Construction of a rapid depression screening model for blood donors in Guangzhou based on decision tree / 中国输血杂志

【Objective】 To investigate the prevalence of depression in blood donors and analyze the related factors, so as to develop a rapid depression screening model for blood donors. 【Methods】 A total of 13 015 street whole blood donors in Guangzhou Blood Center during May to August, 2020 filled in an anonymous e-questionnaire, including social demography information and the Patient Health Questionnaire-9 before donation. The cut-off value for detecting depression was 10. Logistic regression by SPSS 26.0 was used to analyze depression related factors. 2-level decision tree with 30/10 as the minimum number of cases in parent/child node, 10-fold cross validation was used to cut items of PHQ-9 to form the depression screening model. 【Results】 364 out of 13 015 (2.80%) street whole blood donors reported a score ≥ 10. Donors with 18-29 years old (P <0.05), unmarried (P<0.05), less than 50 000 RMB household income per year (P< 0.05) were more prone to depression. 81.96% donors in "<10 scores" group, while 3.85%donors in "≥ 10 scores" group were in two terminal nodes formed by Item-6, 2 and 4 of PHQ-9. After verification by the 10 fold crossover method, the estimated misclassification risk of the model was 1.7%. 【Conclusion】 The screening prevalence of depression based on PHQ-9 in Guangzhou blood donors was 2.8%(95% CI: 2.52%-3.09%) . Donation frequency was not related to depression. A rapid and efficient depression screening model for blood donors based on item-6, 2 and 4 of PHQ-9 was developed.

Using informational questionnaires to turn blood donors into hematopoietic stem cell voluntary donors: a randomized controlled trial / 中国输血杂志

【Objective】 To explore effective ways to mobilize more blood donors to become voluntary donors of hematopoietic stem cells (HSCs), so as to increase the HSCs supply in China. 【Methods】 Two scales(the information scale and the control scale) with the same items were designed and both included questions concerning the knowledge of HSCs donation and the level of demand. The information scale indicated the correct answer to these questions, while the control scale did not. A total of 3 000 blood donors in Guangzhou were randomly assigned into the intervention group (n=1 500, filled in the information scale) and the control group (n=1 500, filled in the control scale). 【Results】 Blood donors who filled in the informational scale expressed a higher intention to become HSCs volunteers (MInformation =4.32, SD=0.87; MControl=4.02, SD=0.93, t(529)=3.87, P<0.001). Altruism and perceived need (the degree of HSCs demands) were the moderators of grouping and intention, that is, the information scale made blood donors, with stronger altruism and higher perceived need, more willing to become stem cell volunteers. Perceived risk (the negative impact of HSCs donation on health) was a partial mediator of grouping and intention. The information scale reduced blood donors' anxiety about the risk of HSCs donation, and promoted their intention to become HSCs volunteers. 【Conclusion】 This study proved that the informational scale can effectively mobilize blood donors to become HSCs volunteers.

Changes of serum iron and ferritin in regular voluntary blood donors / 中国输血杂志

【Objective】 To study the effect of regular blood donation on the serum iron (SI) and serum ferritin (SF) of regular blood donors. 【Methods】 A total of 240 blood samples (4~5 mL per person, with EDTA-2K anticoagulant) from regular voluntary blood donors in our center from January to June 2019 were randomly selected as the study group. Another 200 healthy subjects without blood donation history were randomly selected as the control group. SI was measured by Ferene method, SF by chemiluminescence method, and blood routine indexes by automatic hematology analyzer. 【Results】 The Hb, RBC count, HCT and other blood routine indexes of the study group and the control group were all in the normal range. SI (mol/L) in the study gourp and the control group was 17.13±4.36 vs 17.82±5.78(P>0.05), and SF (ng/mL) was 98.34±52.74 vs 147.52±91.52 (P<0.05). 【Conclusion】 SI and SF may decrease due to regular blood donation, which deserve close follow-up to ensure the safety of regular blood donors.

Effects on the recruitment of inactive and lapsing blood donors, Questionnaire study based on motivators and deterrents / 中国输血杂志

【Objective】 To explore the effect of questionnaires on the re-recruitment of lapsed blood donors, and to ensure the retention of regular blood donors for blood supply in blood stations. 【Methods】 Blood Donation Motivation Questionnaire and Blood Donation Deterrents Questionnaire were designed for inactive and lapsing blood donors to inquire the motivation of the latest blood donation, such as "blood donation can save lives" and the reasons for no longer participating in blood donation, such as "there are no blood donation sites nearby", respectively. 13 093 blood donors with donation frequency ≥3 times and last donation during January 1 to May 17, 2018 in Guangzhou were selected as subjects. Text messages containing the links to the correspondent electronic questionnaires were sent to intervention group 1 (n=4 364) to fulfill the Blood Donation Motivation Questionnaire and intervention group 2 (n=4364) to fulfill Blood Donation Deterrents Questionnaire from May 18 to 25, 2020. None questionnaire was issued to the control group (n=4 365). The re-donation rates in the three groups within 2 months after the questionnaire delivery were analyzed by intention to treat (ITT) analysis and average treatment effect (ATT) estimation. 【Results】 The response rate of valid questionnaires was 5.422% (710/13 093), of which 7.424% (324/4 364) were in intervention group 1 and 8.845% (386/4 364) in intervention group 2. The collected questionnaire showed that the score of "blood donation can save lives" was the highest (2.31±0.79)in intervention group 1, and the score of "no blood donation site nearby" was the highest (2.31±0.80). in intervention group 2.2 months of observation showed that the re-donation rate was similar among all three groups by ITT analysis (Ps>0.05). ATT estimation results showed that the re-donation rates of intervention group 1 and intervention group 2 were 5.56%(18/324) and 3.11%(12/386), respectively(P<0.05). 【Conclusion】 Motivation questionnaire is a simple and convenient way to remind blood donors who have multiple donations to donate blood again.

The impact of ceasing mutual blood donation on voluntary blood donation in Guangzhou / 中国输血杂志

【Objective】 To investigate the impact of ceasing mutual blood donation on voluntary blood donation in Guangzhou. 【Methods】 The data of blood donation from July 2016 to December 2019 (42-month before and after the official cease of mutual blood donation) in the Blood Collection and Supply System of Guangzhou Blood Center, including whole blood donations and apheresis platelets donations, were collected for interrupted time series analysis by month. Blood donors who donated (either whole blood or platelets) during 2016 were followed up until December 31, 2019, and the re-donation rate was analyzed by Chi-square test, t test and logistic regression analysis. 【Results】 The results showed that ceasing mutual blood donation had a significantly positive effect on the increase of platelet donations, but had no significant effect on whole blood donation. In 2016, whole blood donations and platelet donations were mainly voluntary (86.4% and 60.8%, respectively). In comparison of voluntary blood donation, the overall blood deferral rate(by dual assays) of mutual blood donation was higher (P<0.01), but the difference diminished as they donated twice or more. The re-donation rate of blood donors (mutual non-remunerated, voluntary, or both) all increased after the ceasing of mutual blood donation (mutual non-remunerated, : 4.7% vs 4.0%, χ2=29.8, P<0.01; voluntary: 24.8% vs 9.9%, χ2=17295.3, P<0.01; both: 36.3% vs 28.1%, χ2=29.3, P<0.01). The re-donation rate of mutual platelet donors decreased after the ceasing of mutual blood donation, but the number of voluntary platelet donors increased. 【Conclusion】 The ceasing of mutual blood donation was in favour of voluntary blood donation in Guangzhou since various means had been previously adopted by Guangzhou Blood Center to create a long-term mechanism of voluntary blood donation. The number of voluntary blood donors has increased, and the clinical use of blood has been further guaranteed.

Clinical effect of methimazole combined with levothyroxine in the treatment of Graves disease / 中国基层医药

Objective:To explore the efficacy and safety of methimazole combined with levothyroxine in the treatment of patients with Graves disease (GD), and provide theoretical basis for clinical practice.Methods:Sixty-eight patients with confirmed GD who admitted to the 903rd Hospital of PLA from January 2013 to January 2018 were selected and divided into control group and observation group by random number table method.The control group was given propylthiouracil combined with levothyroxine.The observation group was treated with methimazole and levothyroxine.The clinical features of hyperthyroidism, changes in hormone levels, and bone metabolism were compared between the two groups before and after treatment.Results:After treatment, the incidence of exophthalmos, goiter and thyrotropin receptor antibody (TRAb) positive rate were significantly reduced in the two groups (the control group changed from 10 cases to 2 cases, and the observation group changed from 10 cases to 0 case), the differences were statistically significant (χ 2=27.1, 16.2, all P<0.05). The differences in TSH, FT 3, and FT 4 before and after treatment were statistically significant [the control group: TSH changed from (0.02±0.02)mU/L to (3.01±0.94)mU/L, FT 3 from (16.92±2.25)pmol/L to (10.29±1.68)pmol/L, FT 4 from (52.61±10.22)pmol/L to (19.82±4.11)pmol/L; the observation group: TSH from (0.02±0.01)mU/L to (1.97±1.27)mU/L, FT 3 from (17.09±2.72)pmol/L to (3.95±0.84)pmol/L, and FT 4 from (53.82±10.11)pmol/L to (12.65±3.31)pmol/L], and the improvement of TSH, FT 3 and FT 4 in the observation group were better than those in the control group ( t=3.24, 9.51, 16.31, all P<0.05). After treatment, the levels of PTH, CT, blood calcium, blood phosphorus were increased [the control group: PTH changed from (38.32±11.41)ng/L to (42.83±14.22)ng/L, CT changed from (8.66±2.22)ng/mL to (8.01±4.55)ng/mL, blood calcium level changed from (2.01±0.12)pmol/L to (2.53±0.20)pmol/L, blood phosphorus level changed from (1.12±0.08)pmol/L to (1.37±0.09)pmol/L; the observation group: PTH changed from (38.31±12.52)ng/L to (46.33±15.03)ng/L, CT changed from (8.45±2.21)ng/mL to (11.49±7.33)ng/mL, the calcium level changed from (2.02±0.98)pmol/L to (2.82±0.87)pmol/L, the blood phosphorus level changed from (1.10±0.07)pmol/L to (1.42±0.16)pmol/L]. The improvement of PTH and CT in the observation group was better than those in the control group ( t=6.51, 7.31, all P<0.05). Conclusion:Methimazole combined with levothyroxine in the treatment of GD has good therapeutic effect on the clinical characteristics of hyperthyroidism, changes in hormone levels, and bone metabolism.The clinical efficacy is reliable and there are few adverse reactions, which deserves clinical reference.

Comparison of different monitoring methods of minimal residual disease in acute lymphoblastic leukemia / 白血病·淋巴瘤

The level of minimal residual disease (MRD) is closely associated with prognosis in patients with acute lymphoblastic leukemia (ALL). Currently, 3 kinds of ALL-MRD detection methods commonly used at home and abroad include immunoglobulin heavy chain and T-cell receptor (IGH/TCR) gene rearrangement assessment, flow cytometry (FCM) and leukemia-associated fusion gene detection. IGH/TCR gene rearrangement assessment methods include real-time fluorescent quantitative polymerase chain reaction (RT-qPCR) and next-generation sequencing (NGS). RT-qPCR mainly detects the variable region of IGH/TCR rearrangement genes; it is about one log more sensitive than FCM, but microclones may be easily ignored leading to false negative results. NGS also detects the variable region of IGH/TCR rearrangement genes. The sensitivity of NGS-based MRD assays is higher than that of FCM and RT-qPCR, and its sensitivity is up to 10 -6, while small subclones causing recurrence can be tracked. The sensitivity of MRD was 10 -4 detected by using FCM, while FCM with ≥8-color can achieve 10 -6. However, such high level of sensitivity requires (2-5)×10 7 nucleated cells, which is rarely obtainable from remission marrows. FCM also requires substantial expertise on inspectors, and results may be easily affected by clonal evolution or phenotype shift. RT-qPCR can be used to detect fusion genes such as BCR-ABL, with a sensitivity of up to about 10 -5, but only few ALL patients carry specific gene fusions change that can be used as the monitoring of MRD. For Philadelphia chromosome-positive ALL patients, RT-qPCR is recommended to detect the level of MRD. For Philadelphia chromosome-negative ALL and T-cell ALL patients, FCM, RT-qPCR and NGS methods are all applicable.

Clinical characteristics and prognosis of 34 cases of acute myeloid leukemia with FLT3 internal tandem duplication and MLL gene rearrangement / 中华血液学杂志

Objective@#To analyze the clinical characteristics and prognosis of 34 cases of acute myeloid leukemia (AML) with FLT3 internal tandem duplication (FLT3-ITD) and MLL gene rearrangement.@*Methods@#The clinical data of 34 AML patients with FLT3-ITD and MLL gene rearrangement was compared and analyzed for the therapeutic efficacy, prognostic factors when treated with chemotherapy, chemotherapy combined with targeted therapy or allogenic hematopoietic stem cell transplantation (allo-HSCT).@*Results@#Of the thirty-four cases with median age 41 (4-71) years old, 63.6% presented with white blood cells (WBC) greater than 30×109/L, 39.4% greater than 50 × 109/L respectively on admission. M5 (35.3%) made up the highest proportion. The cytogenetic abnormality reached 61.8%, of which the complex cytogenetic abnormality accounted for 11.8%. Eleven patients (32.35%) had both FLT3-ITD and MLL gene abnormalities. In addition to FLT3 and MLL abnormalities, 23 patients (67.6%) had one or more other gene abnormalities (multiple gene abnormalities). Of the 34 cases, 29.4% patients went into complete remission (CR) after two courses of chemotherapy. 20.6% (7 patients) went into CR after 3 or more courses of chemotherapy. The rate of early relapse in the CR group was 52.9%. Patients with WBC>50×109/L or multiple gene abnormalities had a lower remission rate (7.7%, 5.4%) after two courses of chemotherapy. CR rate for the patients with more than three gene abnormalities was 0. The total 2-year overall survival (OS) in the 34 patients was 28.8% (95% CI 13.5%-46.0%) and the disease-free survival (DFS) was 27.1% (95% CI 12.5%-44.0%). Of the 18 patients treated with chemotherapy alone or chemotherapy combined with targeted therapy, 17 cases died within 2 years and 1 lost follow-up after giving up treatment. For the 16 patients received allo-HSCT, the 3-year OS was 43.4% (95% CI 13.7%-70.4%) and DFS 42.7% (95% CI 13.4%-69.7%).@*Conclusion@#AML patients with FLT3-ITD and MLL gene rearrangement often presented with M5, accompanied by hyperleukocytosis, cytogenetic or multiple gene abnormalities. Those patients were observed to have low response rate and high early relapse when treated with chemotherapy without allo-HSCT. Patients had multiple gene abnormalities may be an important poor prognostic factor. Allo-HSCT is an effective treatment which could significantly improve the prognosis and survival of AML patients with FLT3-ITD and MLL gene abnormalities.

Bone morphogenetic protein-2/type I collagen hydrogels for anterior cruciate ligament injury / 中国组织工程研究

BACKGROUND: No conclusion has yet been drawn on the effect of bone morphogenetic protein-2 (BMP-2)/collagen type I hydrogels on tendon-bone healing during the reconstruction of anterior cruciate ligament (ACL) is inconclusive. OBJECTIVE: To investigate the effect of BMP-2/collagen type I hydrogels to repair ACL injury. METHODS: ACL injury models were made in the right knees of 18 New Zealand rabbits. Model rabbits were randomized into three groups: blank control group with no intervention, control group with implantation of autologous semitendinosus tendon into the tibial and femoral tunnels, and experimental group with implantation of autologous semitendinosus tendon into the tibial and femoral tunnels combined with BMP-2/collagen type I hydrogel injection into the tibial tunnel. The Micro-CT, hematoxylin-eosin staining and Masson staining of the tendon-bone interface were conducted at 3 months after implantation. RESULTS AND CONCLUSION: (1) Micro-CT imaging examination: No obvious bone tissue regeneration around the tibial tunnel (at the opening site, 1 cm distant to the opening site, and at the widest site of the tunnel) was observed in the blank control group. Discontinuous bone regeneration in the tibial tunnel was found in the control group. In the experimental group, there was obvious tendon-bone regeneration and continuous bone connections in part of the tibial tunnel. (2) Hematoxylin-eosin staining: In the blank control group, sparse fibrous tissue and regenerated bone tissue were observed in the bone tunnel. In the control group, new bone tissues grew into the tendon, but the tendon and the surrounding tissue were loose, with a large amount of fibrocytes and the small new bone area. In the experimental group, a large number of new bone tissues were regenerated in the tendon, the tendon was intertwined with the surrounding bone tissues, and the area of new bone was increased. (3) Masson staining: In the blank control group the tunnel was partially filled with fat or fibrous tissues, and no tendon-bone interface appeared. In the control group, cartilage and fibrous tissues were visible on the tendon-bone interface, but the fibrous tissues were loosely arranged and had no close connection with the cartilage tissues. In the experimental group, fibrous-chondral-bone tissues were found on the tendon-bone interface, with fibrous tissues being tightly bound to the cartilage tissues, and mature bone tissues were visible below the cartilage tissue. These results indicate that BMP-2/collagen type I hydrogel is beneficial to ACL repair by strengthening the bone regeneration in the bone tunnel and the healing of tendon-bone junction.

Efficacy and safety of IA regimen containing different doses of idarubicin in de-novo acute myeloid leukemia for adult patients / 中华血液学杂志

Objective@#To investigate the efficacy and safety of IA regimen which contains idarubicin (IDA) 8 mg/m2, 10 mg/m2 or 12 mg/m2 as induction chemotherapy for adult patients with de-novo acute myeloid leukemia (AML) .@*Methods@#A total of 1 215 newly diagnosed adult AML patients, ranging from May 2011 to March 2015 in the First Affiliated Hospital of Soochow University and other 36 clinical blood centers in China were enrolled in the multicenter, single-blind, non-randomized, clinical controlled study. To compare the response rate of complete remission (CR) , adverse events between different dose idarubicin combined with cytarabine (100 mg/m2) as induction chemotherapy in newly diagnosed patients of adult AML.@*Results@#Of 1 207 evaluable AML patients were assigned to this analysis of CR rate. The CR rates of IDA 8 mg/m2 group, IDA 10 mg/m2 group and IDA 12 mg/m2 group were 73.6% (215/292) , 84.1% (662/787) and 86.7% (111/128) , respectively (P<0.001) . After adjusted for age, blast ratio of bone marrow, FAB classification and risk stratification, the odds ratios (95% CI) of IDA 10 mg/m2 group and IDA 12 mg/m2 group were 0.49 (0.34-0.70) and 0.36 (0.18-0.71) , as compared with the IDA 8 mg/m2 group (P<0.001, P=0.003) . In the intermediate and favorable groups, CR rates was 76.5% (163/213) , 86.9% (506/582) and 86.1% (68/79) in different doses of IDA (P=0.007) . Interestingly, IA regimen with IDA 10 mg/m2 was the only beneficial factor affecting CR in this group after adjusted for age, blast ratio of bone marrow and FAB classification[OR=0.47 (95% CI 0.31-0.71) , P<0.001]. CR rates in adverse group was 50.0% (18/36) , 60.6% (43/71) and 81.8% (18/22) respectively (P=0.089) . However, the odds ratios (95% CI) of IDA 12 mg/m2 when compared with the IDA 8 mg/m2 was 0.22 (0.06-0.80) , after adjusted for age, blast ratio of bone marrow and FAB classification. The median time (days) of neutrophil count less than 0.5×109/L in IDA 8 mg/m2 group, IDA 10 mg/m2 group and IDA 12 mg/m2 group were 14 (11-18) , 15 (11-20) and 18 (14-22) , respectively (P=0.012) and of platelet count lower than 20×109/L were 14 (7-17) , 15 (11-20) and 17 (15-21) , respectively (P=0.001) . The incidences of lung infection in the three groups were 9.8%, 13.5% and 25.2%, respectively (P<0.001) .@*Conclusions@#For young adult patients (aged 18-60 years) with AML in China, intensifying induction therapy with idarubicin 10 mg/m2 is clinically superior to IDA 8 mg/m2 and IDA 12 mg/m2 in favorable intermediate AML subgroup. However, idarubicin 12 mg/m2 is more suitable to adverse AML subgroup.

Distribution and drug resistance of pathogens at hematology department of Jiangsu Province from 2014 to 2015: results from a multicenter, retrospective study / 中华血液学杂志

Objective@#To describe the distribution and drug resistance of pathogens at hematology department of Jiangsu Province from 2014 to 2015 to provide reference for empirical anti-infection treatment.@*Methods@#Pathogens were from hematology department of 26 tertiary hospitals in Jiangsu Province from 2014 to 2015. Antimicrobial susceptibility testing was carried out according to a unified protocol using Kirby-Bauer method or agar dilution method. Collection of drug susceptibility results and corresponding patient data were analyzed.@*Results@#The separated pathogens amounted to 4 306. Gram-negative bacteria accounted for 64.26%, while the proportions of gram-positive bacteria and funguses were 26.99% and 8.75% respectively. Common gram-negative bacteria were Escherichia coli (20.48%) , Klebsiella pneumonia (15.40%) , Pseudomonas aeruginosa (8.50%) , Acinetobacter baumannii (5.04%) and Stenotropho-monas maltophilia (3.41%) respectively. CRE amounted to 123 (6.68%) . Common gram-positive bacteria were Staphylococcus aureus (4.92%) , Staphylococcus hominis (4.88%) and Staphylococcus epidermidis (4.71%) respectively. Candida albicans were the main fungus which accounted for 5.43%. The rates of Escherichia coli and Klebsiella pneumonia resistant to carbapenems were 3.5%-6.1% and 5.0%-6.3% respectively. The rates of Pseudomonas aeruginosa resistant to tobramycin and amikacin were 3.2% and 3.3% respectively. The resistant rates of Acinetobacter baumannii towards tobramycin and cefoperazone/sulbactam were both 19.2%. The rates of Stenotrophomonas maltophilia resistant to minocycline and sulfamethoxazole were 3.5% and 9.3% respectively. The rates of Staphylococcus aureus, Enterococcus faecium and Enterococcus faecalis resistant wards vancomycin were 0, 6.4% and 1.4% respectively; also, the rates of them resistant to linezolid were 1.2%, 0 and 1.6% respectively; in addition, the rates of them resistant to teicoplanin were 2.8%, 14.3% and 8.0% respectively. Furthermore, MRSA accounted for 39.15% (83/212) .@*Conclusions@#Pathogens were mainly gram-negative bacteria. CRE accounted for 6.68%. The rates of Escherichia coli and Klebsiella pneumonia resistant to carbapenems were lower compared with other antibacterial agents. The rates of gram-positive bacteria resistant to vancomycin, linezolid and teicoplanin were still low. MRSA accounted for 39.15%.

Research progress on human acute leukemia xenograft mouse models / 中国实验血液学杂志

The methods for modeling human acute leukemia in mice include xenotransplantation of human leukemia cells, retroviral transduction/transplantation, transgenesis, chemical mutagenesis and insertional mutagenesis. Establishing human acute leukemia mouse models through xenograft is an important way to study acute leukemia. This review focuses on the newest progress of studies on human acute leukemia xenograft mouse models in the regards of the immunodeficiency mouse, preconditioning, cytokines, cell transplantation, the evaluation and application of model.

Mechanism of ouabain inducing the apoptosis of T lymphoblastic leukemia Jurkat cells / 医学研究生学报

Objective Ouabain is a cardiotonic steroid that can induce the apoptosis of many tumorous cells .This study was to investigate the anti-tumor mechanisms of ouabain by observing its effects on the apoptosis of T lymphoblastic leukemia Jurkat cells and the expressions of hTERT and c-myc mRNA and protein . Methods Jurkat cells were treated with ouabain at the concentrations of 50 and 100 nmol/L for 24 and 48 hours, and those treated with 1 ×PBS served as the control .Then the apoptosis rate of the cells was detected by flow cytometry after Annexin V/PI staining, the expressions of hTERT and c-myc mRNA determined by RT-PCR, and those of hTERT and c-myc protein by Western blot . Results The apoptosis rates of the Jurkat cells in the 50 and 100 nmol/L oua-bain groups were (5.67 ±3.71)%and (9.63 ±4.83)%respectively at 24 hours, and (19.67 ±4.55)%and (37.60 ±11.89)%at 48 hours, significantly higher than (4.23 ±1.01)%in the PBS control group at 48 hours (P<0.05).Compared with the control, the expressions of hTERT and c-myc mRNA were decreased by 200%and those of hTERT and c-myc protein by 224%and 400%, re-spectively, at 48 hours (P<0.05).There was a positive correlation between the reduction of the mRNA levels and that of the protein levels of hTERT and c-myc (P<0.05). Conclusion Ouabain can down-regulate the mRNA and protein expressions of hTERT and c-myc, which may be one of the mechanisms of its induction of the apoptosis of Jurkat T lymphocyte leukemia cells .

Prognostic power of abnormal cytogenetics for multiple myeloma: a multicenter study in China / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Chromosomal abnormalities have been shown to play an important prognostic role in multiple myeloma (MM). Interphase fluorescence in situ hybridization (i-FISH) has been much more effective to identify cytogenetic aberrations in MM than conventional cytogenetic technique (CC). To clearly determine the cytogenetic features of Chinese MM patients and identify their prognostic implications, we designed a multicenter study based on i-FISH including 672 patients from 52 hospitals in China.</p><p><b>METHODS</b>All 672 patients were systematically screened for the following genomic aberrations: del(13q), IgH rearrangement, del(p53) and 1q21 amplifications.</p><p><b>RESULTS</b>The analysis showed that the chromosomal changes were detected in 22.1% patients by CC and in 82.3% patients by i-FISH. The most common abnormalities by CC were chromosome 1 aberrations (48.4%), -13/13q- (37.6%), hyperdiploidy (36.6%), hypodiploidy (30.1%) and IgH rearrangements (23.7%). The most frequent abnormalities by FISH was del(13q), which was found in 60.4% patients, whereas IgH rearrangement, 1q21 amplification and p53 deletions were detected in 57.6%, 49.0% and 34.7% cases, respectively. By statistical analysis, -13/13q- by CC was associated with low level of platelet (P = 0.015), hyperdiploidy was associated with low level of serum albumin (P = 0.028), and IgH rearrangement by FISH was associated with high level of β2 microglobulin (P = 0.019). Moreover, 1q21 amplification and del(p53) by FISH conferred a high incidence of progressive disease (PD) after initial therapy. Metaphase detection of IgH rearrangements and chromosome 1 aberrations concurrently was associated with a short progression free survival (PFS) (P = 0.036). No significant prognostic implications of other cytogenetic abnormalities were found associated with overall survival and PFS.</p><p><b>CONCLUSIONS</b>Chinese MM patients had similar cytogenetic abnormalities compared with the previous reported studies. However, the prognostic significance of FISH aberrations were not clearly determined and further study is required.</p>

Gene mutations and the phenotype of BCR/ABL-negative myeloproliferative neoplasms / 国际肿瘤学杂志

Janus kinase 2,myeloproliferative leukemia virus and tet encogene family member2 mutations affect a variety of cytokines signal transduction pathway in BCR/ABL-negative myeloproliferative neoplasms (MPN). In the influence of mutation load,co-mutation and genetic susceptibility,these mutations can induce different MPN phenotypes,and affect the characteristics of patients,the distribution of peripheral blood cells and prognosis. But how these mutations contribute to disease initiation,development,and transformation needs further reseach.

Gambogic acid induces apoptosis of Jurkat cell through the MAPK signal pathway / 中国实验血液学杂志

The aim of this study was to investigate the apoptosis-inducing effect of gambogic acid (GA) on Jurkat cells and its underlying signaling pathway. Apoptosis induced by GA and some inhibitors was assayed by Annexin V/PI doubling staining. The levels of caspase 3, caspase 8 and caspase 9 activated in living Jurkat cells were measured by flow cytometry. The expressions of caspase 3, caspase 9, p-JNK and P38 were detected by Western blot. The results showed that GA induced apoptosis of Jurkat cells in a dose-dependent manner. The positive cell number of activated caspase 3, caspase 8, caspase 9 and the levels of activated caspase 3, caspase 9, p-JNK, P38 increased after Jurkat cells were treated with GA. ROS, CaMKII, caspase 3, caspase 9, MAPKK, JNK1/2 and P38 inhibitors had some significant effect on GA-induced apoptosis. ROS, CaMKII, MAPKK, JNK1/2 and P38 inhibitors decreased the levels of activated caspase 3, caspase 9 by GA.ROS, CaMKII, MAPKK, JNK1/2 inhibitors decreased the levels of p-JNK by GA. ROS, CaMKII, MAPKK, P38 inhibitors decreased the levels of P38 by GA. It is concluded that GA induced apoptosis of Jurkat cells by activated caspases through activating of ROS-CaMKII-MAPKK-JNK/P38 pathway.

Expression and significance of CD34, CD117 on bone marrow mononuclear cells of patients with myelodysplastic syndrome / 白血病·淋巴瘤

Objective To explore the expression and significance of CD34, CD117 on bone marrow mononuclear cells of myelodysplastic syndromes (MDS). Methods Direct immunofluorescence staining was used by means of flow cytometry. 37 patients with MDS were divided into RA/RARS/RCMD subgroup, RAEB Ⅰ/RAEB Ⅱ subgroup; favorable chromosomal subgroup, poor chromosomal subgroup; intermediate-risk Ⅰ subgroup, intermediate-risk Ⅱ subgroup, high-risk subgroup respectively according to WHO classification,cytogenetic abnormalities and international prognostic scoring system (IPSS). Results CD34 and CD117 were positive respectively in 11 of 19 patients with RMRARS/RCMD, all cases in RAEB Ⅰ/RAEB Ⅱ expressed CD34 and CD117; increased expression of CD34 and CD117 was MDS grade-related. Favorable chromosomal subgroup, 14 of 22 patients were positive for CD34, CD117, all cases in poor chromosomes expressed CD34 and CD117; there was a direct relationship between phenotytic density and poor cytogenetic risk factor. CD34 and CD117 expression was present respectively in intermediate-risk Ⅰ (9/17), intermediate-risk Ⅱ (11/11) and highrisk subgroup (9/9); the phenotypic intensity also was correlated with IPSS scores. Conclusion Detection of CD34, CD117 may be a useful tool for subtyping and predicting the prognosis of MDS.

Immune changes in type 1 diabetes animal model after syngeneic bone marrow transplantation / 中国实验血液学杂志

Syngeneic bone marrow transplantation (syn-BMT), as a novel therapy for type 1 diabetes (T1D), has been used more and more widely. This study was aimed to detect the changes of peripheral CD4(+) T lymphocytes, CD8(+) T lymphocytes, CD4(+)/CD8(+) T lymphocytes and NK cells before and after T1D mice were treated with syn-BMT, and to investigate the effects of these cells in T1D and the effects of syn-BMT-inducing immunotolerance. T1D mouse model was established by multiple low dose streptozotocin injection, the syn-BMT was performed on 10 day after the onset of diabetes. The T1D model mice were divided into group of diabetic mice treated with syn-BMT and group of diabetic control mice (DC), 6 normal C57BL/6J mice were regarded as normal control group (NC). On 30 day after syn-BMT, peripheral proportion of CD4(+) T lymphocytes, CD8(+) T lymphocytes, CD4(+)/CD8(+) T lymphocytes and NK cells were detected by flow cytometry. These cells of normal control mice (NC), diabetes control mice (DC) and diabetes mice treated by syn-BMT were also detected. Blood glucose level in three groups was assayed during the whole observation period. The results showed that syn-BMT could reduce blood glucose level of T1D mice to near normal (p > 0.05). Hematopoietic reconstitution happened in a month. The proportion of peripheral CD4(+) T lymphocytes, CD4(+)/CD8(+) T lymphocytes, NK cells all increased in new-onset diabetic mice (p < 0.01), while the proportion of peripheral CD8(+) T lymphocytes decreased (p < 0.01). On 30 day after T1D mice were treated with syn-BMT, the proportion of peripheral CD4(+) T lymphocytes was significantly lower than that in DC mice (p < 0.01), but still higher than NC (p < 0.05). The proportion of CD8(+) T lymphocytes was higher than that in DC and NC mice (p < 0.01). The ratio of CD4(+)/CD8(+) T lymphocytes and proportion of NK cells were both obviously lower than that in DC and NC mice (p < 0.01). It is concluded that the syn-BMT can reverse hyperglycemia and immune disorder in diabetic mice. On early period of diabetes onset, the proportions of CD4(+) T lymphocytes and NK cells, the ratio of CD4(+)/CD8(+) T lymphocytes increase, while proportion of CD8(+) T lymphocytes decreases in peripheral blood which mye be associated with onset of diabetes.

Clinical study of elderly patients with acute promyelocytic leukemia / 白血病·淋巴瘤

Objective To investigate the clinical features, therapy and prognosis of elderly patients with newly diagnosed acute promyelocytic leukemia (APL). Methods The clinical features of 21 elderly patients and 89 patients aged ＜60 with newly diagnosed APL were retrospectively analyzed. Additionally,elderly patients were divided into different groups according to the count of white blood cell (WBC). Results There were no significant differences between elderly patients and patients aged ＜60 in the aspect of sex (male/female: 11/10 vs 47/42), WBC count (high initial WBC: 23.8 % vs 16.9 %), the percentage of bone marrow blasts plus promyelocytes (0.83±0.11 vs 0.83±0.12), complete remission (CR) rate (71.4 % vs 84.3 %),the time of CR occurrence (35.7±10.1 vs 39.1±13.5), the occurrence of retinoic acid syndrome(RAS) (14.3 % vs 22.5 %), disseminated intravascular coagulation (DIC) (52.4 % vs 34.8 %) as well as 2 years overall survival rate (72.7 % vs 80.0 %) (P ＞0.05). Of the 21 elderly patients who received inductive treatment, 5 with high initial WBC and 16 without high initial WBC. The incidences of DIC, early death in high initial WBC group were 80 %, 60 % respectively, which were higher than the group without high initial WBC (43.8 %,18.8 % respectively), whereas CR rate for the group with high initial WBC (40.0 %) was lower than that for the group without high initial WBC (81.3 %). Conclusion Elderly patients with APL could have fine prognosis as well as patients aged ＜60. The results of inductive treatment of elderly patients in high initial WBC group were poor as compared with the group without high initial WBC.

Gambogic acid induces Raji cell apoptosis in vitro and its mechanism / 白血病·淋巴瘤

Objective To study the inducing apoptosis effect of a traditional Chinese medicine gambogic acid (GA) on Raji cell line and its mechanism. Methods The effect of GA on the proliferation of human peripheral blood mononuclear cells induced by lipopolysaccharide (LPS) was analyzed. Raji cells were treated with GA at different concentrations and times, and the inhibitory effect was detected by MTT assay.Apoptosis induced by GA was observed by Annexin V/PI doubling staining and flow cytometry assay.Mitochondrial membrane potential was measured by JC-1 assay. Activated Caspase-3, Caspase-8 and Caspase-9 in living Raji cells were measured by caspGLOWTM fluorescein staining kit and quantificated by flow cytometry. Results After incubation with GA, the proliferation rates of both normal blood mononuclear cells and Raji cells were dramatically inhibited in a concentration dependent manner. GA induced Raji cells to undergo apoptosis. GA decreased the mitochondrial membrane potential of Raji cells. GA increased the level of activated caspase 3, caspase 8, caspase 9 for 0.37 %, 33.57 %, 18.27 % in 24 h and 28.2 %, 69.2 %,76.7 % in 48 h respectively. Conclusion GA have an inhibitory effect on Raji cells, and can trigger apoptosis of Raji cells through both intrinsic and extrinsic pathways.