Combination of rabbit antithymocyte globulin and cyclosporine A as first-line therapy for adult severe aplastic anemia / 中华血液学杂志

<p><b>OBJECTIVE</b>To analyze the efficacy and side-effects of combination of rabbit antithymocyte globulin (ATG) and cyclosporine A (CsA) as the first-line immunosuppressive therapy (IST) for adult severe aplastic anemia (SAA) patients.</p><p><b>METHODS</b>Adult SAA or very severe aplastic anemia (VSAA) patients treated with rabbit ATG + CsA as first line therapy in our hospital from 2003 to 2008 were retrospectively analysed and the therapeutic response relevant factors were analysed.</p><p><b>RESULTS</b>Seventy-nine patients were enrolled. Of all these patients, 6 died within 3 months after IST. The overall response rate was 82.2% and the median time to transfusion independent was 60 days. The therapeutic response rate in 32 SAA patients (100%) was significantly higher than that in 41 VSAA cases (68.3%) (P = 0.001). Patients with neutrophil response to G-CSF treatment had a higher IST response rate than those without response to G-CSF (100% vs 67.5%, P = 0.001). Sixty-one patients (77.2%) occurred serum sickness reaction. Three patients relapsed and two developed clonal hematological abnormalities after IST. The 3-year overall survival for all the patients was 88.9%.</p><p><b>CONCLUSIONS</b>Rabbit ATG in combination with CsA as first-line IST for adult SAA can lead to excellent treatment outcomes with minor adverse effects.</p>

Methylation and expression of RUNX3 gene promoter in papillary thyroid carcinoma / 中华耳鼻咽喉头颈外科杂志

<p><b>OBJECTIVE</b>To study the relationship between status of methylation of human runt-related transcription factor 3 (RUNX3) gene promoter in papillary thyroid carcinoma (PTC).</p><p><b>METHODS</b>Methylation-specific PCR and immunohistochemical SP technique were used to detect the methylation of RUNX3 gene promoter and expression of its protein in 56 cases of PTC and their matched adjacent non-carcinous epithelium (NCE).</p><p><b>RESULTS</b>In NCE, there was no methylation of RUNX3 gene promoter, while in PTC the methylation rate was 35.7%(20/56), which was related to the tumor TNM stage, pathological grade and lymph node metastasis (P < 0.05). The positive rates of RUNX3 protein expression in NCE and PTC were 100.0% and 60.7%, respectively, with a significant difference (χ(2) = 27.378, P < 0.05). In PTC, the positive rates of RUNX3 protein expression in gradeI and grade II were 70.0% and 37.5%, respectively (P < 0.05); the rates were 46.7% and 76.9% in lymph node metastasis group and no metastasis group, respectively (P < 0.05). Moreover, there was a distinct correlation between methylation of RUNX3 gene promoter and expression of its protein (χ(2) = 21.62, P < 0.01).</p><p><b>CONCLUSIONS</b>Methylation of promoter might be one of the important factors of inactivation of RUNX3 gene, and might play an important role in carcinogenesis and progression of PTC.</p>

Expression of Piwil2 and its relationship with tumor invasion and metastasis in papillary thyroid carcinoma / 中华耳鼻咽喉头颈外科杂志

<p><b>OBJECTIVE</b>To study the expressions of Piwil2 protein and mRNA in papillary thyroid carcinoma (PTC) and the relationship between Piwil2 and the invasion and metastasis of PTC.</p><p><b>METHODS</b>Immunohistochemistry and in situ hybridization were used to detect the expression of Piwil2 protein and mRNA in 60 cases of PTC with the matched adjacent non-cancerous epithelium (NCE).</p><p><b>RESULTS</b>The positive rates of Piwil2 protein expression in PTC and NCE were 88.3% (53/60) and 10.0% (6/60) respectively, with significant difference (χ² = 73.654, P < 0.01). The positive rates of Piwil2 mRNA expression in PTC and NCE were 85.0% (51/60) and 6.7% (4/60) respectively, also with significant difference (χ(2) = 74.148, P < 0.01). Up-regulated expressions of Piwil2 protein and mRNA were related to the invasion and metastasis of PTC (P < 0.05).</p><p><b>CONCLUSIONS</b>Piwil2 may play a role in the invasion and metastasis of PTC.</p>

The significance of hematopoietic cell genetic instability in aplastic anemia / 中华血液学杂志

<p><b>OBJECTIVE</b>To evaluate bone marrow hematopoietic cells genetic instability (BMHCGI) in patients with aplastic anemia (AA) and to explore its influence on immunosupressive therapy for AA and significance on late clonal hematologic disorders.</p><p><b>METHODS</b>Genetic instability of bone marrow mononuclear cells (BMMNC) was measured by Comet assay. The relationship between bone marrow failure parameters and genetic instability results was evaluated. The reciprocity of genetic instability and treatment responses to immunosuppressive therapy (IST) was investigated.</p><p><b>RESULTS</b>Comet assay parameters \[tail moment (TM), olive TM (OTM), comet %\] of AA patients were significantly higher than that of control group (P < 0.05). There was no statistic correlation of comet parameters of severe AA (SAA) BM hematopoietic cells with age, gender and peripheral blood cell count (P > 0.05). For the treatment response rate at six months after IST there was no statistical difference between comet cells of < 21.64% and of >/= 21.64%, and so did between OTM < 1.58 and >/= 1.58 in SAA patients. IST had no effect on SAA BMHCGI, whereas, the Comet%, TM and OTM in SAA PR patients and Comet% in CR patients were significantly decreased than those before treatment. Comet parameters of two SAA patients were significantly increased before the development of clonal cytogenetic abnormalities.</p><p><b>CONCLUSIONS</b>Increased BMHCGI may be one of the elements in the pathogenetic mechanisms in AA. The genetic instability is irrelevant to the SAA patients overall response rate of IST at six months, but IST can alleviate the genetic instabilities in responded SAA patients.</p>

The clinical and laboratory characteristics of T cell large granular lymphocyte leukemia / 中华血液学杂志

<p><b>OBJECTIVE</b>To analyze the characteristics of T-cell large granular lymphocyte leukemia (T-LGLL).</p><p><b>METHODS</b>Retrospectively analyze the clinical and laboratory data of 27 patients with T-LGLL diagnosed between 1999 and 2007 in our hospital.</p><p><b>RESULTS</b>The median age at diagnosis was 48 years. All patients were symptomatic, mainly complaining of fatigue. Of the 27 patients, 14 (51.9%) had splenomegaly, and 4(14.8%) hepatomegaly. Rheumatoid arthritis was not present in any patients. The most frequent hematological abnormality was anemia (24 patients, 88.9%) with a median Hb level of 57.5 g/L. Pure red cell aplasia was found in 18 patients (66.67%). The median WBC count was 4.24 x 10(9)/L and 19 cases were neutropenia (ANC < 1.5 x 10(9)/L). The median LGL count in peripheral blood was 1.45 x 10(9)/L and most of them (77.8%) were less than 2.0 x 10(9)/L. Twenty-two patients (81.5%) showed the CD3+ CD8+ CD57+ CD56(-) LGL phenotype. With immunosuppressive therapy, 91.3% of patients responded and complete hematological remission rate was 65.2%.</p><p><b>CONCLUSION</b>T-LGLL mainly presented with anemia and complete hematological remission rate was 65.2%. Pure red cell aplasia was commonly associated with the disease. The patients had a good response to immunosuppressive therapy.</p>

Clinical and hematological features of congenital dyserythropoietic anemia type I / 中华血液学杂志

<p><b>OBJECTIVE</b>To analyze the clinical and laboratory features of patients with congenital dyserythropoietic anemia type I (CDA-I), and improve the clinical diagnostic accuracy.</p><p><b>METHODS</b>The clinical and hematological features of 5 patients diagnosed as CDA-I in our hospital between July 2002 and July 2007 were analyzed retrospectively, and the related literatures was reviewed.</p><p><b>RESULTS</b>Five CDA-I patients, 1 male and 4 females, all had a long history of varied degree of chronic anemia. One patient had congenital malformations, 3 jaundice and 4 hepatosplenomegaly. Bone marrow specimens invariably showed hypercellularity due to erythroid hyperplasia with megaloblastic changes, irregularly shaped nuclear, and chromatin bridges in 0.2% to 0.6% of all erythroblasts. All the 5 patients' bone marrow erythroblasts showed spongy heterochromatin appearances (swiss-cheese) with electron microscopy examination. There was no morphologic abnormality in the granulocytes and megakaryocytes. Serum ferritin levels were increased in 3/4 patients. One patient had been misdiagnosed as hereditary spherocytosis and performed splenectomy in the local hospital with no improvement in Hb level.</p><p><b>CONCLUSIONS</b>CDA-I is a rare congenital anemia characterized by ineffective erythropoiesis, jaundice, hepatosplenomegaly and iron overload, and may be misdiagnosed. Keeping these manifestations in mind should avoid misdiagnosis.</p>

Combination of rabbit antithymocyte globulin plus cyclosporin A as first-line immunosuppressive therapy for the childhood with severe aplastic anemia / 中华血液学杂志

<p><b>OBJECTIVE</b>To analyse the efficacy and side-effects of rabbit antithymocyte globulin (ATG) and cyclosporin A (CsA) as the first-line therapy for childhood severe aplastic anemia (SAA).</p><p><b>METHODS</b>Seventy-one childhood SAA patients treated with rabbit ATG + CsA as first line therapy were retrospectively analysed.</p><p><b>RESULTS</b>Seventy-one SAA patients, including 38 SAA and 33 very severe aplastic anemia (VSAA), were enrolled. The median age was 12 years. Of these patients, 3 died within 3 months after the immunosuppressive therapy (IST). The overall response rate was 67.6% (46/68) and the median time to transfusion independent was 53 days. Thirty-three patients (48.5%) obtained remission in 3 months after the IST and 45 (67.2%) in 6 months. The response rates were 57.7% (15/26), 56.5% (13/23) and 94.7% (18/19) for patients less than 10 years old, 10 - 15 year-old and 15 - 18 year-old, respectively. Sixty patients suffered from serum sickness on the IST. Three patients relapsed and another 3 unrespond patients received retreatment of IST, and one patient progressed to myelodysplastic syndromes (MDS).</p><p><b>CONCLUSION</b>Rabbit ATG in combination with CsA as first line therapy for childhood SAA/VSAA can lead to overall response rate of 67.6% with minor adverse effects.</p>

Expression of a tumor related gene chp2 in leukemia cells / 中国实验血液学杂志

The purpose of this study was to investigate the expression feature of a human tumor related gene chp2 in leukemia primary cells and leukemia cell lines, real-time quantitative PCR (RQ-PCR) was performed to detect the expression level of chp2 gene in peripheral blood mononuclear cells from 10 healthy individuals (as control) and 24 cases of leukemia, and in 4 kinds of leukemia cell lines. The results showed that the detection rate of chp2 gene in 10 normal controls was 80%, positive expression was (0.744 +/- 0.682) x 10(5) cps/microl. The expression levels of chp2 mRNA leukemia primary cells and leukemia cell lines were significantly higher than that in the normal control (p < 0.05). The expression levels of chp2 mRNA were higher in AML cells (7 cases), CML cells (6 cases), ALL cells (7 cases) and CLL cells (4 cases), and their expression levels were (11.637 +/- 5.588), (6.122 +/- 3.785), (4.262 +/- 2.561) and (3.434 +/- 1.974) x 10(5) cps/microl respectively. Gene chp2 positively expressed in four kinds of leukemia cell lines, and the expression levels in K562 cells, Jurkat cells, HL-60 cells and M07e cells were (5.243 +/- 1.852), (4.463 +/- 1.621), (4.137 +/- 1.837) and (2.578 +/- 1.137) x 10(6) cps/microl respectively. The expression level in leukemia cell lines was higher than that in primary cells. It is concluded that the human tumor related gene chp2 expression in leukemia primary cells and leukemia cell lines significantly increase, which may play an important role in growth process of leukemia cells.

Investigation on nutritional intakes for hospitalized children with blood disease / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To investigate the diet and nutritional status of hospitalized children with blood disease in order to provide nutritional guidelines.</p><p><b>METHODS</b>The patients' daily dietary intakes, including breakfast, lunch, dinner and additional meals, were recorded in detail for seven consecutive days. The intake amount of various nutrients was calculated using the dietary database.</p><p><b>RESULTS</b>The majority of children with blood disease showed inadequate intakes of calories [mean 1825.81 kCal/d, 73.62% of the recommended intake (RNI)] and protein (mean 67.68 g/d, 81.34% of RNI). Intakes of vitamin E and riboflavin were adequate, but intakes of vitamin A, thiamine and vitamin C (66.67%, 77.78% and 69.89% of RNI, respectively) were inadequate. Iron and selenium intakes were adequate, but calcium and zinc intakes (41.11% and 56.21% of RNI, respectively) were grossly inadequate.</p><p><b>CONCLUSIONS</b>Hospitalized children with blood disease had decreased dietary intakes of calories, protein, vitamin A, vitamin C, thiamin, calcium and zinc. The dietary pattern and nutritional intake need to be improved.</p>

The clinical characteristics of T cell large granular lymphocyte leukemia associated with pure red cell aplasia / 中华血液学杂志

<p><b>OBJECTIVE</b>To analyze the characteristics of acquired pure red cell aplasia (PRCA) secondary to T cell large granular lymphocyte leukemia (T-LGLL).</p><p><b>METHODS</b>Fourteen patients with T-LGLL associated with PRCA between 2000 and 2006 in our hospital were retrospectively analyzed.</p><p><b>RESULTS</b>The median age at diagnosis was 61 years with equal gender distribution. The PRCA had indolent process, mainly presenting with anemia. Of the 14 patients, 9 had mild to moderate splenomegaly, one hepatomegaly and one lymphadenopathy. The median Hb level was 61.5 g/L and the median WBC count 4.3 x 10(9)/L. The median percentage and count of LGL in peripheral blood were 0.36 and 1.9 x 10(9)/L respectively. The median percentage of LGL in BM was 0.165 (0.085 - 0.410). Some patients had serologic abnormalities. All the 12 cases with available bone marrow cell cytogenetics showed normal karyotypes. With cyclosporine A or glucocorticoid immunosuppressive therapy, the overall response was 91%.</p><p><b>CONCLUSION</b>T-LGLL was one of the major causes of acquired PRCA. This type of PRCA has the similar clinical and laboratory feature to that of other type of PRCA and has a good response to immunosuppressive therapy.</p>

The impact of immunosuppressive therapy on genetic instabilities of bone marrow hematopoietic cells in patients with aplastic anemia / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate the impact of immunosuppressive therapy (IST) on genetic instabilities of bone marrow hematopoietic cells (BMHCs) in patients with aplastic anemia (AA).</p><p><b>METHODS</b>Comet assay as used to detect genetic instabilities of hematopoietic cells from patients, and the percent of DNA in comet tail (TDNA), tail length (TL), tail moment (TM), olive tail moment (OTM) and the rate of comet cells were measured. BMHCs from AA patients were examined with comet assay before and after IST, and the results were compared with those from controls.</p><p><b>RESULTS</b>Comet parameters from 91 AA patients including TDNA, TL, TM, OTM comet cell percentage were (5.0 +/- 4.0)%, 11.3 +/- 7.2, 1.7 +/- 2.0, 1.5 +/- 1.4, (16.8 +/- 13.7)%, respectively, which were significantly higher than those from control group (P < 0.05). There were statistical differences between the comet parameters of severe AA (SAA)/non-SAA (NSAA) and those of control group (P < 0.05), but no difference in the comet parameters between SAA and NSAA patients (P > 0.05). The TDNA, TL, TM, OTM and comet cells percentage were (4.4 +/- 3.6)%, 10.4 +/- 7.5, 1.4 +/- 1.6, 1.3 +/- 1.4 and (20.2 +/- 21.2)%, respectively at 3 months after IST in 53 SAA patients and were (3.7 +/- 3.3)%, 10.0 +/- 7.2, 1.2 +/- 1.8, 1.1 +/- 1.3 and (18.5 +/- 19.0)% respectively at 6 months after IST in 30 SAA patients, being no statistical difference from those of 58 SAA patients before IST (P values were all > 0.05).</p><p><b>CONCLUSION</b>BMHCs of AA had inherent genetic instabilities which were not increased by recent IST. It indicated that there was no correlation between IST and the development of clonal hematologic disorders in AA.</p>

Bone marrow microvessel density and vascular endothelial growth factor expression in patients with aplastic anemia / 中华血液学杂志

<p><b>OBJECTIVE</b>To study the bone marrow microvessel density (MVD) and vascular endothelial growth factor (VEGF) expression and their clinical significance in patients with aplastic anemia (AA).</p><p><b>METHODS</b>Bone marrow biopsies in 51 newly diagnosed patients with AA were evaluated the MVD and VEGF expression by immunostaining with anti-factor VIII related antigen and VEGF monoclonal antibodies at regular time points after immunosuppressive therapy (IT).</p><p><b>RESULTS</b>The mean bone marrow MVD in AA group was 5.5 +/- 3.5, being significantly lower than that in normal control group (8.7 +/- 3.4, P < 0.05). MVDs of SAA and NSAA patients were 7.4 +/- 2.9 and 4.3 +/- 3.4, respectively, being significantly different (P < 0.01). The VEGF expression in AA group was significantly lower than that in control group [(6.7 +/- 8.4)% vs (14.7 +/- 6.1)%, P < 0.01], but there was no difference between SAA and NSAA. Bone marrow MVD and VEGF were significantly increased after IT in 22 responded AA patients.</p><p><b>CONCLUSION</b>Bone marrow MVD and VEGF expression are low in AA patients which may be one of pathophysiologic mechanisms of bone marrow failure in AA. Proangiogenic and ameliorating microcirculation agents together with IT might accelerate the recovery of hematopoiesis in AA patients.</p>

Natural killer-like T-cell lymphoma/leukemia--a case report and literature review / 中华血液学杂志

<p><b>OBJECTIVE</b>To identify the clinical and pathological features of natural killer-like T-cell lymphoma/leukemia.</p><p><b>METHODS</b>The characteristics of natural killer-like T-cell lymphoma/leukemia was discussed with report a new case and review of literatures.</p><p><b>RESULTS</b>A 16-year-old girl was referred to our hospital because of fever and disseminated cutaneous herpes and ulcer. Atypical lymphoid cells surrounded the dermal vessels with a CD3(+), CD8(+), CD4(-), CD5(-), CD10(-), CD19(-), CD57(-), CD56(+), perforin(+), granzyme B(+) immunophenotype and rearranged T-cell receptor-gamma gene implicated natural killer-like T cell origin. She was treated with prednisone and for several months. Then the patient developed progressive spleen enlargement with overt leukemia, which led to her eventual death.</p><p><b>CONCLUSIONS</b>Natural killer-like T-cell lymphoma/leukemia is a rare disease with distinctive clinical, histopathologic, and immuno phenotypic characteristics. Current treatment modalities are ineffective for most of the patients.</p>

Chronic idiopathic thrombocytopenic purpura in adult Chinese patients: a retrospective single-centered analysis of 1791 cases / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Adult chronic idiopathic thrombocytopenic purpura (ITP) is a common hematologic disease characterized by persistent thrombocytopenia. So far, there were only a few reports on adult Chinese patients with chronic ITP. This study aimed at defining the treatment outcome and prognostic factors for chronic ITP based on a large cohort of Chinese patients followed up for over 25 years at a single center.</p><p><b>METHODS</b>The medical records of 1791 patients aged 14 years or older who were diagnosed as having chronic ITP at our hospital from 1974 to 1999 were retrospectively analyzed.</p><p><b>RESULTS</b>The female-to-male ratio was 2:1, with a median age of 34 years (ranging from 14 to 80 years), median platelet count of 38 x 10(9)/L [range (1-99) x 10(9)/L], and median follow-up of 36 months (range 1-220 months). Steroids were used in 689 patients, among them 209 (30.3%) achieved complete remission (CR). A splenectomy was performed in 124 patients, and response to steroid pre-splenectomy was not available in 14 patients. The CR rate after a splenectomy was lower in steroid nonresponders (29 of 90, 32.2%) than in those who relapsed after successful steroid treatment (12 of 20, 60.0%) (P < 0.05). In comparison with patients negative for antinuclear antibody (ANA), those who were ANA positive had similar responses to steroids, but a significantly shorter remission period after a splenectomy (P < 0.01).</p><p><b>CONCLUSIONS</b>Adult Chinese chronic ITP patients can have long-term remission after steroid therapy and splenectomies. Primary steroid refractoriness is a prognostic factor predicting poor subsequent response to a splenectomy.</p>

The periodic change of environment factors in solid state fermentation and effect on microorganism fermentation / 生物工程学报

The periodic change of environment factors in air pressure oscillation solid state fermentation bioreactor was studied. Based this research the effect of the periodic environment stimulations on Penicillium decumbens JUA10 cultured in solid state substrate was researched too. The research results showed that in this bioreactor air temperature and relative humidity had large amplitude periodic change drived by air pressure oscillation. The changes had same frequency with the air pressure Oscillation and had amplitude that increased with the air pressure increased. When the press lower limit and upper limit were 0.0MPa and 0.2MPa respectively, pulsating period was 20 min, contrast to the period gather breath solid state fermentation, the air press pulsating SSF had a 2.29 times total CO2 production increase, 3.2 times enzyme activity increase and 1.04 times biomass increase. The data suggested air press pulsating stimulation not only increased biomass but also the metabolic activity.

Preliminary observation of the combination of arsenic trioxide and all-trans retinoic acid for the treatment of acute promyelocytic leukemia / 中华血液学杂志

<p><b>OBJECTIVE</b>To observe the efficacy and side effect of the all-trans retinoic acid (ATRA) and arsenic trioxide (As(2)O(3)) combination in acute promyelocytic leukemia (APL).</p><p><b>METHODS</b>Twenty APL patients were treated with the ATRA and As(2)O(3) combination, and 18 of them could be evaluated. The treatment protocol was as following: 10 mg As(2)O(3) (0.1% solution) in 500 ml 50 g/L glucose solution for intravenous drip over 4 to 6 hours once a day, ATRA was given 25 mg/m(2) every day.</p><p><b>RESULTS</b>Seventeen of the 18 patients achieved complete remission (CR), the CR rate was 94.4%. All 14 newly diagnosed patients and 3 of 4 relapsed patients achieved CR. No significant side effect was observed.</p><p><b>CONCLUSION</b>The As(2)O(3) and ATRA in the treatment of APL can obtain a higher CR rate and a shorter duration for achieving CR.</p>