Refractory hepatosplenic T-cell lymphoma was successfully treated with salvage allogeneic hematopoietic stem cell transplantation combined with enhanced myeloablative preconditioning.

This study aims to evaluate the clinical benefit of salvage allogeneic hematopoietic stem cell transplantation (allo-HSCT) in combination with enhanced myeloablative preconditioning in the treatment of refractory liver and spleen T-cell lymphomas. A retrospective analysis was performed on three patients (with refractory liver and spleen T-cell lymphomas) who have been treated with salvage allo-HSCT combined with enhanced myeloablative preconditioning. One of three patients had a liver biopsy; the other two underwent bone marrow analysis using morphology, immunology, cytogenetics, and molecular biology. All three patients were resistant to chemotherapy and with a high tumor load, so a new total body irradiation/splenic region irradiation/GEM/CLAG/ATG preconditioning regimen was conducted and followed with salvage HSCT. Two patients received haploidentical-donor hematopoietic stem cell transplants, and one received an unrelated full-donor hematopoietic stem cell transplant. The three patients survived disease-free until May 2021. Clinically, hepatosplenic T-cell lymphoma (HSTCL) is rare, with a poor prognosis and chemotherapy response. Based on the present study's encouraging clinical results, salvage allo-HSCT in conjunction with an enhanced myeloablative preconditioning regiment may be an effective and safe treatment for HSTCL.

Multicenter study of combination DEP regimen as a salvage therapy for adult refractory hemophagocytic lymphohistiocytosis.

Hemophagocytic lymphohistiocytosis (HLH) is a refractory immune disorder with a significant risk of death. Although standard therapy has dramatically improved survival in HLH patients, approximately 30%, especially adults, show no response to current treatment strategies. This prospective study aimed to investigate the efficacy of liposomal doxorubicin treatment combined with etoposide and methylprednisolone (doxorubicin-etoposide-methylprednisolone; DEP) as a salvage therapy for adult refractory HLH. Adult patients who did not achieve at least partial response 2 weeks after initial standard HLH therapy were enrolled in this study between June 2013 and June 2014. Response to salvage therapy was assessed at 2 and 4 weeks after initiation of DEP therapy and patients were followed until death or until November 2014. Sixty-three refractory HLH patients were enrolled, including 29 cases of lymphoma-associated HLH, 22 cases of Epstein-Barr virus-associated HLH, and 4 cases of familial HLH. There were 8 cases with unknown underlying diseases. Seventeen cases (27.0%) achieved complete response and 31 cases (49.2%) achieved partial response. The overall response was 76.2% (48/63). Patients who showed no response to DEP died within 4 weeks after salvage therapy. Twenty-nine of the 48 patients who achieved partial or complete response survived to subsequent chemotherapy, allogenic hematopoietic stem cell transplantation, or splenectomy. Our study suggests that DEP regimen is an effective salvage regimen for adult refractory HLH, which can prolong patient survival as we continue to understand the responsible mechanisms and bridge the gap between HLH and its underlying diseases. This study was registered in the Chinese Clinical Trials Registry Platform (http://www.chictr.org.cn/) as ChiCTR-IPC-14005514.

[Clinical analyses of 80 hemophagocytic lymphohistiocytosis patients with Epstein-Barr viremia].

OBJECTIVE: To analyze the clinical characteristics, treatment and prognosis of hemophagocytic lymphohistiocytosis (HLH) patients with Epstein-Barr viremia (EBV). METHODS: A retrospective study was conducted to analyze the clinical data of 80 HLH patients aged ≥ 14 years with EBV-DNA >1 000 copies/ml in peripheral blood from 2008 to 2013. RESULTS: There were EBV-HLH (n = 46), HLH-associated lymphoma (n = 30) and primary HLH (n = 4). Among the relevant laboratory parameters, inter-group statistical differences existed only in alanine transaminase (ALT) and aspartate aminotransferase (AST) (P = 0.021, 0.035). The median follow-up period was 2.0 (0.5-20.0) months. And the 1-month, 3-month, 6-month and 12-month overall survival rates were 58.8%, 37.5%, 29.7% and 19.6% respectively. CONCLUSIONS: HLH patients with EBV have a pernicious clinical course with a poor prognosis. And it makes little sense for distinguishing HLH-associated lymphoma from EBV-HLH through routine laboratory tests.

Severe graft-versus-host disease post allogeneic hematopoietic stem cell transplantation due to loss of HLA heterozygosity in recipient lymphocytes after full graft rejection.

Germ cell tumors complicated by hematological malignancy (HM) are a rare clinical phenomenon. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potentially effective therapy, but graft-versus-host disease (GVHD) is a life-threatening complication. We report a case of a 13-year-old female patient diagnosed with germ cell tumors followed by acute lymphoblastic leukemia. After chemotherapy, she received allo-HSCT and her chimerism rate decreased rapidly to near zero by 6 months without evidence of HM recurrence. However, she developed severe, multiorgan GVHD-like manifestations. DNA analysis revealed the pathogenesis of GVHD to be loss of HLA heterozygosity in recipient hematopoietic cells.

The effects of copper ions and copper nanomaterials on the output of amino acids from marine microalgae.

In this study, the marine microalgae Skeletonema costatum and Nitzschia closterium were exposed to different forms of copper, such as a metal salt (Cu2+), a nano-metal (nano-Cu), and nano-metal oxide (nano-CuO). During a 96-h exposure to nanoparticles (NPs) and salt, the cell number, Cu2+ concentration in the culture medium, morphology, and intracellular amino acids were measured to assess the toxicity of the copper materials and the toxicity mechanism of the NPs. As results, the toxicity of Cu2+, nano-Cu, and nano-CuO to marine phytoplankton decreased in order. The EC50 values of Cu2+ and nano-Cu for S. costatum and N. closterium ranged from 0.356 to 0.991 mg/L and 0.663 to 2.455 mg/L, respectively. Nano-Cu inhibits the growth of marine phytoplankton by releasing Cu2+; however, nano-CuO is harmful to microalgae because of the effect of NPs. The secretion of extracellular polymeric substances by microalgae could also affect the toxicity of nano-Cu and nano-CuO to microalgae. S. costatum was more sensitive to copper than N. closterium. Cu2+, nano-Cu, and nano-CuO all reduced per-cell amino acids and the total output of algae-derived amino acids by affecting the growth of the phytoplankton. This study helps to understand the risk assessment of nano-Cu and nano-CuO to marine microalgae.

Alone and combined toxicity of ZnO nanoparticles and graphene quantum dots on microalgae Gymnodinium.

Investigation of ZnO nanoparticles (nano-ZnO) and graphene quantum dots (GQDs) toxicology on dinoflagellate Gymnodinium helps to understand the effects of different surface characteristic nanoparticles on marine algae. The growth and biological responses of the algae exposed to 1, 10, 20 mg L-1 nano-ZnO and GQDs in f/2 media were explored. Nano-ZnO showed slight effects on algal cells growth, while the growth inhibition rates of Gymnodinium increased as GQDs concentration increasing. Both nanoparticle treatments induced accumulation of reactive oxygen species and activated intracellular antioxidant defensive system, including SOD and ATPase, which were related to the two nanoparticles concentration. Under combined exposure of nano-ZnO and GQDs, the inhibitory effects decreased compared to the single GQDs and showed antagonistic effect. The addition of nano-ZnO could decrease the toxicity of GQDs due to aggregation and sedimentation interaction between nanoparticles. The morphologic change of the cells observed by SEM proved that nanoparticles adsorbed onto the cell surfaces and caused the cell shrinkage.

Coaching to develop leadership for healthcare managers: a mixed-method systematic review protocol.

BACKGROUND: An increasing number of interventions have focused on leadership development for healthcare managers, among which coaching is a common strategy. The purpose of the present systematic review is to synthesize evidence on the effect of coaching in developing leadership of healthcare managers. METHODS AND ANALYSIS: A literature search will be conducted in six English databases (MEDLINE (Ovid), CINAHL, Embase, Cochrane library, Nursing & Allied Health Premium, and Scopus) and four Chinese databases (Wanfang, CNKI, SinoMed, and VIP) from inception to April 1st, 2022. The titles, abstracts, and full texts of the studies will be screened by two independent researchers to determine their eligibility. The RoB 2, ROBINS-I, CASP, and MMAT will be applied to assess the quality of randomized trials, non-randomized studies, qualitative studies, and mixed-method studies, respectively. We will then extract the study characteristics, participant characteristics, and study outcomes of the reviewed papers. The Aims, Ingredients, Mechanism, and Delivery framework will be used to extract the components of coaching strategies. For quantitative data, a meta-analysis will be performed if sufficient data are available; otherwise, we will conduct a narrative synthesis. Thematic synthesis methods will be used for qualitative data analysis. DISCUSSION: By conducting this systematic review, we expect to synthesize evidence regarding the components of coaching for leadership development among healthcare managers; the influence of coaching on leadership development among managers at the individual, unit-wide, or organizational level; and how managers view coaching as a leadership development strategy. TRIAL REGISTRATION: PROSPERO registration number: CRD42020194290 .

The allelopathy and underlying mechanism of Skeletonema costatum on Karenia mikimotoi integrating transcriptomics profiling.

The roles of allelopathy for succession of marine phytoplankton communities remain controversial, especially for the development of blooms. Physiological parameters measurement (Fv/Fm value, MDA content, SOD activity, Na+/K+, Ca2+/ Mg2+-ATPase activity, cell size, chlorophyll content, apoptosis and cell cycle) and whole transcriptome profiling analysis were used to investigate allelopathy effect of Skeletonema costatum on Karenia mikimotoi. Filtrate and extracts from S. costatum culture inhibited the growth of K. mikimotoi. Allelopathic effects were dose-dependent for filtrate culture and extract culture. K. mikimotoi scavenged excessive ROS and adapted to the stress fastly and easily, so oxidative damage was not the main cause of the growth inhibition. Allelochemicals of S. costatum were found to influence the structure and function of cell membrane of K. mikimotoi by damaging membrane structure till to cell necrosis, which caused high mortality. Coupled with the sensitivity of algal cells to environmental stress and restricted cell cycle, allelopathy was suggested to be deeply detrimental to the development of competition algal population.

Two cases of acute lymphoid leukemia patients with loss of heterozygosity in HLA region before transplantation.

Leukemia is a complex disease in which mutations and other genomic and epigenomic abnormalities play a role in both its initiation and progression. Acute lymphoid leukemia (ALL) patients with loss of heterozygosity (LOH) in the HLA region before transplantation have been described rarely. In this report, we described two ALL cases with LOH encompassing the HLA, wholly or partly. HLA molecular typing was performed on peripheral blood (PB) and somatic cell. Simultaneously, we performed whole-exome sequencing. Typing results on PB samples collected during blast crisis demonstrated complete or partial homozygosity at the -A, -B, -C, -DR, and -DQ loci. Two somatic samples demonstrated heterozygosity at all loci. LOH at the HLA gene locus may significantly influence the donor search, resulting in misidentification of homozygous donors. We recommend confirming the patients' HLA typing with hematological malignancies when homozygosity is detected at any locus by using somatic samples or alternatively from PB when remission is achieved.

Galectin-9 and PSMB8 overexpression predict unfavorable prognosis in patients with AML.

Acute myeloid leukemia (AML) is a deadly heterogeneous hematologic malignancy. Despite the well-characterized genetic characteristics and new promising targeted therapies for AML, the clinical outcome remains suboptimal. Galectin-9 (Gal-9) is a good potential target due to its immunosuppressive capacity in inflammatory processes. In our study, we firstly performed a wide range of integrated bioinformatical approach to assess the importance of Gal-9 by analyzing the expression, potential function and prognostic impact in AML. The results indicated that Gal-9 is overexpressed in AML cells, especially when relapse after hematopoietic stem cell transplantation (HSCT) and predicts poor prognosis. Co-expression analysis showed Gal-9 has a strong positive correlation with proteasome subunit beta type-8 (PSMB8), which was also highly expressed in AML with poor prognosis, implying a synergy in cell survival, cell signaling and the development of AML. In summary, we have confirmed the overexpression of Gal-9 and its partner PSMB8 in AML and validated their importance as prognostic factors. We propose that Gal-9 and PSMB8 could be a promising molecular target for treatment of AML and may provide more combined treatment options, especially in patients with relapse after HSCT.

The effects and mechanisms of polystyrene and polymethyl methacrylate with different sizes and concentrations on Gymnodinium aeruginosum.

In this study, Gymnodinium aeruginosum was exposed to polystyrene (PS) and polymethyl methacrylate (PMMA) of three particle sizes (0.1 µm, 1.0 µm and 100 µm) and two concentrations (10 mg/L and 75 mg/L) for 96 h. The density of algae cells, the endpoints that reactive oxygen species (ROS), total protein (TP), malondialdehyde (MDA), superoxide dismutase (SOD) and catalase (CAT), scanning and transmission electron microscopy (SEM and TEM) were used to explore the toxicity mechanism to the microalgae. At a concentration of 75 mg/L, the 96 h inhibition ratios (IR) with particle sizes of 0.1 µm, 1.0 µm and 100 µm on G. aeruginosum were 55.9%, 63.7% and 6.0% for PS, respectively, and 3.0%, 4.1% and -0.6% for PMMA, respectively. The most significant changes in ROS, TP, MDA, SOD and CAT were observed at 75 mg/L 1.0 µm of PS when treated for 96 h. When exposed to nanoplastics (NPs) and microplastics (MPs), the algae cells were damaged, and the antioxidant system was activated. Extracellular polymeric substance (EPS) could help to detoxify the algae. In general, PS was more toxic than PMMA. The toxicity of small MNPs (0.1 µm and 1.0 µm) was related to the concentrations, while large MNPs (100 µm) did not.

Size-dependent oxidative stress effect of nano/micro-scaled polystyrene on Karenia mikimotoi.

The effects of polystyrene (PS) of different sizes of diameter (65 nm, 100 nm and 1 µm) with different treat concentrations (control, 1 mg L-1 and 10 mg L-1) on growth and oxidative stress for K. mikimotoi were assessed across PS short-term exposures (3 d) and long-term exposures (13 d). The endpoints of physiological parameters such as cell density, antioxidant enzyme activity of SOD and CAT, the content of MDA and ROS level were monitored. The results showed that the CAT activity, SOD activity, MDA content and the relative ROS level reached to 377 U mgprot-1, 164 U mgprot-1, 157 nmol mgprot-1 and 10.8% when treated with 10 mg L-1 PS of 65 nm diameter; the CAT activity, SOD activity and MDA content in single K. mikimotoi reached to 0.46 U mgprot-1, 0.36 U mgprot-1 and 0.16 nmol mgprot-1 under 10 mg L-1 PS of 65 nm diameter on the third day. The relative ROS level in single K. mikimotoi was 71% under 10 mg L-1 PS of 100 nm diameter on the 13th day. The works found that the size of nano/micro-PS was a key factor that cannot be ignored. Smaller size had more serious negative effects on the growth, oxidative stress and cell microstructure. The potential cytotoxicity mechanisms were that monodisperse nanoscaled PS crossed the biological barriers and the agglomerate nanoparticles caused physical blockage, while microscaled PS may not have such an equally strong negative effects. Visualized SEM images also proved that exposing to nano/micro-PS of varies diameters led to apparent size-dependent effects. The arms race of systematic oxidative defensive and offensive between K. mikimotoi and nano/micro-PS would have considerable value in deliberating the relationship between nano/microplastics and marine phytoplankton.

Hyperthermia and Temperature-Sensitive Nanomaterials for Spatiotemporal Drug Delivery to Solid Tumors.

Nanotechnology has great capability in formulation, reduction of side effects, and enhancing pharmacokinetics of chemotherapeutics by designing stable or long circulating nano-carriers. However, effective drug delivery at the cellular level by means of such carriers is still unsatisfactory. One promising approach is using spatiotemporal drug release by means of nanoparticles with the capacity for content release triggered by internal or external stimuli. Among different stimuli, interests for application of external heat, hyperthermia, is growing. Advanced technology, ease of application and most importantly high level of control over applied heat, and as a result triggered release, and the adjuvant effect of hyperthermia in enhancing therapeutic response of chemotherapeutics, i.e., thermochemotherapy, make hyperthermia a great stimulus for triggered drug release. Therefore, a variety of temperature sensitive nano-carriers, lipid or/and polymeric based, have been fabricated and studied. Importantly, in order to achieve an efficient therapeutic outcome, and taking the advantages of thermochemotherapy into consideration, release characteristics from nano-carriers should fit with applicable clinical thermal setting. Here we introduce and discuss the application of the three most studied temperature sensitive nanoparticles with emphasis on release behavior and its importance regarding applicability and therapeutic potentials.

The interactions between micro polyvinyl chloride (mPVC) and marine dinoflagellate Karenia mikimotoi: The inhibition of growth, chlorophyll and photosynthetic efficiency.

Microplastics pose a great threat to entire marine ecosystems, but little is known about their impacts on phytoplankton, especially for the harmful dinoflagellates. In this study, effects of micro polyvinyl chloride (mPVC) on the growth, chlorophyll content and photosynthetic efficiency of the dinoflagellate Karenia mikimotoi at different periods (0, 24, 48, 72 and 96 h) were assessed using gradient concentrations (0, 5, 25, 50 and 100 mg L-1) of mPVC with a size of 1 µm. PVC microplastics had dose-dependent adverse effects on K. mikimotoi growth, chlorophyll content and photosynthetic efficiency. The density of algal cell decreased with increasing mPVC concentrations and the highest inhibitory rate (IR) was 45.8% at 24 h under 100 mg L-1 of mPVC. The total chlorophyll content and chlorophyll content in a single algal cell decreased at 96 h and the ФPSⅡ and Fv/Fm decreased 25.3% and 17.1%, respectively. The SEM images provided an intuitive visual method to observe the behaviors and interactions between microplastics and microalgae. It was found from the SEM images that microalgae was wrapped by microplastic beads. The physical blockage and aggregation were also responsible for the cytotoxicity of K. mikimotoi. Our study clarified that PVC microplastics can reduce algal growth, chlorophyll content and photosynthetic efficiency, and it is beneficial to evaluate the possible impact of plastics on aquatic ecosystems.

Separation of acrylonitrile-butadiene-styrene and polystyrene waste plastics after surface modification using potassium ferrate by froth flotation.

This work develops a simple and practical process for separation of acrylonitrile-butadienestyrene (ABS) and polystyrene (PS) waste plastics by froth flotation after surface modification using potassium ferrate. ABS plastics containing brominated flame retardants (BFRs) can release hazardous emissions during the process of disposal. Moreover, ABS and PS are typical styrene plastics with similar properties, posing severe restrictions on their separation for recycling. Thus, potassium ferrate modification was investigated and found to decrease selectively the floatability of ABS, providing available process for separation of ABS and PS. Contact angle measurements, FT-IR, XPS and SEM characterization analysis confirmed that potassium ferrate modification can induce the desired changes in the surface properties of ABS. With consideration to separation of ABS and PS, the optimum conditions are potassium ferrate concentration 0.15 M/L, modification time 15 min, temperature 60 °C, stirring rate 200 rpm, frother concentration 14.50 mg/L and flotation time 2 min. Under optimum conditions, separation of ABS and PS with different mixing ratios was accomplished with a recovery and purity of 98.60% and 98.62% respectively. Moreover, reusing of potassium ferrate solution is feasible, further eliminating emissions and cost of this process. Consequently, surface modification using potassium ferrate can be applied for facilitating flotation separation of ABS and PS waste plastics.

Inhibition of Bevacizumab-induced Epithelial-Mesenchymal Transition by BATF2 Overexpression Involves the Suppression of Wnt/ß-Catenin Signaling in Glioblastoma Cells.

BACKGROUND/AIM: Bevacizumab (BV) has been used for the treatment of recurrent glioblastoma. However, it also induces epithelial-mesenchymal transition (EMT) in glioblastoma cells, which compromises its efficacy. BATF2 (basic leucine zipper ATF-like transcription factor 2), a multi-target transcriptional repressor, has been found to suppress cancer development partly through inhibition of Wnt/ß-catenin singling. The roles of BATF2 and Wnt/ß-catenin signaling in BV-induced EMT in glioblastoma cells were investigated in this study. MATERIALS AND METHODS: BV was used to treat U87MG cells, and TOP/FOP FLASH luciferase reporters were employed to determine the activity of Wnt/ß-catenin signaling. EMT markers were detected with quantitative reverse transcription-PCR and western blotting. Immunofluorescence (IF) was used to determine the compartmentation of ß-catenin. Wound-healing, TransWell and ECIS assays were used to analyze cell adhesion, invasion and migration. RESULTS: BV induced EMT phenotype in U87MG cells, and BATF2 overexpression significantly inhibited BV-induced EMT with suppression of Wnt/ß-catenin signaling. CONCLUSION: Our findings expanded the understanding of the role of BATF2 in tumors, and also suggested a potential of using BATF2 as a therapeutic target to hinder bevacizumab induced EMT in glioblastoma.

Discovery of a Regulatory Motif for Human Satellite DNA Transcription in Response to BATF2 Overexpression.

BACKGROUND: One of the basic leucine zipper transcription factors, BATF2, has been found to suppress cancer growth and migration. However, little is known about the genes downstream of BATF2. MATERIALS AND METHODS: HeLa cells were stably transfected with BATF2, then chromatin immunoprecipitation-sequencing was employed to identify the DNA motifs responsive to BATF2. RESULTS: Comprehensive bioinformatics analyses indicated that the most significant motif discovered as TTCCATT[CT]GATTCCATTC[AG]AT was primarily distributed among the chromosome centromere regions and mostly within human type II satellite DNA. Such motifs were able to prime the transcription of type II satellite DNA in a directional and asymmetrical manner. Consistently, satellite II transcription was up-regulated in BATF2-overexpressing cells. CONCLUSION: The present study provides insight into understanding the role of BATF2 in tumours and the importance of satellite DNA in the maintenance of genomic stability.