Regulatory effects of ADT-OH on the proliferation of neural precursor cells / 中国组织工程研究

BACKGROUND: Researchers believe that hydrogen sulfide (H2S), as an important cell protective molecule, may become a new treatment method to restore the physiological function of diseased cells or organ systems through the artificial regulation of endogenous H2S biosynthesis or in vitro administration of H2S donor. ADT-OH is a slow-release donor of H2S that can improve the survival rate of hippocampal nerve cells with glutamate-induced injury, but studies on the proliferation of cerebral cortical neural precursor cells are rare. OBJECTIVE: To investigate the effect of ADT-OH on the proliferation of neural precursor cells in embryonic cerebral cortex. METHODS: Neural precursor cells from cerebral cortical ventricular zone and subventricular zone of embryonic mice at embryonic 14.5 days were isolated. Neural precursor cells from one fetal mouse were inoculated into one well (24-well plate), and cultured with the medium containing 100 μmol/L ADT-OH. The size and number of neural spheres per well were measured at 3 days after culture. The proliferation rate of cultured neural precursor cells was detected by BrdU labeling. The proliferation of the cells was further verified by immunofluorescence staining with the specific antibody Ki67. The expression of cyclin D1 was finally detected by western blot assay. RESULTS AND CONCLUSION: Our experimental results showed that ADT-OH could promote the formation of neural spheres, and further detection by BrdU and Ki67 antibody showed that ADT-OH could promote the proliferation rate of neural precursor cells. Meanwhile, the expression of cyclin D1, a proliferation-related gene, was up-regulated in neural precursor cells after ADT-OH treatment. Overall, ADT-OH may promote the proliferation of neural precursor cells by regulating the expression of cyclin D1.

Study of iron overload assessment by T2* magnetic resonance imaging in patients with myelodysplastic syndromes / 中华血液学杂志

Objectives: To analyze the cardiac T2* value, liver iron concentration (LIC) , and related laboratory parameters in myelodysplastic syndrome (MDS) with iron overload and evaluate the changes of organ functions after iron chelation therapy. To explore the value of magnetic resonance imaging (MRI) T2* in making early diagnosis and assessing organs iron overload. Methods: Retrospective investigation was used to observe the cardiac T2* value, LIC, iron metabolism parameters and related laboratory parameters of 85 MDS patients from Nov 2014 to Jan 2018. Among them, 7 MDS patients with Low/Int-1 have received iron chelation therapy for 6 months during two MRI examinations. The above parameters were collected before and after iron chelation therapy for comparison. Results: Correlations were found between heart T2* value and age (rs=-0.290, P=0.007) and left ventricular ejection fraction (LVEF) (rs=0.265, P=0.009) . There was a significant negative correlation between heart T2* value and blood transfusion units (rs=-0.701, P<0.001) . There was a significant positive correlation between LIC and serum ferritin (SF) (rs=0.577, P<0.001) . There was also a correlation between LIC and ALT (rs=0.268, P=0.014) and blood transfusion units (rs=0.244, P=0.034) . There was no correlation between heart T2* and pro-BNP, SF (all P>0.05) , and no correlation between LIC and age (P>0.05) . The increase of heart T2* between the normal and abnormal groups was statistically significant (P=0.005) , but the iron overload ratio of the heart T2*<20 ms was not significant between the two groups. There was statistical significance in the proportion of severe liver iron overload (LIC>15 mg/g DW) (P=0.045) . After iron chelation therapy, the values of SF, transferrin saturation, ALT, AST, pro-BNP and LIC of 7 patients were decreased compared with values before iron chelation therapy, and the peripheral blood cell level was increased. However, the changes of LVEF and T2* values after iron chelation were not obvious. Conclusion: MRI T2* may be a predictor of iron overload in patients with MDS in early stage, and may be more valuable compare with LVEF, SF and other laboratory indicators. The safety and repeatability of MRI cardiac T2* examination are recognized, and it can be used as an ideal detection for patients with iron overload.

Clinical therapeutic efficacy of rituximab for relapsed and refractory idiopathic thrombocytopenic purpura / 中国实验血液学杂志

The aim of this study was to evaluate the effect of rituximab treatments for refractory and relapsed idiopathic thrombocytopenic purpura (ITP). 18 patients with refractory and relapsed ITP who received 22 courses of rituximab treatments from January 2007 to December 2010 were analyzed retrospectively. Rituximab was given at a dose of 375 mg/m(2) intravenously weekly for a continuous 4 weeks. The results indicated that responses were achieved in 15 of 22 (68%) courses, out of which complete responses were achieved in 10 of 22 (45%) courses, partial and minimal responses were achieved in 5 of 22 (23%) courses, and no responses were achieved in 7 of 22 (32%) courses. The median time of response was 3 weeks (1 - 17 weeks) from the start of treatment and median duration of response was 13 weeks (1 week - 42 months). The responses were mostly short-sustained and follow-up median time was 20 months (1 - 52 months). The responses of 8 patients (36%) sustained for over 6 months, 6 patients (27%) sustained for over 1 year, and 4 patients also showed sustained response at last visit of follow-up. Previous splenectomy resulted in a poor response (P = 0.037). Patients who failed in rituximab treatment and prior received multiple treatments including splenectomy, had a poor response to further therapies. It is concluded that rituximab is well tolerated by patients and is useful in some patients with relapsed and refractory ITP, however, only about 20% patients can achieve sustained remissions. The patients who failed in rituximab treatment has a poor response to further treatment.

Expression of p57kip2 in patients with de novo myelodysplastic syndrome and its relationship with SDF-1/CXCR4 axis / 中国实验血液学杂志

This study was purposed to explore the expression of p57kip2 in the bone marrow of patients with de novo myelodysplastic syndrome (MDS) and its role in MDS pathogenesis, as well as the relationship between the expression of p57kip2 and SDF-1/CXCR4 signal. The expression of p57kip2 and CXCR4 in 67 de novo MDS patients was measured by real-time quantitative PCR. The percentage of CD34(+) cells in the bone marrow from MDS patients was measured by flow cytometry. 18 healthy volunteers were recruited for control. The effect of SDF-1 on p57kip2 expression in bone marrow mononuclear cell (BMMNC) from MDS or normal controls was investigated in vitro, and difference between them was compared. The results showed that low-risk MDS and high-risk MDS displayed a significant reduction of p57kip2 mRNA expression in BMMNC compared with that in control group (P < 0.001) and there was a negative correlation between p57kip2 expression and percentage of CD34(+) (r = -0.458, P < 0.001); the patients with abnormal karyotype showed lower expression of p57kip2 gene, compared to patients with normal karyotype (P = 0.045). Although the expression of CXCR4 had no difference between MDS patients and normal controls, a positive correlation between p57kip2 and CXCR4 in MDS patients was still found (r = 0.609, P < 0.001). Moreover, SDF-1 increased p57kip2 expression in normal BMMNC in dose-dependent manner, but BMMNC from MDS patients showed no response to SDF-1. SDF-1-induced p57 expression was blocked by AMD3100. It is concluded that the low expression of p57 gene in MDS may play a role in the pathogenesis of MDS. Furthermore, SDF-1-induced p57kip2 expression in BMMNC, and the decreasing response of BMMNC to SDF-1 may contribute to the low expression of p57kip2 in MDS patients.

Cytogenetic study of autosomal monosomies among myelodysplastic syndrome patients / 中国实验血液学杂志

Monosomic karyotype (MK) has recently been associated with poor prognosis of myelodysplastic syndromes (MDS). The objective of the current study was to investigate the prevalence and spectrum of autosomal monosomies in an unselected cohort of patients with known or suspected MDS by using retrospective analysis. The results showed that bone marrow cytogenetic studies (1532 cases) were performed between 2004 and 2012, and an abnormal karyotype was found in 538 cases (35.1%). In the 538 cases, 202 (37.5%) cases had autosomal monosomies including sole (n = 47, 23.3%), part of two (n = 33, 21.3%) or more (n = 122, 78.7%) anomalies. Almost all 22 autosomes were involved, but monosomy 7 was by far the most frequent, constituting 66.1% of all isolated monosomies and the highest fraction of those with two or more abnormalities. Other recurrent sole monosomies included chromosomes 20 (15.0%) and 13 (8.5%). Monosomy 13 (12.5%), 18 (8.3%), 20 (6.3%), 17 (7.3%), 21 (5.2%), 5 (5.2%) and 12 (5.2%) were also recurrent in the setting of 3 abnormalities. Bone marrow histology and clinical information were reviewed in all cases with isolated monosomy; associated clinical phenotypes were found in RCMD (n = 20, 13 were -7), RAEB (n = 12, 11 were -7), RA (n = 9, 3 were -7) and chronic myelomonocytic leukemia (CMML, n = 6, 4 were -7) cases. Sole monosomy 20 (n = 7, RA 3 case and RCMD 4 cases) was not detected in RAEB or CMML cases. It is concluded that the presence of at least 1 autosomal monosomy was documented in approximately 37.5% of all abnormal cases, which has potential impact on a more than trivial fraction of patients with MDS. The preponderance of monosomy 7 implicates a pathogenetic role for haploinsufficiency of genes associated with chromosome 7. The rarity of sole monosomy involving other chromosomes other than 7, 20, and 13 suggests that haploinsufficiency involving entire chromosomes is detrimental to cell survival, unless their effect is overcome by the presence of other genetic changes that are often associated with additional chromosomal abnormalities. The observation is consistent with the usually favorable prognostic profile associated with sole monosomy 20.

Comparison of bone marrow biopsy and smear efficacy in patients with multiple myeloma / 中国实验血液学杂志

This study was aimed to explore the significance of the bone marrow biopsy for the diagnosis of multiple myeloma. Bone marrow smears and bone marrow biopsy originated from 279 cases of multiple myeloma were detected and compared in term of bone marrow hyperplasia, bone marrow plasma cell infiltration, proliferation mode, pathological changes in the bone marrow stroma and myelofibrosis. The results indicated that the levels of proliferation in bone marrow biopsy was significantly higher than that in bone marrow smears. Plasma cell proliferation mode in bone marrow biopsy was not completely consistent with the proportion of plasma cells in bone marrow smears. The myelofibrosis level displayed influence on the consistency of the proliferation between bone marrow smears and biopsies. It is concluded that as compared with bone marrow smears the bone marrow biopsy can more accurately reflect the levels of bone marrow hyperplasia and bone marrow plasma cell infiltration, proliferation mode and so on. Bone marrow biopsy is valuable for multiple myeloma diagnosis.

The affection of bisphosphonates combined with chemotherapy on bone metabolism index in multiple myeloma / 中华血液学杂志

<p><b>OBJECTIVE</b>To explore the clinical value of urine N-telopeptides of type I collagen (uNTX) and serum bone specific alkaline phosphatase (sBAP) in myeloma bone disease, and to understand the role of bisphosphonates therapy for multiple myeloma(MM) osteolytic bone lesion.</p><p><b>METHODS</b>Thirty-three MM cases were treated with bisphosphonates combined with chemotherapy (considered as treatment group), and 20 untreated MM cases with chemotherapy alone considered as control group. uNTX was detected by ELISA, and sBAP by chemiluminescence analysis.</p><p><b>RESULTS</b>(1) There was no significant differences in uNTX between treatment \[(173.74 ± 14.55) µg/L\] and control groups \[(129.79 ± 12.13) µg/L\] before bisphosphonates treatment (P > 0.05). After six-month treatment, there was significant differences between two groups \[(85.71 ± 8.23) µg/L and (121.59 ± 12.43) µg/L, respectively\] (P < 0.05); Meanwhile, there were significant differences in uNTX between before and after three-month treatment (P = 0.045) and between before and after six-month treatment (P < 0.01) in treatment group. (2) There was no significant differences in sBAP concentration between treatment and control groups \[(4.78 ± 0.55) µg/L and (8.42 ± 1.32) µg/L, respectively\] before treatment (P > 0.05). After six-month treatment, there were significant differences between them \[(16.01 ± 0.52) µg/L and (9.62 ± 1.29) µg/L, respectively\] (P < 0.01). Meanwhile, in treatment group, there was no significant differences between before and after three-month treatment (P > 0.05), but being significant difference between before and after six-month treatment (P < 0.01).</p><p><b>CONCLUSION</b>uNTX, sBAP are important early sensitive index to measure the osteolytic bone lesion in MM patients. Bisphosphonates can significantly improve the osteopathy in MM cases.</p>

Correlation between clinical outcome of 115 patients with idiopathic thrombocytopenic purpura and megakaryocyte counts in bone marrow biopsy / 中国实验血液学杂志

The aim of study was to explore the influence of the number of megakaryocytes in bone marrow smear and trephine biopsy on clinical outcome of idiopathic thrombocytopenic purpura (ITP). The clinical outcome of 115 patients with ITP was compared by different clinical subtype, number of blood platelet, number of megakaryocyte in bone marrow smear and trephine biopsy. The results showed that: (1) the clinical outcome of acute ITP was better than that of chronic ITP, the short clinical outcome of acute ITP and chronic ITP were 86.6% vs 60.4% respectively (p < 0.01), the long clinical outcome of them were 82.5% vs 68.9% respectively (p < 0.05); (2) different number of blood platelet at occurrence of diseases had no obviously influence on clinical outcome of patients with ITP; (3) all cases were subgrouped according to number of megakaryocyte in bone marrow smear, the number of megakaryocyte in bone marrow smear less than 7/4.5 cm(2) was defined as group I, the number of megakaryocyte between 7/4.5 cm(2) to 35/4.5 cm(2) was defined as group II, and the number of megakaryocyte in bone marrow smear greater than 35/4.5 cm(2) was defined as group III. The effective rates of 3 groups in short term treatment were 53.3%, 73.8% and 86.2% respectively, and there were statistical difference between these 3 groups (p < 0.01), the effective rates of these 3 groups in long term treatment were 42.8%, 84.6% and 85.5% respectively, and there was no statistical different between group II and group III (p > 0.05), but both had statistical difference, as compared with group I (p < 0.01). (4) all cases were subgrouped by the number of megakaryocyte in trephine biopsy on time of disease occurrence, the number of megakaryocyte in bone marrow smear less than 8/mm(2) was defined as group I, the number of megakaryocyte between 8/mm(2) to 15/mm(2) was defined as group II, the number of megakaryocyte greater than 15/mm(2) was defined as group III. The effective rate of these 3 groups in short term treatment were 53.8%, 85.0% and 90.3% respectively, group II and III had no statistical difference each other (p > 0.05), but both groups had statistical difference as compared with group I (p < 0.01). Effective rate of these 3 groups in long term treatment were 33.3%, 63.1% and 87.9% respectively, and there were statistical difference between them (p < 0.01). (5) the number of blood platelet at time of disease occurrence was not related to number of megakaryocyte in bone marrow smear and in trephine biopsy section(r = 0.31, p > 0.05; r = 0.41, p > 0.05). The number of megakaryocyte in bone marrow smear had positive correlation to that in trephine biopsy slides (r = 0.52, p < 0.01). In case to use single factor Logistic regression, the results showed that number of megakaryocyte in bone marrow smear and trephine biopsy had obvious influence on long term treatment of ITP. It is concluded that the number of megakaryocyte in trephine biopsy can be used as a available supplement method for bone smear, and can forecast the therapeutic effect of patients with ITP.

Yield of CD34(+) cells in graft can be increased significantly by G-CSF used at appropriate time after chemotherapy for AutoPBSCT / 中国实验血液学杂志

This study was aimed to investigate the influence of timing using G-CSF after chemotherapy on graft yield of mobilized peripheral blood stem cells for autoPBSCT. 39 patients with lymphoma or multiple myeloma (MM) received the same chemotherapy mobilization regimen, including CTX 400 mg/m² d1; VLB 2 mg/m(2) d1; Ara-C 60 mg/m ²× d1-5; VP-16 60 mg/m² × d1-5; and prednisone 40 mg/m² × d1-5. The historical control group (12 cases) received G-CSF subcutaneously (filgrastim) at the first restoration after the initial nadir of the peripheral WBC count. The experimental group (27 cases) received G-CSF during the steady rise of the WBC count (end of fluctuating after initial nadir). G-CSF was given in a single daily subcutaneous dose of 5 µg/kg until the final PBSC apheresis. When the peripheral WBC and mononuclear cell (MNC) counts reached 10 × 10⁹/L and 1.0 × 10⁹/L respectively, leukapheresis was carried out using the COBE Spectra blood cell separator. The results indicated that despite there was comparable treatment with alkylating agents between 2 groups, a significantly increased yield of CD34 positive cells was observed in the experimental group (26.4 × 10⁶/kg), as compared to the historical control group (3.1 × 10⁶/kg) (p = 0.0031). It is concluded that the appropriate timing for the use G-CSF mobilization after chemotherapy is important to increase the CD34(+) cell yield in auto-graft.

Efficacy of induction chemotherapy for patients with high-risk myelodysplastic syndrome (MDS) or MDS-transformed acute myeloid leukemia with CHG regimen and its comparison with regimen GAG and HA / 中国实验血液学杂志

This study was aimed to investigate the efficacy of moderate intensity regimen, CHG (homoharringtonine, cytarabine and granulocyte colony-stimulating factor (G-CSF)) on the patients with high-risk MDS or MDS-transformed acute myeloid leukemia. 30 newly diagnosed adult patients with high-risk MDS or MDS-transformed AML were enrolled in this clinical trial to evaluate the efficacy of sequential low-dose homoharringtonine/cytarabine chemotherapy combined with G-CSF priming. Homoharringtonine and Ara-C were injected intravenously at doses of 1 mg and 25 mg daily for 14 consecutive days respectively, G-CSF was injected subcutaneously once daily at a dose of 300 microg on 12 hours prior to chemotherapy and continued given until the end of chemotherapy or when the peripheral WBC count reached > 20 x 10(9)/L. This regimen was given only for one course, and followed by conventional chemotherapy as maintenance or consolidation therapy when CR achieved. 33 patients with high- risk MDS and MDS-transformed AML were injected aclarubicin/Ara-C intravenously at doses of 10 mg and 25 mg for 8 and 14 consecutive days respectively, G-CSF was used at the same dose and the same way as the CHG regimen. 33 patients with high-risk MDS and MDS-transformed AML were treated with HHT/Ara-C intravenously at doses of 2 - 3 mg and 100 - 150 mg daily for 7 consecutive days respectively, G-CSF was injected when WBC count was below 4 x 10(9)/L, and it was stopped to be used when WBC count was > 4 x 10(9)/L. The results showed that (1) 14 patients achieved complete remission (CR) (46.67 %) and 7 patients achieved partial remission (PR) (23.33 %) with one course of CHG regimen, total effective rate was 70%; 14 patient achieved CR (42.4%) and 9 patients achieved PR (27.3%) with one course of CAG regimen, total effective rate was 69.7%; 7 patient achieved CR (33.3%) and 3 patients achieved PR (9.1%) with one course of HA regimen, total effective rate was 42.4%. There was no statistical difference between the effective rate of CHG and CAG, but difference was significant between CHG and HA. (2) Agranulocytosis (neutrophil < 0.5 x 10(9)/L) occurred in 12 cases (40%) of CHG-treated patients with a mean 8 days of agranulocytic period, so the infectious complications were less serious and tolerable without treatment-related death. (3) Among 14 out of 30 patients with CR, 9 relapsed, the mean duration from CR to replace was 8.2 months. All relapsed patients reusing CHG regimen did not achieved CR again. (4) Among 13 cases with CR, 6 patients just received HA or DA regimens as consolidatory and intensive chemotherapy after CR have relapsed, the mean CR time was only 6.1 months. Otherwise, the mean CR time of 7 CR patients received alternative succeeded chemotherapy containing mitoxantrone/idarubicin/THP/homoharringtonine/daunorubicin/aclarubicin after CR was 10.6 months; and among them 4 are still in continuous CR. It is concluded that the CHG chemotherapy regimen has a similar effect with CAG but better than HA, and in a saft chemotherapy regimen with slight myelosuppression in clinical application, strong and alternative succeeded chemotherapy is necessary for CR patients to keep longer CR and survival.

Selection of surgical procedure for the treatment of idiopathic scoliosis / 中华外科杂志

<p><b>OBJECTIVES</b>To discuss and evaluate the selection of surgical procedure for the treatment of idiopathic scoliosis according to the location and degree of the deformity.</p><p><b>METHODS</b>175 patients with idiopathic scoliosis underwent surgical treatment with correction and fusion. The patients were divided into four groups according to the location and degree of the deformity and four different procedures were used for each group. For each group, the blood loss, surgery time, correction rate, loss of correction at final follow up and complications were compared and analyzed.</p><p><b>RESULTS</b>All patients underwent surgery safely and no neurological complication occurred. The correction rate was 81% for Group I, 86% for Group II, 68% for Group III and 72% for Group IV. All patients were followed up at least 2 years and the average time was 38 months (24 approximately 52).</p><p><b>CONCLUSION</b>Proper selection of surgical procedure according to the location and degree of the scoliotic deformity, satisfactory results can be achieved in the treatment of idiopathic scoliosis.</p>