Safety and efficacy of peripheral blood stem cells collection in healthy children and pediatric patients with thalassemia major weighing 20 kg or less.

BACKGROUND: Peripheral blood stem cell (PBSC) collection in children poses challenges due to their small size, low body weight (BW), and unique pediatric physiology, especially among children weighing 20 kg (kg) or less. METHODS: PBSC collection data of both healthy children and patients with thalassemia major (TM) weighing 20 kg or less between January 2013 and December 2020 were reviewed. Moreover, PBSCs characteristics along with various aspects of efficiency and safety between healthy donors and patients with TM were compared. RESULTS: A total of 262 PBSC procedures were performed on 255 children. Of these, 91 procedures were carried out on 85 allogeneic healthy donors, and 171 auto-backup collections were performed on 170 patients with TM to ensure PBSC availability and prevent transplantation failure. A minimum pre-apheresis hemoglobin (HGB) level of 60 g/L was discovered to be safe and feasible in patients with TM. The median CD34+ cell dose in the PBSC product during the initial apheresis procedure was higher in healthy donors compared to patients with TM (7.29 ± 5.28 × 106 cells/kg vs5.88 ± 4.23 × 106 cells/kg, P = .043). The total CD34+ cells/kg recipient weight exhibited a positive correlation with pre-apheresis monocyte counts, but a negative correlation with donor weight. Apheresis significantly reduced hematocrit and platelet counts in the allogeneic group compared to the autologous group. Patients with TM experienced a higher occurrence of bone pain related to granulocyte colony-stimulating factor treatment. Notably, no serious complications related to PBSCs mobilization, central venous catheter placement, or the apheresis procedure were observed in either group. CONCLUSIONS: PBSCs collection was both safe and effective in healthy children and pediatric patients with TM weighing 20 kg or less.

The Effect of Iron Overload on the Mobilization of Peripheral Blood Hematopoietic Stem Cells in Pediatric Patients with Thalassemia Major.

INTRODUCTION: The purpose of this study was to examine the effect of iron overload on the mobilization of peripheral blood stem cells (PBSCs) in pediatric patients with ß-thalassemia major (TM). METHODS: We retrospectively reviewed the records of 226 patients with TM from whom PBSCs were collected. Iron overload was based on serum ferritin level, and liver and cardiac iron overload was measured by magnetic resonance imaging (MRI) T2*. RESULTS: The mean age of the TM patients was 7.35 ± 3.41 years. Of the patients, only 171 received MRI. Of the 171 patients, 35 had normal liver iron levels, 39 mild liver iron overload, 90 intermediate liver iron overload, and 7 severe liver iron overload. The intermediate + severe group was associated with significantly higher age and BMI and lower leukapheresis product white blood cell count and CD34+ cell levels (all, p < 0.05). CONCLUSION: Leukapheresis indices were similar between patients with different degrees of iron overload according to the ferritin level and cardiac iron overload, in which the later might be due to the small number of patients with cardiac overload. In patients with TM, the intermediate and severe liver iron overload was associated with poorer mobilization of PBSCs.

Transplant Outcomes in Beta-Thalassemia Major Patients Receiving Combined Granulocyte Colony-Stimulating Factor-Primed Bone Marrow and Cord Blood Graft Compared to Granulocyte Colony-Stimulating Factor-Primed Bone Marrow Alone.

BACKGROUND: Hematopoietic stem cell transplantation (HSCT) is currently the only curative treatment for thalassemia majorTM. Graft rejection (GR) and graft-versus-host disease (GVHD) are the primary obstacles to a successful outcome. METHODS: We conducted a retrospective study of HSCT in 29 children (median age at transplantation: 6 years) with Beta-thalassemia (ß-TM) after the combined infusion of granulocyte colony-stimulating factor-primed bone marrow (G-BM) and cord blood (CB) from the human leukocyte antigen (HLA)-identical sibling donors. We also compared the outcomes of the co-transplanted children with those of children with ß-TM who received G-BM alone from an HLA-identical sibling donor (n = 26). RESULTS: Compared to the G-BM transplant (G-BMT) recipients, those who received a co-transplant had a lower incidence of grade ≥II acute (17.24 vs. 30.7%, p = 0.047) and limited chronic (0 vs.15.4%, p = 0.022) GVHD as well as a lower incidence of GR (0 vs. 7.7%, p = 0.132). Neutrophil recovery time was faster in the co-transplant group (18.5 vs. 21 days, p = 0.04). All the patients were monitored until December 31, 2016; the median follow-up time was 74 months, and the 5-year thalassemia-free survival rate was 89.7% in the co-transplant group and 84.6% in the G-BMT-alone group (p = 0.590). CONCLUSIONS: A combined CB and G-BM graft from an HLA-identical sibling donor is an effective treatment option for TM in children, with less acute and chronic GVHD.

[Outcome of childhood high-risk acute lymphoblastic leukemia treated with the ALL-BFM 95 protocol].

OBJECTIVE: To evaluate the effectiveness and the practicability of the Acute Lymphoblastic Leukemia Berlin-Frankfurt-Münster 95 (ALL-BFM 95) protocol in treating childhood high-risk acute lymphoblastic leukemia (HR-ALL). METHODS: A retrospective analysis of 47 children with newly diagnosed HR-ALL between July 2003 and August 2013 was performed. These children were treated by the ALL-BFM 95 protocol. Survival was evaluated by Kaplan Meier analysis and Log-Rank test. RESULTS: Relapse-related death occurred in 12 of 47 patients (26%), and 5 of 47 patients (11%) were treatment-related mortality. Five-year probability of event-free-survival (pEFS) was 62%. Children with hematopoietic stem cell transplantation (HSCT) after chemotherapy achieved significantly better pEFS than those with chemotherapy alone (77% vs 52%; P=0.035). The patients who were only poor responders to prednisone had a better outcome (5-year pEFS 80%) than the Days 15 and 33 bone marrow M3 subgroups (5-year pEFS 60% and 0 respectively). CONCLUSIONS: ALL-BFM 95 protocol can improve the outcome of children with high-risk ALL. The major cause of death is attributed to relapse. Chemotherapy plus HSCT can produce a better outcome than chemotherapy alone. The Days 15 and 33 bone marrow M3 subgroups have a poor prognosis.

A novel conditioning regimen improves outcomes in ß-thalassemia major patients using unrelated donor peripheral blood stem cell transplantation.

We used a novel NF-08-TM transplant protocol based on intravenous busulfan, cyclophosphamide, fludarabine, and thiotepa in 82 consecutive patients with ß-thalassemia major (TM), including 52 with allogeneic peripheral blood stem cell transplantation (PBSCT) from unrelated donors (UDs) with well-matched human leukocyte antigens and 30 with hematopoietic stem cell transplantation (HSCT) from matched sibling donors (MSDs). The median age at transplantation was 6.0 years (range, 0.6-15.0 years), and the ratio of male-to-female patients was 56:26. The median follow-up time was 24 months (range, 12-39 months). The estimated 3-year overall survival and TM-free survival were 92.3% and 90.4% in the UD-PBSCT group and 90.0% and 83.3% in the MSD-HSCT group. The cumulative incidences of graft rejection and grades III-IV acute graft-versus-host disease were 1.9% and 9.6%, respectively, in the UD-PBSCT group and 6.9% and 3.6%, respectively, in the MSD-HSCT group. The cumulative incidence of transplant-related mortality was 7.7% in the UD-PBSCT group and 10.0% in the MSD-HSCT group. In conclusion, UD-PBSCTs using the well-tolerated NF-08-TM protocol show similar results to MSD-HSCTs and can be used to treat ß-thalassemia patients in the absence of MSDs.

Prophylactic first-line antibiotics reduce infectious fever and shorten hospital stay during chemotherapy-induced agranulocytosis in childhood acute myeloid leukemia.

BACKGROUND/AIMS: There exists few pediatric data on the safety and efficacy of prophylactic antibiotics during chemotherapy-induced agranulocytosis. METHODS: We prospectively studied the incidence of infection-related fever in 38 children, aged 2-16 years, with acute myeloid leukemia (AML) over 121 chemotherapy treatment cycles. A prophylactic group (n = 18) was given either vancomycin/cefepime (400 mg/m(2), q12 h/50 mg/kg, q12 h) or piperacillin/tazobactam (110 mg/kg, q12 h). Control patients (n = 20) received no preventive antibiotics. RESULTS: The prophylactic group (59 treatment cycles) experienced fever less frequently than the control group (0.4 vs. 0.9 events; p < 0.001), had a longer interval between agranulocytosis and fever (6.4 vs. 3.8 days; p = 0.007), had a shorter duration of hospitalization (21.5 vs. 28.5 days; p < 0.001), and had a lower rate of lung infection (38.8 vs. 80.0%; p < 0.001). One patient taking vancomycin experienced a skin rash and 3 patients taking piperacillin/tazobactam had diarrhea; these side effects subsided after antibiotics were discontinued. CONCLUSIONS: In children with AML, prophylactic antibiotics during the period of chemotherapy-induced agranulocytosis can effectively reduce the incidence of infectious fever and can shorten the average length of hospital stay, improving treatment success and quality of life.

The association between incarceration and housing insecurity and advanced immune age during late life.

Emerging evidence suggests that psychosocial stress ages the immune system. Accordingly, immune aging may be an important potential mechanism linking psychosocial stress to aging-related decline and disease. Incarceration and housing insecurity represent severe and complex experiences of a multitude of psychosocial stressors, including discrimination, violence, and poverty. In this study, we investigated the association between incarceration and/or housing insecurity and advanced immune age in adults aged 55 and older. Our sample was derived from the Health and Retirement Survey (HRS), with n = 7003 individuals with valid housing insecurity data and n = 7523 with valid incarceration data. From 2016 Venous Blood Study data, we assessed immune aging using a comprehensive set of immune markers including inflammatory markers (IL-6, CRP, s-TNFR1), markers of viral control (CMV IgG antibodies), and ratios of T cell phenotypes (CD8+:CD4+, CD+ Memory: Naïve, CD4+ Memory: Naïve, CD8+ Memory: Naïve ratios). We found that both incarceration and housing insecurity were strongly associated with more advanced immune aging as indicated by increased inflammation, reduced viral control, and reduction in naïve T cells relative to memory T cells. Given that those who experienced incarceration, housing insecurity, and/or are racialized minorities were less likely to be included in this study, our results likely underestimated these associations. Despite these limitations, our study provided strong evidence that experiencing incarceration and/or housing insecurity may accelerate the aging of the immune system.

Retracted: Antitumor and apoptotic effects of 5-methoxypsoralen in U87MG human glioma cells and its effect on cell cycle, autophagy and PI3K/Akt signaling pathway.

[This retracts the article DOI: 10.5114/aoms.2019.81729.].

Transcriptomics combined with metabolomics unveiled the key genes and metabolites of mycelium growth in Morchella importuna.

Morels (Morchella) are one of the most popular edible fungi in the world, especially known for their rich nutrition and delicious taste. Earlier research indicates that the production of fruiting bodies can be affected by the growth of mycelium. To investigate the molecular mechanisms underlying mycelium growth in Morchella importuna, we performed transcriptome analysis and metabolomics analysis of three growth stages of the hypha of M. importuna. As a result, 24 differentially expressed genes, such as transketolase (tktA), glucose-6-phosphate dehydrogenase (G6PDH), fructose-diphosphate aldolase (Fba), and ribose-5-phosphate isomerase (rpiA), as well as 15 differentially accumulated metabolites, including succinate and oxaloacetate, were identified and considered as the key genes and metabolites to mycelium growth in M. importuna. In addition, guanosine 3',5'-cyclic monophosphate (cGMP), guanosine-5'-monophosphate (GMP), and several small peptides were found to differentially accumulate in different growth stages. Furthermore, five pathways, namely, starch and sucrose metabolism, pentose and glucuronate interconversions, fructose and mannose metabolism, tyrosine metabolism, and purine nucleotides, enriched by most DEGs, existed in the three compared groups and were also recognized as important pathways for the development of mycelium in morels. The comprehensive transcriptomics and metabolomics data generated in our study provided valuable information for understanding the mycelium growth of M. importuna, and these data also unveiled the key genes, metabolites, and pathways involved in mycelium growth. This research provides a great theoretical basis for the stable production and breeding of morels.

The antitumor effect of mycelia extract of the medicinal macrofungus Inonotus hispidus on HeLa cells via the mitochondrial-mediated pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Inonotus hispidus (I. hispidus), known as shaggy bracket, has been used extensively in China and some East Asian countries as a traditional medicinal macrofungus to treat difficult diseases, such as diabetes, gout, and arthritis. Modern pharmacological research has shown that I. hispidus has an important application value in antitumor treatment. However, the main anti-cervical cancer activity substances from its mycelia and its mechanisms are still not clear. AIMS OF THE STUDY: To enrich the germplasm resources of I. hispidus, to reveal the antitumor activity of the extract from the mycelium of I. hispidus against cervical cancer, and to preliminarily analyze its action mechanism. MATERIALS AND METHODS: The SH3 strain was isolated from wild fruiting bodies and identified by morphology and molecular biology. The antitumor active component from the mycelium of I. hispidus was isolated and identified with liquid chromatography-tandem mass spectrometry. The cell viability was assessed by MTT assay. The cell cycle distribution, apoptotic cell detection, and mitochondrial membrane potential were detected by flow cytometer. The expression of apoptosis-related proteins was assessed by Western blotting. The inhibition of tumor growth in vivo was assessed by a mouse xenograft model. RESULTS: The SH3 strain was isolated and identified as a new strain of I. hispidus. The antitumor active component containing cyclic peptides from the mycelium of I. hispidus (CCM) was isolated for the first time. In addition, we found that CCM had a strong inhibitory effect on HeLa proliferation in vitro and in vivo. Mechanically, the CCM blocked the cell cycle at the G0/G1 phase, decreased the mitochondrial membrane potential, and eventually promoted apoptosis of HeLa cells through the mitochondria-mediated pathway by upregulating the expression levels of Bax, cytochrome C, cleaved caspase-9, and cleaved caspase-3 and downregulating the expression level of Bcl-2. CONCLUSIONS: Our study not only enriches the strain resources of I. hispidus but also confirms that the mycelium of this strain has active components that can inhibit cervical cancer. This is highly significant for the development of active drugs and drug lead molecules for treating cervical cancer.

Combined Effect of CYP2C19 Genetic Polymorphisms and C-Reactive Protein on Voriconazole Exposure and Dosing in Immunocompromised Children.

Background: Pediatric patients have significant interindividual variability in voriconazole exposure. The aim of the study was to identify factors associated with voriconazole concentrations and dose requirements to achieve therapeutic concentrations in pediatric patients. Methods: Medical records of pediatric patients were retrospectively reviewed. Covariates associated with voriconazole plasma concentrations and dose requirements were adjusted by using generalized linear mixed-effect models. Results: A total of 682 voriconazole steady-state trough concentrations from 91 Chinese pediatric patients were included. Voriconazole exposure was lower in the CYP2C19 normal metabolizer (NM) group compared with the intermediate metabolizer (IM) group and the poor metabolizer (PM) group (p = 0.0016, p < 0.0001). The median daily dose of voriconazole required to achieve therapeutic range demonstrated a significant phenotypic dose effect: 20.8 mg/kg (range, 16.2-26.8 mg/kg) for the CYP2C19 NM group, 18.2 mg/kg (range, 13.3-21.8 mg/kg) for the CYP2C19 IM group, and 15.2 mg/kg (range, 10.7-19.1 mg/kg) for the CYP2C19 PM group, respectively. The extent of impact of C-reactive protein (CRP) levels on voriconazole trough concentrations and dose requirements varied between CYP2C19 phenotypes. Increases of 20, 120, 245, and 395 mg/L from 5 mg/L in CRP levels were associated with increases in voriconazole trough concentration by 22.22, 50, 64.81, and 75% respectively, in the NM group; by 39.26, 94.48, 123.93, and 146.63%, respectively, in the IM group; and by 17.17, 37.34, 46.78, and 53.65%, respectively, in the PM group. Meanwhile, increases of 20, 120, 245, and 395 mg/L from 5 mg/L in CRP levels were associated with increases in voriconazole dose requirements by 7.15, 14.23, 17.35, and 19.43%, respectively, in the PM group; with decreases in voriconazole dose requirements by 3.71, 7.38, 8.97, and 10.03%, respectively, in the NM group; and with decreases by 4, 9.10, 11.05, and 12.35%, respectively, in the IM group. In addition, age and presence of immunosuppressants had significant effects on voriconazole exposure. Conclusions: Our study suggests that CYP2C19 phenotypes, CRP concentrations, age, and the presence of immunosuppressants were factors associated with the pharmacokinetic changes in voriconazole. There was heterogeneity in the effect of CRP on voriconazole plasma concentrations across different CYP2C19 genotypes. Combining relevant factors with dose adaptation strategies in therapeutic drug monitoring may help to reduce the incidence of subtherapeutic and supratherapeutic concentrations in clinical practice.

Encouraging the outcomes of children with beta-thalassaemia major who underwent fresh cord blood transplantation from an HLA-matched sibling donor.

BACKGROUND: Allogeneic haematopoietic stem cell transplantation (allo-HSCT) is currently the only curative treatment for thalassaemia major (TM). Cord blood (CB) from a sibling has different characteristics from marrow and has potential advantages and disadvantages as a stem cell source. METHODS: We retrospectively analyzed 68 children with beta-thalassaemia major (ß-TM) who underwent fresh cord blood transplantation (F-CBT) from an HLA-matched sibling donor (MSD) between June 2010 and July 2018 in the Department of Pediatrics, Nanfang Hospital and Haematology-Oncology, Shenzhen Children's Hospital. RESULTS: The median infused doses of total nucleated cells (TNCs) and CD34 + cells were 8.51×107/kg and 3.16×105/kg, respectively. The median time to neutrophil and platelet engraftment were, respectively, 27 and 31 days. The cumulative probabilities of acute and chronic graft-versus-host disease (GVHD) were very low after F-CBT (7.8% and 0.0%, respectively). Of the 68 paediatric patients, 67 patients survived during a median follow-up period of 61 months. The estimated 5-year probability of overall survival (OS) and disease-free survival (DFS) were 98.5% and 87.9%, respectively. Three patients experienced graft rejection (GR) (4.5%), and we identified CD34 + cell dose as a significant risk factor for graft failure (p = 0.036) in stratify analysis. CONCLUSIONS: The above results indicate that patients with ß-TM have excellent outcomes after F-CBT from an HLA-MSD.

Soil microbial diversity and functional capacity associated with the production of edible mushroom Stropharia rugosoannulata in croplands.

In recent years, a rare edible mushroom Stropharia rugosoannulata has become popular. S. rugosoannulata has the characteristics of easy cultivation, low cost, high output value, and low labor requirement, making its economic benefits significantly superior to those of other planting industries. Accumulating research demonstrates that cultivating edible fungus is advantageous for farming soil. The present experiment used idle croplands in winter for S. rugosoannulata cultivation. We explored the effects of S. rugosoannulata cultivation on soil properties and soil microbial community structure in paddy and dry fields, respectively. We cultivated S. rugosoannulata in the fields after planting chili and rice, respectively. The results showed that Chili-S. rugosoannulata and Rice-S. rugosoannulata planting patterns increased the yield, quality and amino acid content of S. rugosoannulata. By analyzing the soil properties, we found that the Chili-S. rugosoannulata and Rice-S. rugosoannulata cropping patterns increased the total nitrogen, available phosphorus, soil organic carbon, and available potassium content of the soil. We used 16s amplicons for bacteria and internal transcribed spacer (ITS) region for fungi to analyze the microbial communities in rhizosphere soils. Notably, S. rugosoannulata cultivation significantly increased the abundance of beneficial microorganisms such as Chloroflexi, Cladosporium and Mortierella and reduce the abundance of Botryotrichumin and Archaeorhizomyces. We consider S. rugosoannulata cultivation in cropland can improve soil properties, regulate the community structure of soil microorganisms, increase the expression abundance of beneficial organisms and ultimately improve the S. rugosoannulata yield and lay a good foundation for a new round of crops after this edible mushroom cultivation.

Cancer Mortality in U.S.-Born versus Foreign-Born Asian American Groups (2008-2017).

BACKGROUND: Asian Americans (AA) are the fastest growing ethnic group in the United States with high proportions of immigrants. Nativity is important as cancer risk factors vary by country. We sought to understand differences in cancer mortality among AAs by nativity (foreign-born vs. U.S.-born). METHODS: Ninety-eight thousand eight hundred and twenty-six AA (Asian Indian, Chinese, Filipino, Japanese, Korean, Vietnamese) decedents with cancer-related deaths from U.S. death certificates (2008-2017) were analyzed. Thirteen cancers that contribute significantly to Asian-American cancer mortality were selected and categorized by etiology: tobacco-related, screen-detected, diet-/obesity-related, and infection-related. Ten-year age-adjusted mortality rates [AAMR; 95% confidence interval (CI); per 100,00] and standardized mortality ratios (SMR; 95% CI) using foreign-born as the reference group were calculated. RESULTS: Overall, foreign-born AAs had higher mortality rates than U.S.-born. Japanese U.S.-born males had the highest tobacco-related mortality rates [foreign-born AAMR: 43.02 (38.72, 47.31); U.S.-born AAMR: 55.38 (53.05, 57.72)]. Screen-detected death rates were higher for foreign-born than U.S.-born, except for among Japanese males [SMR 1.28 (1.21-1.35)]. Diet-/obesity-related AAMRs were higher among females than males and highest among foreign-born females. Foreign-born males and females had higher infection-related AAMRs than U.S.-born; the highest rates were foreign-born males-Korean [AAMR 41.54 (39.54, 43.53)] and Vietnamese [AAMR 41.39 (39.68, 43.09)]. CONCLUSIONS: We observed substantial heterogeneity in mortality rates across AA groups and by nativity. Contrary to the Healthy Immigrant Effect, most foreign-born Asians were dying at higher rates than U.S.-born AAs. IMPACT: Disaggregated analysis of AA cancers, targeted and culturally tailored cancer screening, and treatments for infections among foreign-born Asians is critical for cancer prevention efforts.

Whole-genome assembly and analysis of a medicinal fungus: Inonotus hispidus.

Inonotus hispidus (I. hispidus) is a medicinal macrofungus that plays a key role in anti-tumor and antioxidant functions. To further understand and enhance the value of I. hispidus, we performed whole-genome sequencing and an analysis of its strain for the first time. I. hispidus was sequenced using the Illumina NovaSeq high-throughput sequencing platform. The genome length was 35,688,031 bp and 30 contigs, with an average length of 1,189,601.03 bp. Moreover, database alignment annotated 402 CAZyme genes and 93 functional genes involved in regulating secondary metabolites in the I. hispidus genome to find the greatest number of genes involved in terpenes in that genome, thus providing a theoretical basis for its medicinal value. Finally, the phylogenetic analysis and comparative genomic analysis of single-copy orthologous protein genes from other fungi in the same family were conducted; it was found that I. hispidus and Sanghuangporus baumii have high homology. Our results can be used to screen candidate genes for the nutritional utilization of I. hispidus and the development of high-yielding and high-quality I. hispidus via genetic means.

Features of cytomegalovirus infection and evaluation of cytomegalovirus-specific T cells therapy in children's patients following allogeneic hematopoietic stem cell transplantation: A retrospective single-center study.

Cytomegalovirus (CMV) infection remains a critical cause of mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT), despite improvement by pre-emptive antivirus treatment. CMV-specific cytotoxic T lymphocytes (CMV-CTL) are universally used and proven well-tolerance after allo-HSCT in adult clinical trials. However, it is not comprehensively evaluated in children's patients. Herein, we conducted a retrospective study to determine the risk factors of CMV infection and evaluation of CMV-CTL in children patients who underwent allo-HSCT. As result, a significantly poor 5-year overall survival was found in the CMV infection group (87.3 vs. 94.6%, p=0.01). Haploidentical HSCT (haplo-HSCT) was identified as an independent risk factor for CMV infection through both univariate and multivariate analyses (p<0.001, p=0.027, respectively). Furthermore, the cumulative incidence of CMV infection was statistically higher in the haplo-HSCT group compared to the HLA-matched donor group (44.2% vs. 21.6%, p<0.001). Finally, the overall response rate of CMV-CTL was 89.7% (26/29 patients) in CMV infection after allo-HSCT. We concluded that CMV infection following allo-HSCT correlated with increased mortality in children's patients, and haplo-HSCT was an independent risk factor for CMV infection. Adoptive CMV-CTL cell therapy was safe and effective in pediatric patients with CMV infection.

[Effect of cyclophosphamide on hematopoietic stem cells in mice with iron overload].

OBJECTIVE: To explore the effect of cyclophosphamide on hematopoietic stem cells (HSCs) in mice with iron overload. METHODS: Mouse models of iron overload were established in 30 male C57BL/6 mice by intraperitoneal injections of iron dextran at low (0.25 g/kg), moderate (0.5 g/kg), and high (1 g/kg) doses (n=10), with another 10 PBS-treated mice as the control group. The changes in body weight, liver, spleen and bone marrow of the mice were recorded, and serum level of ferritin was detected. The mice receiving a moderate dose of iron dextran were further divided into 8 groups for observation at different time points (D1, D2, D3, D4, D5, D6, D7, and D14 groups) and were given intraperitoneal injection of 50 mg/kg cyclophosphamide (Cy) for 2 consecutive days. Peripheral blood cells, bone marrow mononuclear cells (BMMNCs), and the frequencies of different HSCs (HPCs, HSCs, LT-HSCs) in the BMMNCs were monitored. The cell cycle distribution in the HSCs, level of reactive oxygen species and the microenvironment of the HSCs were analyzed using flow cytometry. RESULTS: Compared with the control mice, the mice with iron overload showed obvious weight loss with significantly increased serum ferritin level, enlargement of the liver and spleen, and iron deposition in the organs (P < 0.05). No significant changes were noted in the peripheral blood of the mice with iron overload. The cyclophosphamide-treated mice exhibited significantly decreased number of WBCs and lymphocyte ratio at days 1 to 4 (P < 0.05). The numbers of BMMNCs and HPCs in mice with iron overload did not show significant changes as compared with those in the control mice, but the numbers of HSCs and LTHSCs decreased significantly in the mice with iron overload (P < 0.05). In cyclophosphamide-treated mice, the number of HSCs increased since day 1 and reached the peak level on day 3 (P < 0.05). Compared with those in the control group, the HSCs did not exhibit significant changes in cell cycle distribution in mice with iron overload, but the proportion of G0/G1 cells decreased significantly in cyclophosphamide group since day 1 and reached the lowest level on day 3 (P < 0.05). CONCLUSIONS: Iron deposition in the bone marrow causes long- term damages of the HSCs in the bone marrow but does not induce obvious changes in the peripheral blood. In mice with iron overload, intraperitoneal injection of 50 mg/kg cyclophosphamide for two days promotes cell cycle changes of the resting HSCs to mobilize the HSCs, and this effect is the most obvious on day 4.

[Effects of water and nitrogen coupling under furrow irrigation on tree growth, absorption and utilization of water and nitrogen of Populus tomentosa]. / 沟灌水氮耦合对毛白杨林木生长及水氮吸收利用的影响.

We explored the coupling effects of water and nitrogen in furrow irrigation on the growth and absorption and utilization of water and nitrogen in young poplar trees (triploid Populus tomentosa), under three irrigation levels (W20, W33, W45; when the soil water potential of 40 cm under the ditch reaches -20, -33 and -45 kPa respectively, irrigate), four N application levels (N120, N190, N260 and N0; the fertilization amount was 120, 190, 260 and 0 kg·hm-2·a-1), and natural conditions (CK). Based on the growth status of trees, the optimal combination of irrigation level and nitrogen application rate under furrow irrigation conditions was determined. The results showed that W20N120 (high water and low fertilizer; soil water potential threshold for initiating irrigation was -20 kPa and N application rate was 120 kg·hm-2·a-1) had the strongest effect on the stand productivity, with a value of 33.37 m3·hm-2·a-1. The significant coupling effect of water and N was detected only for tree height and total individual biomass. The increase of both irrigation amount and N application rate could increase the amount of N uptake, being mainly affected by the latter. The total amount of N uptake was the highest in the W20N260 treatment and reached 112.17 kg·hm-2·a-1, being 74.0% higher than that in CK. Among all the treatments, N uptake efficiency and N fertilizer partial productivity of W20N120 were the highest and significantly higher than those of the other treatments. The N uptake efficiency of the whole plant, aboveground part, and belowground part reached 36.8%, 28.5% and 6.4% in the W20N120 treatment, and its total N partial productivity reached 221.4 kg·kg-1. The effect of irrigation amount under different water-nitrogen coupling treatments on the irrigation water use efficiency was significant. Among them, irrigation water use efficiency in W45N260 was the highest and reached 13.66 g·kg-1. W20N120 had the highest water uptake amount and efficiency, which were 13268.28 t·hm-2 and 129.4%, respectively. To achieve great benefits, adequate irrigation (-20 kPa) and relatively low N application rate (120 kg·hm-2·a-1) should be selected during the young growth of the triploid P. tomentosa.