Analysis of age-specific cytogenetic changes among 515 patients withacute myeloid leukemia / 中华医学遗传学杂志

OBJECTIVE@#To characterize cytogenetic changes and prognosis of patients with acute myeloid leukemia (AML) from different age groups.@*METHODS@#The karyotypes of 515 AML patients were analyzed by using short-term culture of bone marrow cells and R-banding technique. Combined with FAB typing and genetic testing, cytogenetic changes and prognosis of different age groups were analyzed.@*RESULTS@#The abnormal cloning rate was 54.6% among the 515 patients. The abnormal cloning rate and adverse risk karyotype proportion of those with myeloproliferative syndromes (MDS) and secondary AML were higher than those with de novo AML (P = 0.027; P<0.01). A significant difference was found in the number of structural abnormalities and proportion of favorable risk karyotypes among different age groups (P = 0.026; P = 0.004). And there was also a significant difference in the abnormal cloning rate between different FAB types (P<0.01). In those with non-acute promyelocytic leukemia (APL), the expression level of WT1 gene seemed to affect the prognosis. The survival rate of patients with karyotypes of adverse risk was lower than those with karyotypes of favorable risk (P = 0.015). The survival rate of the ≥60-year-old group was lower than the ≤30-year-old and 31 to 59-year-old groups (P<0.01, P<0.01).@*CONCLUSION@#The karyotypes of AML patients have different age distribution characteristics. The survival rate of ≥60-years-old group and karyotype of poor prognosis is low. Patients with MDS with secondary AML have a poor prognosis.

Detection of genomic abnormalities among 105 patients with chronic lymphocytic leukemia using fluorescence in situ hybridization / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To assess the value of fluorescence in situ hybridization (FISH) for the detection of genomic abnormalities among patients with chronic lymphocytic leukemia (CLL).</p><p><b>METHODS</b>Interphase FISH was performed on bone marrow samples derived from 105 patients with CLL at the time of diagnosis using probes for D13S319/13q14, ATM/11q22, P53/17p13 and CEP12. The abnormalities and prognostic factors were analyzed. Overall survival of the patients was calculated.</p><p><b>RESULTS</b>The FISH assay has detected genomic abnormalities in 81 (77.1%) of the patients, among which D13S319/13q14 deletion was the most common (49/105, 46.67%). 24(22.86%) patients had trisomy 12, 21(20.00%) had ATM/11q deletion, and 12(11.43%) had P53/17p deletion. A significant correlation was found between Binet staging and the detected abnormalities (< 0.05). With a median follow-up time of 10 months, 11 patients (10.5%) had died. Compared with those with P53 deletion, patients with 13q deletion showed a better overall survival. However, the overall survival did not significantly differ between patients with various genomic abnormalities (> 0.05).</p><p><b>CONCLUSION</b>FISH is capable of detecting common genomic aberrations among patients with newly diagnosed CLL. Deletion of D13S319/13q14 is the most common aberration in such patients. Genomic aberrations are significantly correlated with Binet staging but not the overall survival of CLL patients.</p>

Changes in aquaporin 4 expressions in the brain tissues of rats with streptococcus pneumoniae meningitis / 中华实用儿科临床杂志

Objective To investigate the expressions of aquaporin 4 (AQP4) in the bacterial meningitis in rats and to explore the molecular mechanism for brain edema caused by bacterial meningitis.Methods Totally 40 of 3-week-old-Sprague-Dawley healthy rats,body weight 60-80 g,male or female,were divided into a normal control group(n =10),and infection groups:24 hours after injection(n =10),48 hours after injection(n =10),and 5 days after injection(n =10).The expressions of AQP4 in the brain were detected by immunohistochemistry and Western blot methods respectively after 24 hours,48 hours,5 days of inoculation.Results Mortality rate:no rats in the control group and the infection group after 24 hours were dead.Two rats in the infection group after 48 hours and 4 rats in the infection group after 5 days were dead because of serious sickness,with the mortality rates 20％ and 40％,respectively.AQP4 expression was slightly positive under light microscope,and the positive cells mainly surrounded glial cells and blood vessels,while neurons were not dyed.Immunohistochemical staining showed that AQP4 expression in the model group increased with the severity of edema;compared with the control group,the AQP4 expression in the brain tissues increased in different periods after rats were infected,and the differences between groups were statistically significant (F--91.84,P ＜ 0.01).Western blot analysis showed that after the brain received streptococcus pneumoniae injection,expression of AQP4 began to increase in 24 hours after streptococcal injection,and reached to the peak in 48 hours,but decreased in 5 days,but the expression still remained higher than that of the normal control group.Each group had statistically significant difference(F =14.23,P ＜ 0.01).Conclusions Expression of AQP4 in the models with bacterial meningitis may increase initially and decrease later.It suggests that AQP4 plays a protective role during the development of infectious brain edema.

Clinical and cytogenetic study of chromosome 1 abnormality in myelodysplastic syndrome / 中华血液学杂志

<p><b>OBJECTIVE</b>To explore the incidence of chromosome 1 abnormality in myelodysplastic syndrome（MDS）to couple its association with clinical presentation and prognosis.</p><p><b>METHODS</b>R- band karyotype analyses were performed in 672 cases of MDS between 2010 and 2013. Clinical data of those with abnormal chromosome l were collected and then analyzed factors affecting the prognosis.</p><p><b>RESULTS</b>Of 672 cases of patients with MDS, chromosome 1 aberration［der（1）, dup（1）, －1 were most frequent］ were found in 41（6.1%）cases. 1q trisomy was found in 18/41（43.9%）cases, and the most common patterns were duplication of the long arm as well as unbalanced translocation with other chromosomes. Of 41 patients with chromosomal 1 abnormality, 32 cases were accompanied with other chromosomal aberration, usually involving 3 or more abnormal chromosomal karyotypes, e.g., chromosome 8, 7 abnormalities. According to IPSS-R scoring system, 19 patients were diagnosed with very high risk, 10 patients high risk, 10 patients intermediate risk and 2 patients low risk MDS. 9 patients transformed into acute leukemia with median transforming time of 7.18（0.56-54.28）months. Median survival of 36 cases after 2010 was 17.48（95% CI 14.38-20.58）months. There were significant differences on median survival between RAEB and non-RAEB groups（χ²=10.398, P=0.001）, and between with more than 3 chromosome abnormalities and with less than 3 groups（χ²=3.939, P=0.047）. RAEB was identified as an independent risk factor for the prognosis of MDS with chromosome 1 abnormality.</p><p><b>CONCLUSION</b>Chromosome 1 aberration was not rare in MDS. 1q trisomy was the most common abnormal karyotype in China, which often accompanied with other chromosomal abnormalities. The prognosis of MDS patients with chromosome 1 abnormality was poor, especially worse in those diagnosed with RAEB-1, RAEB-2 and with more than 3 chromosome abnormality. For patients whose percentage of bone marrow blasts less than 5%, the prognosis of patients with 1q trisomy was better than those without 1q trisomy. RAEB was identified as an independent risk factor for the prognosis of MDS with chromosome 1 abnormality.</p>

Expression level of SET gene in acute myeloid leukemia and its clinical significance / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate the expression level of SET gene in patients with acute myeloid leukemia (AML) and evaluate its significance.</p><p><b>METHODS</b>The expression level of SET gene in 141 de novo AML patients was determined by real time quantitative PCR (RQ-PCR), and its relationship with the clinical features and outcomes of these patients were analyzed.</p><p><b>RESULTS</b>SET gene transcript level was detected in 141 AML patients with the median expression level of 0.86(range 0.02-15.69). AML patients with higher SET gene expression had a higher level of white blood cell (WBC ≥ 100 × 10⁹/L) count than of lower SET gene expression ones (31.0% vs 11.4%, P=0.005). In the 136 patients who received treatment after diagnosis, higher SET gene expression group had lower complete remission rate (50.0%) than of lower expression cohort (73.5%) after two cycles of chemotherapy (P=0.005). Survival analysis showed that patients with higher SET gene expression had significantly shorter overall survival(OS) (10 months vs 22 months, P=0.001) and event-free survival (EFS) (2 months vs 14 months, P=0.005) than of lower SET gene expression ones. Multivariate COX regression analysis showed SET overexpression was an independent prognostic factor for OS. In the patients with the normal karyotype, higher SET expression group also had significantly shorter OS (12 months vs 35 months, P=0.010) and EFS (4 months vs 14 months, P=0.026) than of lower SET expression ones.</p><p><b>CONCLUSION</b>High expression of SET gene was associated with poor prognosis and might be a prognostic molecular marker of AML.</p>

Clinical significance of TET2 gene expression in 157 adult acute myeloid leukemia patients with normal cytogenetics / 中华血液学杂志

<p><b>OBJECTIVE</b>To explore the clinical significance of ten-eleven-translocation methylcytosine dioxygenase 2 (TET2) mRNA expression levels in adult acute myeloid leukemia patients with normal cytogenetics (CN-AML).</p><p><b>METHODS</b>Expression levels of TET2 mRNA were measured by real-time PCR in 157 adult CN-AML, and its clinical impact in CN-AML was evaluated as well.</p><p><b>RESULTS</b>TET2 gene expression levels from bone marrow mononuclear cells (BMMNCs) [7.29(3.41-9.99)] and CD34+ cells [6.02(5.64-6.54)] in CN-AML were significantly lower than those [BMMNCs: 8.13(6.68-9.04), P=0.026; CD34+ cells: 6.48(5.97-7.12), P=0.034] in healthy control. And TET2 mRNA level at diagnosis [7.32(6.11-8.41)] was obviously lower than that at complete remission [8.39(7.76-8.79), P<0.01]. CN-AML patients with lower levels of TET2 mRNA showed worse survival rate [(32.7±5.9)%] at 18-month than those with higher levels [(48.6±6.9)%, P=0.041]. In multivariate analysis, lower level of TET2 mRNA was an independent prognostic factor for OS [hazard ratio(HR)2.032, 95% confidence interval (CI)1.272-3.247, P=0.003] and event-free survival [HR 1.532, 95% CI 1.014-2.314, P=0.043].</p><p><b>CONCLUSION</b>The level of TET2 mRNA is significantly lower in patients with CN-AML and it is an independent negative prognostic factor. TET2 could be an important factor for the molecular-based risk stratification in CN-AML.</p>

Clinical and cytogenetic features of hematologic malignancies associated with acquired trisomy 21 / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate the association between trisomy 21 abnormalities and the clinical and cytogenetic features of hematologic malignancies.</p><p><b>METHODS</b>Chromosome preparations were made on bone marrow cells by using direct method and/or unstimulated short-term cultures. Karyotypes were analyzed by R-banding.</p><p><b>RESULTS</b>Thirteen patients (1.5%) with acute myeloid leukemia (AML) including 6 cases of M5b, 8 (2.2%) with acute lymphoblastic leukemia (ALL) and 4 cases with other hematologic malignancies had acquired trisomy 21, and in 13 patients it occurred as the sole cytogenetic abnormality. The remaining had combination with other abnormalities. The median survival for the 19 patients with trisomy 21 was 9 months.</p><p><b>CONCLUSION</b>M5b was the major type in AML with sole acquired trisomy 21.Trisomy 21 as the sole abnormality appeared to have a poor prognosis.</p>

Clinical and cytogenetics studies on acute myeloid leukemia with abnormality of chromosome 11 / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate the incidence of chromosome 11 abnormality in acute myeloid leukemia and its relationship with the clinical aspects and prognosis.</p><p><b>METHODS</b>Conventional cytogenetic analysis of R-band was used to detect the abnormalities of chromosome 11 in 356 acute myeloid leukemia patients.</p><p><b>RESULTS</b>Thirty-four out of 356 patients (9.55%) had abnormalities of chromosome 11, of which 20 (58.8%) involved in 11q23, 7 (19.9%) had translocations involving 11p15, 5 (14.7%) had-11, and the rest had other abnormalities such as +11, and t(11;14). The incidence of 11q23 involvement in M4 and M5 was higher than other subtypes of acute myeloid leukemia (AML). Ten cases with 11q23 abnormality had additional cytogenetic aberrations. In 30 cases treated with chemotherapy, 13 cases acquired complete remission (CR). The CR rate was lower than that of whole cases of acute myeloid leukemia(34.3% versus 64.0%). The CR rate of AML with 11q23 abnormality was lower than that of AML with normal karyotype (25% versus 55.6%). In other 10 patients with additional chromosome aberrations, the CR rate was lower than that of AML with 11q23 alone. In 7 patients with translocations at 11p15, only 3 patients acquired CR, and 2 patients relapsed early. Only 2 patients acquired CR in 5 patients with-11.</p><p><b>CONCLUSION</b>11q23 was a frequent aberration in chromosome 11 anomaly, which was often detected in M4 and M5. It might be associated with the pathogenesis of acute monolytic leukemia. The patients with chromosome 11 anomaly had poorer prognosis.</p>

Clinical presentations of smog disease / 中国基层医药

Objective To investigate the features of smog disease.Methods The clinical manifestations and inducements of smog disease patients were comprehensively analyzed by using clinical statistical methods.Results Smog disease mainly invaded young people.Smog disease was found mostly acute or subacute in onset.21 cases invaded internal carotid arterial system among these 30 patients,including infarction and cerebral hemorrhage;6 patients showed vertebral arterial signs,and 3 cases invaded both the two systems.Brain CT or MRI only showed the position of neurological disorder;The final diagnosis was made by DSA.Conclusion Smog disease could invade both the two systems of intracerebral artery,DSA is the best method to diagnose smog disease.

Effect of basic fibroblast growth factor on rat brain intracellular free calcium following focal ischemia-reperfusion injury / 中国组织工程研究

BACKGROUND: Basic fibroblast growth factor (bFGF) possesses multiple functions such as promoting neuronal survival and growth of cell processes in vitro and antagonizing the toxicity of excitatory amino acids,thereby playing import roles in functional recovery of the central nervous system (CNS). But whether bFGF offers neuroprotection on ischemic brain tissues by modulating intracellular free calcium content remains unknown.OBJECTIVE: To explore the effect of bFGF on intracellular free Ca2+ in the neural cells in the event of focal cerebral ischemia-reperfusion (IR)injury.DESIGN: Randomized controlled study.SETTING: Department of Neurology of Second Hospital Affiliated to Zhengzhou University.MATERIALS: This study was conducted in the Laboratory of the Department of Neurology, Second Hospital Affiliated to Zhengzhou University between August and December 2003. Totally 24 SD were randomized into sham operation group, ischemic group, IR group and bFGF exposure group with 8 rats in each group.METHODS: Middle cerebral artery occlusion (MCAO) model was established in rats in IR group and bFGF exposure group by inducing arterial thrombosis with thread, which was not preformed in rats in the sham operation group. Rats in bFGF exposure group received intraperitoneal injection of 10 μg/kg bFGF immediately after ischemia,which was replaced by the same volume of physical saline in the other two groups. Free Ca2+ in brain cells was detected at 24 hours of IR.MAIN OUTCOME MEASURES: Free Ca2+ in the brain cells at 24hours of IR.RESULTS: All the 24 rats survived the experiment. Free Ca2+ in IR group was significantly higher than that of the sham operation group [(673.46±18.44) vs (224.71±10.58) nmol/L, F=1 329.06, P ＜ 0.01], and also significantly higher in bFGF exposure group [(378.37±21.08) nmol/L,F=1 329.06, P ＜ 0.01].CONCLUSION: Intracellular free calcium can be obviously depressed by bFGF following IR injury, which benefits cell membrane stability and help prevent intracellular Ca2+ overload.

Platelet activation and brain protection of protein hydrolysate injection for patients with acute stroke / 中国组织工程研究

BACKGROUND: The blood levels of specific markers of platelet activation, such as platelet granule membrane protein (GMP-140) and tumor necrosis factor alpha (TNF-α) are very low in healthy individuals, while the plasma levels of them in patients with cerebral infarction increase. Is the protection of brain hydrolysate injection correlated with the phenomenon?OBJECTIVE: In this study, the plasma levels of GMP-140 and TNF-α in patients with acute stroke were measured, the brain protection of brain protein hydrolysate injection on patients with ischemic stroke were investigated, and were compared with the therapeutic effect of compound danshen injection.DESIGN: It was designed for case study.SETTING: This study was conducted at the Medical Department of the General Hospital of Pingdingshan Coal Co. Ltd and the Neurology Department of the Second Hospital Affiliated to Zhengzhou University.PARTICIPANTS: From January 2001 to October 2003, 144 inpatients with hypertension and acute stroke in the Medicine Department of the General Hospital of Pingdingshan Coal Co. Ltd were selected and divided into 2 groups, as experiment group containing 72 cases, 47 males and 25females, with an age from 42 to 90 and in average of (69±11) years old and control group containing 72 cases, 49 males and 23 females, with an age from 37 to 85 and in average of (68±10) years old.METHODS: All the patients in these two groups underwent oxygen inhalation therapy, antihypeetensive therapy, dehydration therapy and anticoagulation therapy. Patients in control group were coadministered 500 mL compound salvia miltiorrhiza injection QD once a day, with a 14-day course of therapy. Patients in experiment group were treated with 500 mL compound salvia miltiorrhiza injection QD and 20 mL protein hydrolysate European stroke scale (ESS), from 0 (worst possible health status) to 100(best possible health status), were used to evaluate the recovery status of (from 24 hours to 72 hours) and 3 weeks post-treatment, 5 mL blood samples were obtained from antecubital veins, then plasma levels of GMP-140and TNF-α were quantified using an RIA (radioimmunoassay) and the changes in neural function before and after brain protein hydrolysate injection were evaluated.MAIN OUTCOME MEASURES: Before treatment and at 3 weeks postwere quantified using an RIA.RESULTS: All the 144 patients entered the statistical analysis procedure.ESS were significantly higher than the pre-treatment scores [Experiment groups: 79.95±18.64 and 59.65±19.87; Control group: (74.66±15.88) and (61.25±18.68), (t=2.678-4.351, P ＜ 0.01). The post-treatment scores of ESS in experiment group were higher than those in control group (t=2.016-2.158,groups, the post-treatment outcomes were significantly lower than the pre-treatment outcomes [Experiment group: (22.12±9.52) μg/L and (50.41±22.35) μg/L, (1.05±0.24) μg/L and (1.62±0.50) μg/L; Control group: (26.66±8.22) μg/L and (48.63±21.54) μg/L, (1.35±0.44) μg/L and (1.66±0.48) μg/L; (t=2.678-4.351, P ＜ 0.001)]. And the post-treatment levels of the two markers were lower in experiment group than those in control group (t=2.016-2.158, P ＜ 0.05).CONCLUSION: Brain protein hydrolysate injection can significantly decrease the plasma levels of GMP-140 and TNF-α in patients with acute stroke, and it is capable of increasing the ESS scores and improving the impaired neural functions greatly.

Preparation and characterization of monoclonal antibody against human telomeric repeat binding factor 1 / 中华血液学杂志

<p><b>OBJECTIVE</b>To prepare a monoclonal antibody against human telomeric repeat binding factor 1 (TRF1) protein and explore its biological characteristics.</p><p><b>METHODS</b>BALB/c mice were immunized with GST-TRF1(33-277) fusion protein for the preparation of monoclonal antibody by hybridoma technique. The obtained antibody was used for clinical assay by Western-blot and immunohistochemical staining.</p><p><b>RESULTS</b>One strain of hybridoma was obtained. It was confirmed by Western-blot that the antibody specifically recognized the 60 kD TRF1 protein. Immunohistochemical staining of the antibody showed that TRF1 protein located in the cytoplasm of epithelial cells and bone marrow cells.</p><p><b>CONCLUSION</b>A TRF1 monoclonal antibody, with high specificity was developed. It is useful for detection of TRF1 protein in tissue specimens.</p>