Psychological status of the staff in a general hospital during the outbreak of coronavirus disease 2019 and its influential factors. / 2019å† çŠ¶ç— æ¯’ç— ç–«æƒ æœŸé—´æŸç»¼åˆåŒ»é™¢å‘˜å·¥çš„å¿ƒç†çŠ¶æ€åŠå ¶å½±å“å› ç´ .

OBJECTIVES: To understand the psychological status of the staff in a general hospital during the coronavirus disease 2019 and its influential factors, and to provide references for the mental health services to hospital staff. METHODS: Using star platform of questionnaire, the staff in the general hospital were investigated via Depression, Anxiety, Stress Scale (DASS-21), Social Support Rating Scale (SSRS) and Simplified Coping Style Questionnaire (SCSQ). The influential factors were discussed by descriptive analysis, rank sum test, single factor analysis, correlation analysis and multiple factors binary logistic regression analysis. RESULTS: A total of 2 060 valid questionnaires were collected. The negative emotions of nurses and cleaners were the most obvious. The depression scores, anxiety scores and stress scores for nurses and cleaners were 5.06±7.47, 6.36±7.84, 9.75±8.65, and 6.72±8.84, 4.51±6.56, 9.69±9.56, respectively. Multivariate binary logistic regression analysis showed that staff types, education levels, job status, economic situation and concerns on the supplies of protective goods were the main influential factors for depression; staff types, contacting status with infected patients, economic situation, concerns on the supplies of protective goods, history of disease were the main influential factors for anxiety; contacting status with infected patients, economic situation, concerns on the supplies of protective goods were the main influential factors for stress. CONCLUSIONS: There are differences in psychological characteristics among different groups of staff in the general hospital under the outbreak. Thus psychological protection and intervention measures should be formulated according to different groups and work status.

A Rare Morphology Resembling APL with t (11;12) (p15;q13) in Acute Myeloid Leukemia: Case Report and Literature Review.

BACKGROUND: To investigate the clinical features of and therapeutic options for a rare morphology resembling APL with t (11;12) (p15;q13) in acute myeloid leukemia. METHODS: One case of APL-like acute leukemia with a t (11;12) (p15;q13) translocation is reported and related literature is retrospectively reviewed. RESULTS: A rare acute myeloid leukemia with a t (11;12) (p15;q13) translocation was diagnosed by morphology, immunophenotyping, chromosome analysis, and fusion gene detection, without finding a classical t (15;17) (q24.1;q21.1) translocation and the PML-RARa fusion gene. The patient responded poorly to differentiation induction therapy with all-trans retinoic acid (ATRA) and arsenic trioxide (ATO). In the three previous cases re-ported, poor results were obtained with ATRA and/or ATO therapy. CONCLUSIONS: We reported a rare meaningful AML patient with t (11;12) (p15;q13). Standard AML regimens may be preferred. These APL-like leukemias may benefit from hematopoietic stem cell transplantation treatment. Further investigation involving more cases is needed to determine the role of t (11;12) (p15;q13) in AML and to find better therapy choices.

Identification of two residues within the NS1 of H7N9 influenza A virus that critically affect the protein stability and function.

The emerging avian-origin H7N9 influenza A virus, which causes mild to lethal human respiratory disease, continues to circulate in China, posing a great threat to public health. Influenza NS1 protein plays a key role in counteracting host innate immune responses, allowing the virus to efficiently replicate in the host. In this study, we compared NS1 amino acid sequences of H7N9 influenza A virus with those of other strains, and determined NS1 protein variability within the H7N9 virus and then evaluated the impact of amino acid substitutions on ability of the NS1 proteins to inhibit host innate immunity. Interestingly, the amino acid residue S212 was identified to have a profound effect on the primary function of NS1, since S212P substitution disabled H7N9 NS1 in suppressing the host RIG-I-dependent interferon response, as well as the ability to promote the virus replication. In addition, we identified another amino acid residue, I178, serving as a key site to keep NS1 protein high steady-state levels. When the isoleucine was replaced by valine at 178 site (I178V mutation), NS1 of H7N9 underwent rapid degradation through proteasome pathway. Furthermore, we observed that P212S and V178I mutation in NS1 of PR8 virus enhanced virulence and promoted the virus replication in vivo. Together, these results indicate that residues I178 and S212 within H7N9 NS1 protein are critical for stability and functioning of the NS1 protein respectively, and may contribute to the enhanced pathogenicity of H7N9 influenza virus.

The effect of TLX3 expression on the prognosis of pediatric T cell acute lymphocytic leukemia--a systematic review.

Whether TLX3 is a predictor of prognosis of pediatric T cell acute lymphocytic leukemia (T-ALL) is controversial, with some studies concluding that it is and others concluding the opposite. Therefore, a systematic review was performed to explore the relationship of TLX3 expression with the prognosis of pediatric T-ALL. The PubMed database, The Cochrane Library, conference proceedings, EMBASE databases, and references of published trials and review articles were searched. Two reviewers independently assessed the quality of the trials and extracted data. Hazard ratios (HRs) for disease-free survival (DFS) and odds ratios (OR) for 5-year DFS were pooled using the STATA package. Ultimately, six trials involving 515 patients with pediatric T-ALL were analyzed. The pooled HR (1.07 [0.32, 3.56], p = 0.91) for DFS and OR (1.30 [0.52, 3.27], p = 0.57) for 5-year DFS showed that the TLX3-positive group showed no statistically significant difference with the TLX3-negative group. Our results suggested that TLX3 expression is not an indicator for the prognosis of pediatric T-ALL.

Consolidation therapy with autologous stem cell transplantation after remission of induction chemotherapy prolongs the survival of patients with peripheral T-cell lymphoma.

Background: There was little evidence of autologous stem cell transplantation (ASCT) as consolidation therapy after remission of induction for patients with Peripheral T-cell lymphoma (PTCL). In this study, we conducted a comparative analysis of real-world survival outcomes between consolidation therapy and observation in patients with PTCL. Methods: A total of 92 patients with peripheral T-cell lymphoma (PTCL) who were admitted to the Department of Hematology, Huadong Hospital Affiliated with Fudan University from January 2013 to April 2019 were divided into two groups based on whether they were treated with high-dose therapy (HDT) followed by autologous hematopoietic stem cell transplantation (ASCT): ASCT as consolidation therapy (n=30) and observation (n=62). Clinical characteristics, treatment patterns, and survival outcomes were analyzed between the two groups. Univariate and Cox multivariate regression analyses were also performed to detect prognostic factors of survival. Results: With a median follow-up time of 41 months, the median overall survival (OS) of peripheral T-cell lymphoma patients treated with ASCT was not reached; the median progression-free survival (PFS) was 77.0 months, which was much higher than that of patients without ASCT (p<0.003 for OS, p=0.015 for PFS). Subgroup analysis found that patients with high risks benefited more from ASCT. Combination with hemophagocytic lymphohistiocytosis (HLH) (p<0.001), clinical stage more than III (p=0.014), IPI score above 3 (p=0.049), and bone marrow involvement (p=0.010) were the independent prognostic factors significantly associated with worse OS and PFS. Additionally, pegylated liposomal doxorubicin (PLD)-containing chemotherapy regimen could bring a higher overall response rate (ORR) and prolong the survival of patients with PTCL who underwent ASCT. Conclusion: ASCT may improve the long-term survival of patients with PTCL as consolidation therapy after achieving complete or partial remission of induction treatment, particularly for those with high risks. The chemotherapy regimen containing pegylated liposomal doxorubicin may induce deeper remission than traditional doxorubicin in PTCL. It is crucial to identify the specific groups most likely to benefit from upfront ASCT.

The impact of death attitudes on death education needs among medical and nursing students.

BACKGROUND: Medical and nursing students will play an essential role in delivering palliative care in the future. Death education is important in preparing them for future palliative care, however, little is known about students education needs and how death attitudes affect such needs in Mainland China. OBJECTIVES: The purpose of this survey was to investigate the death education needs of medical and nursing students and to evaluate the impact of death attitudes on death education needs. DESIGN: Multi-center, cross-sectional survey. SETTINGS: Fourteen medical and nursing colleges & universities in Hunan, Sichuan, Liaoning, Guangdong, Shandong, and Shanxi provinces in China. PARTICIPANTS: The sample included 1044 medical and nursing students from six provinces. METHODS: In this multi-center cross-sectional study, all data were collected through an online questionnaire that included demographic information and questions on death-related experiences. In addition, the Death Attitude Profile-Revised and the Death Education Needs Scale were used to evaluate students' death attitudes and death education needs , respectively. RESULTS: The students had a mean death education needs score of 38.85 ± 7.25 (range: 10-50), yet only 20.9 % of them had received palliative care-related training. Being female (B:3.869, 95 % CI:2.849-4.889), fear of death (B:0.119, 95 % CI:0.005-0.232), and neutral acceptance (B:0.787, 95 % CI:0.638-0.936) were associated with higher death education needs, while death avoidance (B: -0.226, 95 % CI: -0.368 ~ -0.083), approach acceptance (B: -0.126, 95 % CI: -0.215 ~ -0.036), and escape acceptance (B: -0.198, 95 % CI: -0.322 ~ -0.073) were associated with lower death education needs. CONCLUSIONS: The high level of death education needs and low training rate in palliative care among medical and nursing students in mainland China indicates a gap that needs to be addressed. Students' death education needs were affected by gender and death attitudes, which provides implications for the future development of palliative care training models.

Design of blueberry anthocyanin/TiO2 composite layer-based photoanode and N-doped porous blueberry-derived carbon-loaded Ni nanoparticle-based counter electrode for dye-sensitized solar cells.

P25/PBP (TiO2, anthocyanins) prepared by combining PBP (blueberry peels) with P25, and N-doped porous carbon-supported Ni nanoparticles (Ni@NPC-X) prepared using blueberry-derived carbon were used for the application as photoanode and the counter electrode, respectively, in dye-sensitized solar cells (DSSCs) to create a new perspective for blueberry-based photo-powered energy systems. PBP was introduced into the P25 photoanode and carbonized to form a C-like structure after annealing that improved its adsorption capacity for N719 dye, contributing a 17.3% higher power conversion efficiency (PCE) of P25/PBP-Pt (5.82%) than that of P25-Pt (4.96%). The structure of the porous carbon changes from a flat surface to a petal-like structure due to the N doping by melamine, and the specific surface area increases. N-doped three-dimensional porous carbon supported the loading and reduced the agglomeration of Ni nanoparticles, reducing the charge transfer resistance, and providing a fast electron transfer path. The doping of Ni and N on the porous carbon worked synergistically to enhance the electrocatalytic activity of the Ni@NPC-X electrode. The PCE of the DSSCs assembled by Ni@NPC-1.5 and P25/PBP was 4.86%. Also, the Ni@NPC-1.5 electrode exhibited 116.12 F g-1 and a capacitance retention rate of 98.2% (10 000 cycles), further confirming good electrocatalysis and cycle stability.

Effects of mindfulness decompression therapy on mental health and job burnout among nurses working in the frontline of the novel coronavirus pandemic: A retrospective study.

OBJECTIVES: As the coronavirus disease 2019 (COVID-19) pandemic continues to spread worldwide, nucleic acid detection is a key step in controlling it. Psychological issues and job burnout of nurses working in nucleic acid sampling roles for long periods have become apparent. This study aimed to explore the effects of mindfulness decompression therapy on mental health and job burnout in front-line nurses working in nucleic acid sampling during the pandemic. METHODS: Nucleic acid sampling frontline nurses who were positive for burnout on both the Symptom Checklist-90 (SCL-90) and the Maslach Burnout Inventory-General Scale (MBI-GS) were selected as the participants. Frontline nurses in the nucleic acid testing area who received routine psychological nursing intervention from June 2020 to April 2021 were used as the control group. Nurses who received both routine psychological nursing and mindfulness decompression therapy from May 2021 to December 2021 formed the "mindfulness" subject group. We compared the two groups' primary outcome measures of SCL-90 and MBI-GS scores. RESULTS: Before the intervention, there were no significant differences between the two groups in general data, SCL-90 scores, and MBI-GS scores. After the mindfulness decompression therapy, according to SCL-90 and MBI-GS scales, psychological distress and job burnout of nurses in the mindfulness group were significantly better than those in the control group. CONCLUSION: Mindfulness decompression therapy can effectively improve mental health and relieve job burnout in frontline nurses in nucleic acid sampling areas, which is worthy of clinical application. Randomized controlled trials are still needed, however, to fully confirm the effects of mindfulness decompression therapy.

Maintenance regimen of GM-CSF with rituximab and lenalidomide improves survival in high-risk B-cell lymphoma by modulating natural killer cells.

BACKGROUND: The treatment of high-risk B-cell lymphoma (BCL) remains a challenge, especially in the elderly. METHODS: A total of 83 patients (median age 65 years), who have achieved a complete response after induction therapy, were divided into two groups: R2 + GM-CSF regimen (lenalidomide, rituximab, granulocyte-macrophage colony-stimulating factor [GM-CSF]) as maintenance therapy (n = 39) and observation (n = 44). The efficacy of the R2 + GM-CSF regimen as maintenance in patient with high-risk BCL was analyzed and compared with observation. RESULTS: The number of natural killer cells in patients increased after R2 + GM-CSF regimen administration (0.131 × 109 /L vs. 0.061 × 109 /L, p = 0.0244). Patients receiving the R2 + GM-CSF regimen as maintenance therapy had longer remission (duration of response: 18.9 vs. 11.3 months, p = 0.001), and longer progression-free survival (not reached (NR) vs. 31.7 months, p = 0.037), and overall survival (OS) (NR vs. NR, p = 0.015). The R2 + GM-CSF regimen was safe and well tolerated. High international prognostic index score (p = 0.012), and high tumor burden (p = 0.005) appeared to be independent prognostic factors for worse PFS. CONCLUSIONS: The maintenance therapy of R2 + GM-CSF regimen may improve survival in high-risk BCL patients, which might be modulated by amplification of natural killer cells. The efficacy of the R2 + GM-CSF maintenance regimen has to be further validated in prospective random clinical trials.

Alleviating allergic airway diseases by means of short-term administration of IL-2 and dexamethasone.

BACKGROUND: IL-2 combined with dexamethasone can upregulate regulatory T (Treg) cells, but the mechanism is still under exploration. OBJECTIVE: Although previous studies focused on upregulating Treg cells in normal mice, here we investigated whether the IL-2 and dexamethasone combination treatment can upregulate Treg cells in pathological conditions, specifically in alleviating allergic airway disease. We also examined the potential pathway involved in Treg cell upregulation by IL-2 and dexamethasone. METHODS: We evaluated the dose of IL-2 and dexamethasone required to upregulate Treg cells in vivo and in vitro. We also tested IL-2 and dexamethasone in the intervention of allergic airway disease in a murine model. RESULTS: We found that administration of 400,000 IU of IL-2 and 0.1 mg of dexamethasone per mouse was effective in upregulating Treg cells, as well as in alleviating allergic airway disease in an established animal model, but this phenomenon disappeared after anti-CD25 antibody administration. We discovered that an in vitro low dose of IL-2 can protect Treg cells did not protect CD4(+)CD25(-) cells from dexamethasone-induced apoptosis by affecting forkhead box O3a phosphorylation through the Akt and serum and glucocorticoid-induced protein kinase pathways. CONCLUSIONS: IL-2/dexamethasone treatment can alleviate existing allergic airway diseases by upregulating Treg cells in vivo. A low dose of IL-2 (10(-9) to 10(-11) mol/L) can protect Treg cells but not CD4(+)CD25(-) cells from dexamethasone-induced apoptosis in vitro, thereby explaining a possible mechanism of increased proportion of Treg cells.

Clinical characteristics and prognostic factors of lymphoma patients initially presenting with fever of unknown origin.

BACKGROUND: Lymphoma has been identified as the most common cause of non-infectious fever of unknown origin (FUO). However, clinical characteristics and prognostic factors in lymphoma patients with FUO are lacking. METHODS: From January 1, 2013 to December 31, 2019, our center enrolled 185 patients who initially presented with FUO but were later diagnosed with lymphoma in Huadong Hospital of Fudan University. The FUO and matched non-FUO groups were compared in terms of clinical symptoms, laboratory examinations, overall survival (OS), and progression-free survival (PFS). The prognostic factors of OS and PFS in patients with FUO were assessed by Cox analyses. RESULTS: In the FUO group (180 in total), B cell non-Hodgkin's lymphoma (B-NHL) cases were 88 (48.9%), T cell non-Hodgkin's lymphoma (T-NHL) was 60 (33.3%), NK/T cell lymphoma (NK/T-CL) was 24 (13.3%), and Hodgkin's lymphoma (HL) was 8 (4.4%). During the hospitalization, the maximum body temperature of the FUO group diagnosed with B-NHL, T-NHL, or NK/T-CL was statistically higher than that of the non-FUO group (P < 0.05). The differences in OS between the FUO and non-FUO groups were significant for HL (P = 0.006), B-NHL (P = 0.007), and T-NHL (P = 0.013). In the multivariate analyses, the log10 serum ferritin was an independent risk factor for all-cause death in patients with FUO (hazard ratio, 9.578; 95% confidence interval, 1.382-66.365; P = 0.022). CONCLUSION: We found that the subtypes of lymphoma initially presenting with FUO were mostly B-NHL and T-NHL. The detection of ferritin levels during the hospital stay may help predict the long-term survival rate in patients with FUO.

18F-fluorodeoxyglucose positron emission tomography-based prediction for splenectomy in patients with suspected splenic lymphoma.

BACKGROUND: Diagnostic splenectomy is often performed on patients with suspected splenic lymphoma. However, unnecessary splenectomy entails more harm than benefit for patients. Therefore, a preliminary screening method for patients with suspected splenic lymphoma that has high sensitivity and specificity is urgently needed. METHODS: From the pathology database at Huadong and Huashan Hospital, we retrospectively identified 60 patients of suspected splenic lymphoma who underwent fluorodeoxyglucose (FDG)-positron emission tomography (PET) before receiving a splenectomy and did not show any increase in FDG uptake except in the spleen. We compared the indicators of PET-CT, such as the maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), total lesion glycolysis (TLG), and the SUVmax of 18F-FDG uptake ratios between the spleen/liver, spleen/bone marrow, and liver/bone marrow. RESULTS: No significant differences were detected in SUVmax, TLG, MTV, or the SUVmax ratio of the liver/bone marrow between the lymphoma and benign groups. However, the SUVmax ratios of the spleen/liver and spleen/bone marrow were significantly higher in the lymphoma group than in the benign group (P=0.001; P=0.001). Receiver operating characteristic (ROC) curve analysis determined a spleen/liver SUVmax ratio of >2.42 and a spleen/bone marrow SUVmax ratio of >1.45 to be the indications for requiring a diagnostic splenectomy for lymphoma. Parallel testing increased the specificity and sensitivity of the test. CONCLUSIONS: Patients whose PET-CT results are inconclusive regarding the need for splenectomy may benefit from our prediction model. Future large-scale prospective clinical trials are required to verify these findings.

Co-infection of H9N2 Influenza A Virus and Escherichia coli in a BALB/c Mouse Model Aggravates Lung Injury by Synergistic Effects.

Pathogens that cause respiratory diseases in poultry are highly diversified, and co-infections with multiple pathogens are prevalent. The H9N2 strain of avian influenza virus (AIV) and Escherichia coli (E. coli) are common poultry pathogens that limit the development of the poultry industry. This study aimed to clarify the interaction between these two pathogens and their pathogenic mechanism using a mouse model. Co-infection with H9N2 AIV and E. coli significantly increased the mortality rate of mice compared to single viral or bacterial infections. It also led to the development of more severe lung lesions compared to single viral or bacterial infections. Co-infection further causes a storm of cytokines, which aggravates the host's disease by dysregulating the JAK/STAT/SOCS and ERK1/2 pathways. Moreover, co-infection mutually benefited the virus and the bacteria by increasing their pathogen loads. Importantly, nitric oxide synthase 2 (NOS2) expression was also significantly enhanced by the co-infection. It played a key role in the rapid proliferation of E. coli in the presence of the co-infecting H9N2 virus. Therefore, our study underscores the role of NOS2 as a determinant for bacteria growth and illustrates its importance as an additional mechanism that enhances influenza virus-bacteria synergy. It further provides a scientific basis for investigating the synergistic infection mechanism between viruses and bacteria.

Survival Benefit and Efficiency of Low Dose Decitabine With CEG Regimen Compared to Decitabine Alone in the Elderly MDS - A Multicenter, Retrospective Study.

BACKGROUND: Decitabine are used in the treatment of myelodysplastic syndrome (MDS), but none trials reported overall survival improvement. METHODS: High-risk MDS and MDS transformed AML (sAML) patients (IPSS-R > 4.5, age above 60 years) in 6 medical centers of China were treated and compared a new regimen (decitabine with CEG) consisted of low dose decitabine (15 mg/m2, days 1-3), low dose etoposide (30 mg/m2, days 4,6,8,10,12), cytarabine (10 mg/m2 per day, days 4-12) and granulocyte colony-stimulating factor (G-CSF, 5ug/kg, adjusted by patients' WBC level, 12 hours prior to decitabine administration) with decitabine alone. The endpoints were death and disease progression. RESULTS: The baseline characteristics of these 2 groups were equivalent and none patients received prior chemotherapy. The treatment response rate (P= .048) and progression free survival (PFS, P = .030) all demonstrated significant improvement compared with decitabine alone. Decitabine with CEG regimen had attained a CR rate of 45.7%, a median OS of 36 (19-53) months and a median PFS of 34 (16.7-51.3) months in high-risk MDS patients, a CR rate of 40% in sAML. While decitabine alone only attained a median OS of 26 (24.5-27.5) months and a CR rate of 18.2% as well as a median progression free survival of 20 (17.6-22.4) months in MDS patients. Treatment response to CR or PR and TP53 mutation were 2 prognostic factor for OS and PFS in decitabine with CEG regimen. CONCLUSION: Decitabine with CEG regimen showed some promising advantage in elderly, high-risk MDS.

Administration of amifostine in the stage of remission induction can benefit the patients with hematological malignancy in autologous stem cell transplantation: a retrospective study.

BACKGROUND: To investigate whether the administration of amifostine in the stage of remission induction can benefit patients with hematological malignancy in autologous stem cell transplantation (ASCT). METHODS: Two historical groups of patients who received prophylactic amifostine in the stage of remission induction and ASCT (group A, n=95) or amifostine in ASCT only (group B, n=73) were included. The chemotherapy-associated side effects in peripheral blood stem cell (PBSC) mobilization, total average monocyte per kilogram in stem cells collections, hematologic toxicity and engraftment kinetics, non-hematologic toxicity, therapeutic response after ASCT were compared between the two groups. RESULTS: For PBSCs mobilization, the rate of fever in group A was significantly higher (24/95 vs. 2/73; P=0.0001), but the incidence of emesis was significantly lower (8/95 vs. 27/73; P=0.0001) compared with group B. For collected PBSCs, the average total mononuclear cells per kilogram in group A were 7.031×108/kg, while it was 4.624×108/kg in group B (P=0.0001). The median duration of neutropenia was 8.62 days in group A, which was significantly shorter than that of group B by almost 2 days (10.51 days, P=0.038). The incidence of oral mucositis was 8.4% in group A and 32% in group B (P=0.0002). No significant differences of therapeutic response were observed between the two groups. CONCLUSIONS: Prophylactic amifostine can reduce mucositis, improve monocytes collection and promote hematopoietic recovery in ASCT.

[Comparison of the Curative Efficacy of Elderly Patients with High-Risk MDS and MDS-Transformed AML between Decitabine Combined with Low-Dose CEG Regimen and Decitabine Combined with Low-Dose CAG Regimen].

OBJECTIVE: To evaluate the efficacy of decitabine combined with low-dose CEG regimen (DCEG) and decitabine combined with low-dose CAG regimen (DCAG) in the treatment of elderly patients with MDS and MDS-transformed acute myeloid leukemia (AML). METHODS: A prospective study was conducted in 7 medical centers, 45 patients with MDS (≥ 60 years old) and MDS-transformed AML from October 2016 to January 2019 were enrolled, with the median age of 68.5 years old. The risk stratification of patients was poor or very poor, according to IPSS-R score. The treament results of decitabine combined with CEG and decitabine combined with CAG were compared. RESULTS: The comparison of the two regiem showed that the DCEG regimen had advantages on total effective rate (ORR, 86.4% vs 47.8%, respectively), overall survival time (OS) (10.0 months vs 6.0 months, respectively) and progression-free survival time (PFS) (9.0 months vs 3.0 months, respectively). About 50% of MDS patients treated by DCEG regimen achieved PR or CR, with a median OS of 31 months. Multivariate analysis showed that patients with PR or CR after induction therapy and DCEG regimen had longer survival time (31months). The incidence of bone marrow suppression, infection and treatment-related mortality rate were similar between the two groups. CONCLUSION: Decitabine combined with CEG regimen could improve the survival of patients with high-risk MDS and MDS-transformed AML. The conclusion of the reaserch needs to be validated by a larger prospective randomized clinical trial.

Efficiency and Tolerability of Induction and Consolidation Therapy with Arsenic Trioxide/Bortezomib/Ascorbic Acid/Dexamethasone (ABCD) Regimen Compared to Bortezomib/Dexamethasone (BD) Regimen in Newly Diagnosed Myeloma Patients.

PURPOSE: This study was aimed at comparing the efficacy and tolerability of an arsenic trioxide/bortezomib/ascorbic acid/dexamethasone (ABCD) regimen with efficacy and tolerability of a bortezomib/dexamethasone (BD) regimen in patients with newly diagnosed myeloma. PATIENTS AND METHODS: Fifty-seven and sixty-four patients were treated with the ABCD and BD regimens, respectively. Eligible and agreeable patients received autologous hematopoietic stem cell transplantation followed by consolidation. RESULTS: The response rates (above VGPR) were 74.1% and 32.8% in the ABCD- and BD-treated groups, respectively (P = 0.000). Compared to BD regimen, ABCD regimen significantly improved PFS (P = 0.026) and OS (P = 0.000) in newly diagnosed patients. Patients with a high tumor burden, low or standard risk, and without auto-HSCT seemed to especially benefit compared to the same group with BD regimen. ABCD also showed better tolerability with lower bone marrow suppression (P = 0.026). Furthermore, complete response or near CR after induction therapy was a good prognostic factor for ABCD-associated OS and PFS. CONCLUSION: ABCD is an effective and tolerable regimen compared with BD regimen in newly diagnosed myeloma patients. ABCD regimen could be an economical, effective, and tolerable choice in low- and standard-risk patients.

A glucocorticoid amplifies IL-2-induced selective expansion of CD4(+)CD25(+)FOXP3(+) regulatory T cells in vivo and suppresses graft-versus-host disease after allogeneic lymphocyte transplantation.

Regulatory T (Treg) cells are a subpopulation of T cells that not only prevent autoimmunity, but also control a wide range of T cell-dependent immune responses. Glucocorticoid treatment (dexamethasone, or Dex) has been reported to amplify IL-2-mediated selective in vivo expansion of Treg cells. We simultaneously administered Dex and IL-2 to the donor in a murine allogeneic lymphocyte transplantation model to expand functional suppressive CD4(+)CD25(+)FOXP3(+) T cells in the graft and to raise the regulatory T cell/effector T cell (Treg/ Teff ) ratio to prevent graft-versus-host disease (GVHD). After combined treatment of the donor with Dex (5 mg/kg/day) and IL-2 (300,000 IU/mouse/day) for 3 days, grafts were subjected to flow cytometric analysis, and transplantation was carried out from male C57BL/6 mice to female BALB/c mice aged 8-12 weeks. Results showed that short-term simultaneous administration of Dex and IL-2 markedly expanded functional suppressive CD4(+)CD25(+)FOXP3(+) T cells in the murine spleen. In this murine allogeneic transplantation model, the grafts from donors with Dex and IL-2 pre-treatment led to a longer survival time for the recipients than for the control group (median survival time > 60 day vs. 12 day, P=0.0002). The ratio of Treg/Teff also increased remarkably (0.43+/-0.15 vs. 0.14+/-0.01, P=0.01). This study demonstrated that co-stimulation with Dex and IL-2 selectively expanded functional CD4(+)CD25(+)FOXP3(+) T cells in vivo, and that grafts from donors pre-treated with Dex and IL-2 led to longer survival time and greater suppression of GVHD after allogeneic transplantation. Thus, GVHD can be suppressed by the specific expansion of regulatory T cells with Dex and IL-2 in graft donors.

Akt2 mediates glucocorticoid resistance in lymphoid malignancies through FoxO3a/Bim axis and serves as a direct target for resistance reversal.

Glucocorticoids (GCs) are widely used drugs in the treatment of lymphoid malignancies; resistance of GCs in lymphocytes confers poor prognosis and the mechanisms are poorly understood. Here, we found T-acute lymphoblastic leukemia (T-ALL) cells acquire resistance to dexamethasone (DEX)-mediated killing through abnormal activation of Akt, resulting in inhibition of the FoxO3a/Bim pathway. The resistant state was reported to be associated with increased glycolysis, NOTCH1 activating mutations and activated PI3K/ serum GS regulated kinases (SGK) pathway. Use of aforementioned pathway inhibitors blocked FoxO3a-phosphorylation and partially improved DEX-mediated killing of GC-resistant T-ALL cells, further revealing the essential role of the FoxO3a/Bim pathway in the development of GC resistance. Inhibition of Akt is most effective at restoring sensitivity to DEX of GC-resistant lymphocytes in vitro and in vivo, but shows significant hepatotoxicity in vivo. A significantly elevated expression of Akt2 not Akt1 in intrinsically, secondarily GC-resistant lymphocytes and relapsed/refractory ALL patients implicates a more specific target for GC resistance. Mechanistically, Akt2 has a stronger binding capacity with FoxO3a compared to Akt1, and acts as a direct and major negative regulator of FoxO3a activity driving GC resistance. Pharmacologic inhibition of Akt2 more effectively restores sensitivity to GCs than inhibition of Akt1 in vitro, shows higher synergistic effect acting with DEX, and reverses GC resistance in GC-resistant T- or B- lymphoid tumors in vivo with reduced liver toxicity. In summary, these results suggest that Akt2 might serve as a more direct and specific kinase mediating GC resistance through FoxO3a/Bim signaling pathway, and Akt2 inhibition may be explored as a promising target for treating GC-resistant hematopoietic malignancies.