmental factors were performed. It indicated that the phytoplankton abundance, cyanobacteria abundance in Dianshan Lake were positively correlated with temperature (r = 0.487, r = 0.497), pH (r = 0.415, r = 0.379) and permanganate index (r = 0.460, r = 0.436), and negatively correlated with SD (r = -0.382, r = -0.394). Chlorophyta abundance in Dianshan Lake was positively correlated with PO4(3-) -P (r = 0.466). There was also a significant positive correlation between phytoplankton abundance and cyanobacteria abundance (r = 0.970). According to (CCA) ordination analysis, temperature, DO, SD and PO4(3-) -P were main factors affecting dynamic characteristics of phytoplankton community. The meteorological and hydrological factors were more important than nutrition concentration related to the water bloom in Dianshan Lake.