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1.
Chinese Journal of Hematology ; (12): 728-736, 2023.
Artigo em Chinês | WPRIM | ID: wpr-1012221

RESUMO

Objective: To analyze and compare therapy responses, outcomes, and incidence of severe hematologic adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia (CML) . Methods: Data of patients with chronic phase CML diagnosed between January 2006 and November 2022 from 76 centers, aged ≥18 years, and received initial flumatinib or imatinib therapy within 6 months after diagnosis in China were retrospectively interrogated. Propensity score matching (PSM) analysis was performed to reduce the bias of the initial TKI selection, and the therapy responses and outcomes of patients receiving initial flumatinib or imatinib therapy were compared. Results: A total of 4 833 adult patients with CML receiving initial imatinib (n=4 380) or flumatinib (n=453) therapy were included in the study. In the imatinib cohort, the median follow-up time was 54 [interquartile range (IQR), 31-85] months, and the 7-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.2%, 88.4%, 78.3%, and 63.0%, respectively. The 7-year FFS, PFS, and OS rates were 71.8%, 93.0%, and 96.9%, respectively. With the median follow-up of 18 (IQR, 13-25) months in the flumatinib cohort, the 2-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.4%, 86.5%, 58.4%, and 46.6%, respectively. The 2-year FFS, PFS, and OS rates were 80.1%, 95.0%, and 99.5%, respectively. The PSM analysis indicated that patients receiving initial flumatinib therapy had significantly higher cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) and higher probabilities of FFS than those receiving the initial imatinib therapy (all P<0.001), whereas the PFS (P=0.230) and OS (P=0.268) were comparable between the two cohorts. The incidence of severe hematologic adverse events (grade≥Ⅲ) was comparable in the two cohorts. Conclusion: Patients receiving initial flumatinib therapy had higher cumulative incidences of therapy responses and higher probability of FFS than those receiving initial imatinib therapy, whereas the incidence of severe hematologic adverse events was comparable between the two cohorts.


Assuntos
Adulto , Humanos , Adolescente , Mesilato de Imatinib/efeitos adversos , Incidência , Antineoplásicos/efeitos adversos , Estudos Retrospectivos , Pirimidinas/efeitos adversos , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Resultado do Tratamento , Benzamidas/efeitos adversos , Leucemia Mieloide de Fase Crônica/tratamento farmacológico , Aminopiridinas/uso terapêutico , Inibidores de Proteínas Quinases/uso terapêutico
2.
Journal of Experimental Hematology ; (6): 1647-1656, 2023.
Artigo em Chinês | WPRIM | ID: wpr-1010018

RESUMO

OBJECTIVE@#To establish a new digital polymerase chain reaction (dPCR) system for the detection of BCR-ABL fusion gene in patients with chronic myeloid leukemia (CML), and explore its analytical performance and clinical applicability in the detection of BCR-ABLp190/210/230.@*METHODS@#A new dPCR system for detecting BCR-ABLp190/210/230 was successfully developed, and its sensitivity difference with qPCR and improvement of drug side effects in patients with CML during drug reduction or withdrawal were compared.@*RESULTS@#Among 176 samples, qPCR and dPCR showed high consistency in the sensitivity of detecting BCR-ABL (82.39%), and the positive rate of dPCR was about 5 times higher that of qPCR (20.45% vs 3.98%). During follow-up, blood routine (25% vs 10%), kidney/liver/stomach (25% vs 20%) and cardiac function (10% vs 0) were significantly improved after drug reduction or withdrawal in patients with initial dPCR negative compared with before drug reduction or withdrawal.@*CONCLUSIONS@#This new dPCR detection system can be applied to the detection of BCR-ABLp190/210/230. It has better consistency and higher positive detection rate than qPCR. Drug withdrawal or dose reduction guided by dPCR has a certain effect on improving drug side effects.


Assuntos
Humanos , Proteínas de Fusão bcr-abl/genética , Leucemia Mielogênica Crônica BCR-ABL Positiva/diagnóstico , Reação em Cadeia da Polimerase , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Reação em Cadeia da Polimerase Via Transcriptase Reversa
3.
Chinese Acupuncture & Moxibustion ; (12): 263-266, 2019.
Artigo em Chinês | WPRIM | ID: wpr-775938

RESUMO

OBJECTIVE@#To explore the clinical effect of rapid massage at Shuidao (ST 28) to prevent puerpera from postpartum urinary retention.@*METHODS@#A total of 200 puerpera giving birth through vagina were enrolled and divided into an observation group and a control group according to the random number table method, 100 cases in each group. In the observation group, rapid massage at Shuidao (ST 28) was applied. In the control group,there was no intervention and urinated naturally. The traditional Chinese medicine syndrome scale was used to evaluate poor sense of urination, and record puerpera with or without postpartum urinary retention, the poor sense of first urination, the first time of urination, the amount of first urination and postpartum hemorrhage.@*RESULTS@#The poor sense of first urination in the observation group was significantly lower than that in the control (<0.001), the first time of urination in the observation group was significantly earlier than that in the control group (<0.001), the amount of first urination in the observation group was significantly more than that in the control group (<0.001), the observation group was superior to the control group to prevent postpartum urinary retention (<0.05).@*CONCLUSION@#Rapid massage at Shuidao (ST 28) can reduce the poor sense of first urination, significantly advance the time of spontaneous urination, significantly increase the amount of first urination and effectively prevent postpartum urinary retention.


Assuntos
Feminino , Humanos , Gravidez , Pontos de Acupuntura , Massagem , Período Pós-Parto , Retenção Urinária , Terapêutica , Micção
4.
Journal of Experimental Hematology ; (6): 1300-1306, 2017.
Artigo em Chinês | WPRIM | ID: wpr-301732

RESUMO

<p><b>OBJECTIVE</b>To study the expression of stromal cell derived factor-1α (SDF-1α) receptor CXCR7 in acute monocytic leukemia (AML-M5), and its effects on proliferation, apoptosis, invasion of acute monocytic leukemia cell line THP-1.</p><p><b>METHODS</b>CXCR7 protein and mRNA expression levels in THP-1 cells and peripheral blood mononuclear cells (PBMNC) from the newly diagnosed AML-M5 patients and normal individuals were detected by flow cytometry, Western blot and RT-PCR respectively. CCK8, Annexin V/PI double staining and Transwell assay were used to observe the effects of CXCR7 on the proliferation, apoptosis, and invasion of THP-1 cells in vitro.</p><p><b>RESULTS</b>The expression of CXCR7 on immature cell surface of the newly diagnosed AML-M5 patients was significantly higher than that in the control group (P<0.05). CXCR7 was also highly expressed on THP-1 cells surface. The CXCR7 protein and mRNA levels in THP-1 cells and PBMNC of AML-M5 patients were significantly higher than those in the control group (P<0.05). The THP-1 cell proliferation activity was higher in SDF-1α-treated group, but this activity could be inhibited by CXCR7 antibody (P<0.01). CXCR7 antibody did not affect THP-1 cell apoptosis (P>0.05). CXCR7 antibody could inhibit SDF-1α -induced THP-1 cell invasiveness (P<0.01).</p><p><b>CONCLUSION</b>CXCR7 highly expresses in AML-M5 patients and THP-1 cells, and involves in cell proliferation and invasion. The blocking CXCR7 expression can reduce the risk of AML-M5 cell infiltration.</p>

5.
International Journal of Traditional Chinese Medicine ; (6): 430-434, 2017.
Artigo em Chinês | WPRIM | ID: wpr-513068

RESUMO

Objective To study the effect of Corylin on A375 cells melanin synthesis,and explore its mechanism.Methods The cells were randomly divided into the control group, the estradiol group, and corylin group including 10-3μmol/L, 10-2μmol/L, 10-1μmol/L, 1μmol/L, 10μmol/L, 100μmol/L. Estradiol estradiol intervention group were given 10-3 mol/L. Corylin group (10-3μmol/L, 10-2μmol/L, 10-1μmol/L, 1μmol/L, 10μmol/L,100μmol/L) were given 10-3μmol/L, 10-2μmol/L, 10-1μmol/L, 1μmol/L, 10μmol/L, 100μmol/L corylin intervention. The activity of proliferation were detected by MTT, NaOH method, dopa oxidation , both melanin content and tyrosinase activity (tyrosinase, TYR). TYR, yrosinase related protein (tyrosinase related protein, TRP)-1 and TRP-2 expression levels of mRNA were determined by RT-PCR.Results Compared with the control group, 10, 100μmol/L of Corylin group cell proliferation rate significantly decreased (P<0.01). The 1μmol/L, 10-1μmol/L, 10-2μmol/L of Corylin group cell melanin content, TYR significantly decreased (P<0.01 or P<0.05). The 1μmol/L corylin group TYR (0.303 ± 0.003vs. 0.628 ± 0.012), TRP-1 (0.313 ± 0.008 vs. 0.677 ± 0.022), TRP-2 (0.456 ± 0.028vs. 0.687 ± 0.020) mRNA expression level significantly decrease (P<0.01).Conclusions The results showed that Corylin could inhibit melanin synthesis, which worked probably through inhibiting the activity of TYR and cutting the mRNA expressions of TYR,TRP-1/2.

6.
Journal of Experimental Hematology ; (6): 427-432, 2016.
Artigo em Chinês | WPRIM | ID: wpr-360073

RESUMO

<p><b>OBJECTIVE</b>To investigate the predictive value of neutrophil/lymphocyte ratio (NLR) and platelet/lymphocyte ratio (PLR) for the patients with diffuse large B-cell lymphoma (DLBCL).</p><p><b>METHODS</b>The clinical data of 57 DLBCL patients admitted in the First Affiliated hospital of Anhui Medical University were analyzed retrospectively. According to ROC curve, the cut-off value for NLR and PLR was deterimined, and the patients were divided into high and low NLR/PLR groups before first chamotherapy. Then the relation of NLR and PLR with overall survival (OS) and progression-free survival (PFS) was analyzed by univariate and multivariate COX regression.</p><p><b>RESULTS</b>The optimal cut-off value for NLR and PLR was 2.915 and 270.27, respectively. NLR at the diagnosis was found to be an independent predictor for OS and PFS by univariate and multivariate analysis, while the PLR was an independent predictor for PFS, but did not affect the OS.</p><p><b>CONCLUSION</b>NLR and PLR may provide additional prognostic information for DLBCL patients.</p>


Assuntos
Humanos , Plaquetas , Biologia Celular , Intervalo Livre de Doença , Contagem de Linfócitos , Linfócitos , Biologia Celular , Linfoma Difuso de Grandes Células B , Diagnóstico , Análise Multivariada , Neutrófilos , Biologia Celular , Prognóstico , Estudos Retrospectivos
7.
Journal of Experimental Hematology ; (6): 1380-1385, 2015.
Artigo em Chinês | WPRIM | ID: wpr-274031

RESUMO

<p><b>OBJECTIVE</b>To investigate the influence of divalent cation chelator EDTA and heparin sodium on the detection of ITP platelet-specific autoantibodies by the modified monoclonal antibody immobilization of platelet antigen assay (MAIPA) and to explore the relationship between types of platelet specific autoantibodies and glucocorticoid efficacy.</p><p><b>METHODS</b>The samples were obtained from EDTA- and heparin- anticoagulant ITP patients, respectively, so as to detect the platelet-specific autoantibodies (GPIIb/IIIa and GPIbα) in 140 ITP samples by modified MAIPA, then the differences between these two methods were compared.</p><p><b>RESULTS</b>Out of 140 cases in EDTA group, 55 cases were positive for GPIIb/IIIa, while 76 cases in heparin group were positive for GPIIb/IIIa, 42 cases in both group were repeatable; among them 13 cases were positive in EDTA group and negative in heparin group, while 34 cases were positive in heparin group and negative in EDTA group, there was significant difference between them (x (2) = 9.38, P < 0.05), 62 cases in 140 cases of EDTA group were positive for GPIba, while 51 cases in heparin group were positive for GPIba, 42 cases in both group were repeatabe; among them 20 cases were positive in EDTA group and negative in heparin group, while 9 cases were positive in heparin group and negative in EDTA group, there was no significant difference between them (x (2) = 3.44, P > 0.05). A total of 320 cases received a standard glucocorticoid treatment, out of them 143 cases were positive for GPIbα with effective rate 39.9%, 177 cases were negative for GPIbα with effective rate 79.7%, there was statisticalty significant difference between them (x (2) = 53.115, P < 0.05).</p><p><b>CONCLUSION</b>EDTA anticoagulant (a divalent cation chelator) has a significant influence on detection of ITP platelet-specific autoantibodies (GPIIb/IIIa) by a modified MAIPA method and the GPIbα antibody positive may be one of the important factors that results in un-sensitivity of ITP patients to glucocorticoid treatment.</p>


Assuntos
Humanos , Anticorpos Monoclonais , Anticoagulantes , Usos Terapêuticos , Antígenos de Plaquetas Humanas , Autoanticorpos , Sangue , Plaquetas , Alergia e Imunologia , Fibrinolíticos , Glucocorticoides , Usos Terapêuticos , Heparina , Complexo Glicoproteico GPIIb-IIIa de Plaquetas , Púrpura Trombocitopênica Idiopática , Sangue , Alergia e Imunologia
8.
Journal of Experimental Hematology ; (6): 460-464, 2015.
Artigo em Chinês | WPRIM | ID: wpr-259565

RESUMO

<p><b>OBJECTIVE</b>To detect desialylation of platelets in primary immune thrombocytopenia(ITP) patients with FITC-labelled ECL and RCA-1, and compare the correlation of the desialylation level and the efficacy of first-line therapy for ITP.</p><p><b>METHODS</b>Before treatment, 48 ITP patients were selected and their levels of ECL and RCA-1 were detected with flow cytometry.</p><p><b>RESULTS</b>The desialylation level in the different efficacy groups by using the first-line therapy of corticosteroids and (or) intravenous immunoglobulin G (IVIG) had a statistically significant difference (P<0.05). The correlation analysis showed negative relation of the therapeutic efficacy with desialylation level, that is to say, the more high of desialylation level, the more poor therapeutic efficacy of the first-line therapy.</p><p><b>CONCLUSION</b>The desialylation level of platelets in ITP patients is related with the first-line therapeutic efficacy, the efficacy for patients with high desialylation level is poor, suggesting that the FcR-independent pathway exists in clearance of platelets in ITP patients. Therefore, the desialylation level of platelets may suggest the first-line therapeutic efficacy for ITP patients to a certain degree, and may be used as a potential target for the treatment of refractory ITP.</p>


Assuntos
Humanos , Corticosteroides , Plaquetas , Citometria de Fluxo , Imunoglobulina G , Imunoglobulinas Intravenosas , Púrpura Trombocitopênica Idiopática
9.
Chinese Journal of Hematology ; (12): 183-186, 2012.
Artigo em Chinês | WPRIM | ID: wpr-345903

RESUMO

<p><b>OBJECTIVE</b>To evaluate the relationship between plasma trough level of imatinib and clinical outcomes in Chinese CML patients.</p><p><b>METHODS</b>Plasma trough levels in 416 CML patients who received imatinib orally in six general hospitals were assessed. The correlations of imatinib plasma trough level with baseline characteristics including age, weight and BSA, and clinical response were evaluated.</p><p><b>RESULTS</b>(1) Effects of age, body weight and BSA on imatinib plasma trough levels were not to be clinically significant. (2) Median imatinib plasma trough levels was 1271 (109-4329). Imatinib plasma trough level was related to dose of imatinib administration. Plasma trough levels at imatinib of dose < 400, 400 and > 400 mg were (969 ± 585), (1341 ± 595) and (1740 ± 748) µg/L (P < 0.01), respectively. (3) There was no statistic difference in imatinib plasma trough level with complete cytogenetic response [CCyR (1337 ± 571) µg/L vs no CCyR (1354 ± 689) µg/L, P = 0.255]. (4) Imatinib plasma trough level might be important for a good clinical response in some CML patients.</p><p><b>CONCLUSION</b>There was a large interpatient variability in imatinib plasma concentration in Chinese CML patients. No correlation of imatinib plasma trough level with CCyR was observed. However, higher doses of imatinib were shown to attain greater trough plasma concentration, suggesting that imatinib plasma trough level might be important for a good clinical response in some CML patients.</p>


Assuntos
Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Povo Asiático , Benzamidas , Sangue , Usos Terapêuticos , Mesilato de Imatinib , Leucemia Mielogênica Crônica BCR-ABL Positiva , Sangue , Tratamento Farmacológico , Piperazinas , Sangue , Usos Terapêuticos , Pirimidinas , Sangue , Usos Terapêuticos , Resultado do Tratamento
10.
Chinese Journal of Medical Genetics ; (6): 28-33, 2012.
Artigo em Chinês | WPRIM | ID: wpr-295539

RESUMO

<p><b>OBJECTIVE</b>To explore the feasibility of applying autosomal single nucleotide polymorphisms (SNPs) on parentage testing.</p><p><b>METHODS</b>All SNP genotyping results of HapMap (r27) were downloaded from the website. With self-made computer programs, SNPs were extracted when their minor allele frequency (MAF) were ≥ 0.30 among all of the 11 HapMap populations. Ninety-six SNPs were chosen and integrated into the Illumina Goldengate bead arrays on the condition that no linkage disequilibrium was found between them. Three father-child-mother trios (9 samples in total) were tested with the arrays. Cumulative paternity index (CPI) was then calculated and compared with genotyping results using 15 short tandem repeats (STRs)(Identifiler(TM)).</p><p><b>RESULTS</b>Family 1 was found to have nine SNPs or seven STRs that did not conform to the Mendelian laws, Family 2 had 13 such SNPs or seven STRs, and Family 3 only had one such SNP but no STR. For Family 3, when all of the 96 SNPs were used in combine, the CPI was 1207, which had contrasted with the CPI by the 15 STRs, i.e., 355 869.</p><p><b>CONCLUSION</b>When applied to paternity testing, the paternity exclusion (PE) value for a SNP is usually less than 1/3 of that of a STR. The proportion of SNPs not comforming to the Mendelian laws for the tested SNPs may not be as high as that of inconsistent STRs over all tested STRs. Because of the low mutation rate of a SNP, the CPI will be greatly reduced even if one SNP did not conform to the Mendelian laws. Therefore, highly accurate testing methods are required to reduce artificial errors when applying SNPs for paternity testing.</p>


Assuntos
Feminino , Humanos , Masculino , Pai , Testes Genéticos , Métodos , Genótipo , Projeto HapMap , Mães , Paternidade , Polimorfismo de Nucleotídeo Único , Genética
11.
Chinese Medical Journal ; (24): 2248-2253, 2011.
Artigo em Inglês | WPRIM | ID: wpr-338562

RESUMO

<p><b>BACKGROUND</b>The interleukin-1 (IL-1) receptor-associated kinase 1 (IRAK1) is believed to play an important role in the pathogenesis of sepsis. Recent studies have suggested that the IRAK1 functional genetic variant could affect the severity of sepsis in Caucasians. In this report, we have investigated whether polymorphisms at the IRAK1 gene are associated with the susceptibility to and severity of sepsis among the Chinese population.</p><p><b>METHODS</b>Haplotype-tagging single nucleotide polymorphisms (htSNPs) were selected from the HapMap database. They were genotyped in 255 patients with sepsis and 260 control subjects by PCR/restriction fragment length polymorphism (RFLP) analysis. The association between the selected htSNPs and the susceptibility to and severity of sepsis were estimated by Logistic regression with adjustments for age, sex, smoking, drinking, chronic disease status, Acute Physiology and Chronic Health Evaluation (APACHE) II score and primary diseases.</p><p><b>RESULTS</b>rs1059702 was selected to represent the six linked htSNPs for IRAK1. Genotype frequencies of the htSNPs were in Hardy-Weinberg equilibrium for females, as were allele frequencies for both sex groups. Associations were observed in females between the htSNPs C/C genotype and increased susceptibility to sepsis (odds ratio (OR), 5.46; 95% confidence interval (CI), 1.12 - 26.67; P = 0.018), and such associations were also observed between the IRAK1 variant haplotype (CC/C-allele) and increased susceptibility to sepsis (OR, 1.68; 95% CI, 1.05 - 2.70; P = 0.031) when compared with the T/T + T/C genotype and the wild-type haplotype (TC + TT/T-allele). In the multiple organ dysfunction syndrome (MODS) subgroup, the variant haplotype was also associated with increased severity of sepsis (OR, 2.37; 95% CI, 1.13 - 4.94; P = 0.02) when compared with the wild haplotype. This association was not significant in male patients.</p><p><b>CONCLUSIONS</b>The functional polymorphism in exon 5 and the variant haplotype of IRAK1 gene mediate susceptibility to and severity of sepsis. IRAK1 might be a genetic risk factor for the occurrence and development of sepsis in the Chinese population.</p>


Assuntos
Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Povo Asiático , Éxons , Genética , Predisposição Genética para Doença , Genética , Genótipo , Haplótipos , Genética , Quinases Associadas a Receptores de Interleucina-1 , Genética , Polimorfismo de Fragmento de Restrição , Genética , Polimorfismo de Nucleotídeo Único , Genética , Sepse , Genética
12.
Chinese Journal of Oncology ; (12): 345-348, 2011.
Artigo em Chinês | WPRIM | ID: wpr-303300

RESUMO

<p><b>OBJECTIVE</b>To investigate the effect of total astragalosides (TA) on proliferation and apoptosis in human leukemia NB4 cells in vitro.</p><p><b>METHODS</b>The NB4 cells were treated with TA at different concentrations for 48 h in culture. Growth inhibition rates were measured by CCK-8 method. Flow cytometry was used to explore the cell apoptosis and the activity of NF-κB and Akt during apoptosis.</p><p><b>RESULTS</b>TA at different concentrations (200, 400, 600, 800 mg/L) inhibited proliferation of NB4 cells in a dose-dependent manner (P < 0.05), and the inhibitory rates of TA on NB4 cells were (14.54 ± 3.20)%, (24.79 ± 3.98)%, (57.28 ± 4.71)% and (88.28 ± 4.65)%, respectively. In terms of the induction of apoptosis, there was a significant difference between the TA group and blank control [(1.80 ± 1.24)%, P < 0.05]. At TA doses of 200, 400 and 600 mg/L, the apoptotic rates of NB4 cells were (10.03 ± 3.31)%, (14.87 ± 3.65)%, (23.45 ± 1.90)%, respectively. Besides, TA induced apoptosis of NB4 cells in a dose-dependent manner in the groups of 200 mg/L, 400 mg/L, 600 mg/L (P < 0.05). But there was no significant difference in apoptotic rates between the groups of 800 mg/L and 600 mg/L [(23.45 ± 1.90)%, P > 0.05]. In the group of 800 mg/L, the necrotic cells increased highly and the necrotic rate reached (45.65 ± 3.16)%. After TA treatment of NB4 cells at different concentrations (200, 400, 600 mg/L), the expression of NF-κB protein was significantly decreased compared with that of the blank control (9.79 ± 0.95, P < 0.05), while Akt protein was not significantly decreased (P > 0.05).</p><p><b>CONCLUSION</b>TA can inhibit the growth of NB4 cells and induce apoptosis in NB4 cells through an Akt-independent NF-κB signaling pathway.</p>


Assuntos
Humanos , Antineoplásicos Fitogênicos , Farmacologia , Apoptose , Astragalus propinquus , Química , Linhagem Celular Tumoral , Proliferação de Células , Medicamentos de Ervas Chinesas , Farmacologia , Leucemia Promielocítica Aguda , Metabolismo , Patologia , NF-kappa B , Metabolismo , Proteínas Proto-Oncogênicas c-akt , Metabolismo , Saponinas , Farmacologia
13.
Journal of Experimental Hematology ; (6): 49-53, 2010.
Artigo em Chinês | WPRIM | ID: wpr-328574

RESUMO

This study was purposed to evaluate ABL tyrosine kinase point mutations in imatinib-treated chronic myeloid leukemia (CML) patients and their clinical significance. 51 bone marrow samples from 28 imatinib-resistant patients and 10 newly diagnosed CML patients were collected. ABL kinase domain of bcr-abl allele was amplified by nested reverse transcription-polymerase chain reaction, followed by purifying, directly sequencing and sequence homology analysis of amplified products in order to determine the existence and type of point mutation. The results showed that the point mutations were found in 12 of 38 patients, and all the 12 ones progressed to advanced disease or death. 2 patients showed Met351Thr mutation, 7 patients showed Glu252His, 2 patients showed Glu279Lys, the other types were Glu255Val and Glu355Gly, each of which was tested in one patient. The incidence of the point mutation was 17.6%, 45.5% and 44.4% in chronic, accelerated and blast phase respectively. The incidences of point mutation in hematologically and genetically resistant patients were 50% (5/10) and 44.4% (8/18), and the 95% confidence interval (CI) was 12.3% - 87.7% and 19% - 69.9% respectively. It is concluded that ABL kinase point mutation is an important mechanism of imatinib resistance, monitoring the ABL kinase domain point mutation is helpful to estimating the prognosis and adjusting the therapeutic strategy.


Assuntos
Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Benzamidas , Mesilato de Imatinib , Leucemia Mielogênica Crônica BCR-ABL Positiva , Tratamento Farmacológico , Genética , Piperazinas , Usos Terapêuticos , Mutação Puntual , Proteínas Tirosina Quinases , Genética , Pirimidinas , Usos Terapêuticos , Resultado do Tratamento
14.
Chinese Journal of Hematology ; (12): 590-593, 2010.
Artigo em Chinês | WPRIM | ID: wpr-353611

RESUMO

<p><b>OBJECTIVE</b>To investigate the frequency and clinical implication of JAK2 mutation in patients with myeloproliferative neoplasm(MPN)and the correlation between the mutation and thrombosis.</p><p><b>METHODS</b>The clinical and laboratory data of 107 MPN patients was retrospectively analyzed. JAK2 mutation were detected with allele-specific polymerase chain reaction (AS-PCR) and sequencing. The significance of the mutation in disease diagnosis and molecular pathogenesis and the correlation between the mutation and thrombosis was analysed.</p><p><b>RESULTS</b>JAK2 mutation was detected in 71 (66.4%) and thrombosis in 34 (31.8%) of the 107 MPN patients. Thrombosis occurred in 34.8% (16/46) of polycythemia vera (PV), 32.6% (14/43) of essential thrombocythemia (ET), and 22.2% (4/18) of primany myelofibrosis (PMF) patients. The difference among the 3 groups was not significant (χ(2) = 0.96, P > 0.05). The frequency of thrombosis in JAK2(+) MPN patients (82.4%, 28/34) was higher than that in JAK2(-) MPN patients (17.6%, 6/34) (χ(2) = 5.71, P < 0.05). The frequency of thrombosis in MPN patients > 60 years was higher (41.5%, 27/65) than that in patients < 60 years (16.7%, 7/42) (χ(2) = 7.28, P < 0.01).</p><p><b>CONCLUSION</b>JAK2 V617F mutation occurs in significant percentage of Chinese patients with MPN. Patients with JAK2 mutation and older age are more succeptible to thrombosis. JAK2 mutation screening in patients with unknown thrombosis is helpful to reveal the underlying latent-MPN.</p>


Assuntos
Humanos , Mutação , Transtornos Mieloproliferativos , Genética , Neoplasias , Trombocitemia Essencial , Genética , Trombose
15.
Acta Pharmaceutica Sinica ; (12): 1415-1420, 2010.
Artigo em Chinês | WPRIM | ID: wpr-353346

RESUMO

Four impurities were isolated from raw material of clindamycin phosphate (CP), and their structures have been determined. LC-MS was used to determine the molecular weights of the impurities in the raw material of CP. Reversed-phase preparative HPLC was used to prepare them, and their chemical structures were identified by HR-MS and NMR. The four unknown impurities were determined as clindamycin-B-phosphate (1), clindamycin-2,4-diphosphate (2), 3',6'-dehydro clindamycin phosphate (3), epi-clindamycin phosphate (4). Impurity 1 has been included in BP and EP, while 2, 3 and 4 have not. The impurities 2, 3, 4 are first separated from raw material of CP.


Assuntos
Antibacterianos , Química , Cromatografia Líquida de Alta Pressão , Cromatografia Líquida , Clindamicina , Química , Contaminação de Medicamentos , Estrutura Molecular , Peso Molecular , Espectrometria de Massas por Ionização por Electrospray
16.
Chinese Journal of Hepatology ; (12): 125-128, 2008.
Artigo em Chinês | WPRIM | ID: wpr-277587

RESUMO

<p><b>OBJECTIVE</b>To observe the effect of calorie restriction on the high fat diet rats mRNA expressions of liver forkhead box O1(FoxO1), phosphoenolpyruvate carboxykinase (PEPCK), glucose-6-phosphatase (G-6-P) and to explore the possible mechanisms.</p><p><b>METHODS</b>24 normal 6-week-old male Wistar rats were randomly divided into three groups: normal chow group (NC, n = 7), high fat diet group (HF, n = 9) and calorie restriction group (CR, n = 8). They were fed for 12 weeks. At the end of the experiment, the rats were sacrificed and their fasting blood glucose (FBG), insulin (INS), triglycerides (TG), total cholesterol (TC) were measured. Their visceral fat (VF) and body weight (BW) were also measured and VF/BW was calculated. Gene expression was investigated by using semi-quantitative RT-PCR methods. Liver histology was studied with HE stained slides.</p><p><b>RESULTS</b>Compared with the NC group, HF group rats developed visceral obesity which was accompanied by higher FBG, plasma INS, TG, and TC. The levels of FoxO1, PEPCK, and G-6-P increased by 18.9%, 33.8%, and 24.6%, respectively (P less than 0.01). Liver steatosis was observed with microscopy. The BW, VF FBG, INS, TG and TC of the CR group rats were lower in comparison to those of the HF group. The levels of FoxO1, PEPCK and G-6-P were lower by 26.6%, 35.0%, 34.3% (P less than 0.01). Meanwhile, liver steatosis was also milder.</p><p><b>CONCLUSION</b>Calorie restriction can inhibit the expressions of FoxO1, PEPCK and G-6-P, strengthen insulin signal conduction, suppress gluconeogenesis and thus regulate glycometabolism.</p>


Assuntos
Animais , Masculino , Ratos , Restrição Calórica , Gorduras na Dieta , Fatores de Transcrição Forkhead , Genética , Regulação da Expressão Gênica , Gluconeogênese , Genética , Glucose-6-Fosfatase , Genética , Fígado , Metabolismo , Proteínas do Tecido Nervoso , Genética , Fosfoenolpiruvato Carboxiquinase (ATP) , Genética , Ratos Wistar
17.
Journal of Forensic Medicine ; (6): 193-195, 2006.
Artigo em Chinês | WPRIM | ID: wpr-983178

RESUMO

OBJECTIVE@#To set up the method for analyzing HLA-B gene polymorphism with PCR-RFLP, and to gain population data among northern Chinese Hans of HLA-B's restricted fragments after NlaIII digestion, and to achieve application in forensic medicine practice.@*METHODS@#Sample DNA was extracted by the phenol/chloroform extraction method, 943 bp-long fragments containing HLA-B exon 2 and 3 were got by PCR. The endonuclease NlaIII was applied to cut the PCR products into polymorphic fragments shorter than 943bp, then PAGE and silver staining were used to detect the digestion results, finally the digestion sites were assured by DNA sequencing.@*RESULTS@#Along 943bp-long PCR products, 14 length-different fragments, 20 kinds of fragment combinations were got and 6 cutting site were observed after NlaIII digestion.@*CONCLUSION@#HLA-B gene was highly polymorphic among Chinese northern Hans. Even with only one endonuclease, 14 restricted fragments were got and the PIC was great. Such a HLA-B PCR-RFLP analysis will have values in forensic medicine applications.


Assuntos
Humanos , Povo Asiático/genética , Sequência de Bases , China/etnologia , DNA/isolamento & purificação , Éxons , Medicina Legal/métodos , Frequência do Gene , Antígenos HLA-B/genética , Reação em Cadeia da Polimerase/métodos , Polimorfismo de Fragmento de Restrição
18.
Chinese Journal of Integrated Traditional and Western Medicine ; (12): 143-146, 2005.
Artigo em Chinês | WPRIM | ID: wpr-284492

RESUMO

<p><b>OBJECTIVE</b>To observe the effect of Chinese herbs for supplementing Shen and strengthening bone (HB) on myelogenic osteoclasts formation, and gene expression of interleukin-6 (IL-6), IL-6 receptor (IL-6R) and gp130 in bone marrow.</p><p><b>METHODS</b>Seventy-two healthy female SD rats of 3 months, were randomly divided into three groups, 24 in the sham-operated group (A), 24 in the ovariectomized group (B) and 24 in the after ovariectomy HB treated group (C). Bone marrow cells of 6 rats from each group were respectively collected and cultured at four time points (2nd, 4th, 6th and 12th weeks after operation). After 6 days of culture, the bone marrow cells were differentiated by Wright-Giemsa stain and TRAP stain, and total RNA in them was extracted by TRIZOL.</p><p><b>RESULTS</b>Beginning from the 2nd week, the osteoclasts formation in Group B was higher than that in Group A (P < 0.05), and IL-6, IL-6R gene expression significantly increased in Group B (P < 0.05 or P < 0.01). These changes reached the peak in the 4th to 6th week, with the level maintained to the 12th week. As for comparison of Group B and C, the above-mentioned changes were significantly weakened in the latter (P < 0.05 or P < 0.01). No significant change of gp130 gene expression revealed in the whole course in either group.</p><p><b>CONCLUSION</b>HB could inhibit the myelogenic osteoclasts formation in ovariectomized rats, this effect may be correlated with, partially at least, its inhibitory effect on the over-expressed IL-6 and IL-6R gene expression in myelocytes after ovariectomy.</p>


Assuntos
Animais , Feminino , Ratos , Antígenos CD , Genética , Medula Óssea , Metabolismo , Divisão Celular , Células Cultivadas , Receptor gp130 de Citocina , Medicamentos de Ervas Chinesas , Química , Farmacologia , Células Precursoras de Granulócitos , Metabolismo , Interleucina-6 , Genética , Isoflavonas , Farmacologia , Glicoproteínas de Membrana , Genética , Osteoblastos , Patologia , Osteoporose , Metabolismo , Patologia , Ovariectomia , RNA , Genética , Distribuição Aleatória , Ratos Sprague-Dawley , Receptores de Interleucina-6 , Genética
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