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1.
Journal of Forensic Medicine ; (6): 726-732, 2019.
Article in English | WPRIM | ID: wpr-985071

ABSTRACT

Measurement of corpse temperature is mainly used for estimation of early postmortem interval, and rectal temperature is often used as a representative of body's core temperature in actual work because it is simple, quick and non-invasive. At present, the rectal temperature postmortem interval estimation method internationally accepted and widely used is HENSSGE's nomogram method, while many domestic scholars also deduced their own regression equations through a large number of case data. Estimation of postmortem interval based on rectal temperature still needs further study. The nomogram method needs to be optimized and extended, and quantification of its influencing factors needs to be dealt with more scientifically. There is still a lack of consensus on the probability and duration of the temperature plateau. There is no clear understanding of the probability and extent of the change in initial temperature caused by various causes. New methods and ideas enrich methodological research, but it still lacks systemicity and practicality. This article reviews the researches on estimation of postmortem interval based on rectal temperature in order to summarize the current situation of previous researches and seek new breakthrough points. Because the decline of body temperature can be easily influenced by many factors in vitro and vivo, and the influencing factors in different regions vary greatly, regionalization research and application may be a practical exploration to improve the accuracy of postmortem interval determination.


Subject(s)
Humans , Autopsy , Body Temperature , Cadaver , Postmortem Changes , Probability , Temperature , Time Factors
2.
Genomics, Proteomics & Bioinformatics ; (4): 154-168, 2019.
Article in English | WPRIM | ID: wpr-772943

ABSTRACT

N-methyladenosine (mA), catalyzed by the methyltransferase complex consisting of Mettl3 and Mettl14, is the most abundant RNA modification in mRNAs and participates in diverse biological processes. However, the roles and precise mechanisms of mA modification in regulating neuronal development and adult neurogenesis remain unclear. Here, we examined the function of Mettl3, the key component of the complex, in neuronal development and adult neurogenesis of mice. We found that the depletion of Mettl3 significantly reduced mA levels in adult neural stem cells (aNSCs) and inhibited the proliferation of aNSCs. Mettl3 depletion not only inhibited neuronal development and skewed the differentiation of aNSCs more toward glial lineage, but also affected the morphological maturation of newborn neurons in the adult brain. mA immunoprecipitation combined with deep sequencing (MeRIP-seq) revealed that mA was predominantly enriched in transcripts related to neurogenesis and neuronal development. Mechanistically, mA was present on the transcripts of histone methyltransferase Ezh2, and its reduction upon Mettl3 knockdown decreased both Ezh2 protein expression and consequent H3K27me3 levels. The defects of neurogenesis and neuronal development induced by Mettl3 depletion could be rescued by Ezh2 overexpression. Collectively, our results uncover a crosstalk between RNA and histone modifications and indicate that Mettl3-mediated mA modification plays an important role in regulating neurogenesis and neuronal development through modulating Ezh2.


Subject(s)
Animals , Adenosine , Metabolism , Adult Stem Cells , Cell Biology , Metabolism , Brain , Metabolism , Cell Differentiation , Genetics , Cell Proliferation , Enhancer of Zeste Homolog 2 Protein , Metabolism , Gene Expression Regulation , Methyltransferases , Metabolism , Mice, Inbred C57BL , Neural Stem Cells , Cell Biology , Metabolism , Neurogenesis , Genetics , Neurons , Cell Biology , Metabolism , RNA, Messenger , Genetics , Metabolism
3.
Chinese Journal of Hematology ; (12): 889-894, 2019.
Article in Chinese | WPRIM | ID: wpr-1012091

ABSTRACT

Objective: To investigate the current status and real performance of the detection of RUNX1-RUNX1T1 fusion transcript levels and WT1 transcript levels in China through interlaboratory comparison. Methods: Peking University People's Hospital (PKUPH) prepared the samples for comparison. That is, the fresh RUNX1-RUNX1T1 positive (+) bone morrow nucleated cells were serially diluted with RUNX1-RUNX1T1 negative (-) nucleated cells from different patients. Totally 23 sets with 14 different samples per set were prepared. TRIzol reagent was added in each tube and thoroughly mixed with cells for homogenization. Each laboratory simultaneously tested RUNX1-RUNX1T1 and WT1 transcript levels of one set of samples by real-time quantitative PCR method. All transcript levels were reported as the percentage of RUNX1-RUNX1T1 or WT1 transcript copies/ABL copies. Spearman correlation coefficient between the reported transcript levels of each participated laboratory and those of PKUPH was calculated. Results: ①RUNX1-RUNX1T1 comparison: 9 samples were (+) and 5 were (-) , the false negative and positive rates of the 20 participated laboratories were 0 (0/180) and 5% (5/100) , respectively. The reported transcript levels of all 9 positive samples were different among laboratories. The median reported transcript levels of 9 positive samples were from 0.060% to 176.7%, which covered 3.5-log. The ratios of each sample's highest to the lowest reported transcript levels were from 5.5 to 12.3 (one result which obviously deviated from other laboratories' results was not included) , 85% (17/20) of the laboratories had correlation coefficient ≥0.98. ②WT1 comparison: The median reported transcript levels of all 14 samples were from 0.17% to 67.6%, which covered 2.6-log. The ratios of each sample's highest to the lowest reported transcript levels were from 5.3-13.7, 62% (13/21) of the laboratories had correlation coefficient ≥0.98. ③ The relative relationship of the reported RUNX1-RUNX1T1 transcript levels between the participants and PKUPH was not always consistent with that of WT1 transcript levels. Both RUNX1-RUNX1T1 and WT1 transcript levels from 2 and 7 laboratories were individually lower than and higher than those of PKUPH, whereas for the rest 11 laboratories, one transcript level was higher than and the other was lower than that of PKUPH. Conclusion: The reported RUNX1-RUNX1T1 and WT1 transcript levels were different among laboratories for the same sample. Most of the participated laboratories reported highly consistent result with that of PKUPH. The relationship between laboratories of the different transcript levels may not be the same.


Subject(s)
Humans , China , Core Binding Factor Alpha 2 Subunit , Leukemia, Myeloid, Acute , RUNX1 Translocation Partner 1 Protein , Real-Time Polymerase Chain Reaction , Transcription, Genetic , WT1 Proteins
4.
Chinese Pharmacological Bulletin ; (12): 112-117, 2018.
Article in Chinese | WPRIM | ID: wpr-664573

ABSTRACT

Aim To observe the effect of thioesterase superfamily member 4 ( THEM4 ) expression on extra-cellular matrix ( ECM ) accumulation in the kidney of diabetic mice .Methods For in vivo vector delivery experiment , male CD1 mice were randomly divided in-to four groups: normal control mice ( Control group ) , diabetic mice ( DM group ) , diabetic mice receiving pYr-ads-4-THEM4 vector ( DM+THEM4 vector ) and diabetic mice receiving pYr-adshuttle-4 vector ( DM+V vector ) .pYr-ads-4-THEM4 vector or pYr-adshuttle-4 vector ( 1 mg · kg -1 ) were mixed with TransIT-EE Hydrodynamic Delivery Solution from Mirus Co .and injected into tail vein once a week for four weeks after STZ injection.Four weeks later, mice were sacrificed and Western blot , immunohistochemistry and real-time PCR were used to detect the expression of phospho-Akt(Ser 473), THEM4, TGF-β1, α-SMA, Col Ⅲ, FN proteins and THEM4 mRNA in kidneys respectively . Results THEM4 decreased in kidney of diabetes mel-litus accompanied with increased phospho-Akt ( Ser 473), TGF-β1, α-SMA and ECM.The delivery of pYr-ads-4-THEM4 vector increased THEM4 expression and decreased phospho-Akt (Ser 473), TGF-β1, α-SMA and ECM deposit in kidneys of diabetic mice . Conclusion The up-regulation of THEM4 may pre-vent ECM deposit by inhibiting the phosphorylation of Akt and down-regulating the expression of TGF-β1 andα-SMA in kidneys of diabetic mice .

5.
Genomics, Proteomics & Bioinformatics ; (4): 187-199, 2018.
Article in English | WPRIM | ID: wpr-772988

ABSTRACT

Non-small-cell lung cancer (NSCLC), the most common type of lung cancer accounting for 85% of the cases, is often diagnosed at advanced stages owing to the lack of efficient early diagnostic tools. 5-Hydroxymethylcytosine (5hmC) signatures in circulating cell-free DNA (cfDNA) that carries the cancer-specific epigenetic patterns may represent the valuable biomarkers for discriminating tumor and healthy individuals, and thus could be potentially useful for NSCLC diagnosis. Here, we employed a sensitive and reliable method to map genome-wide 5hmC in the cfDNA of Chinese NSCLC patients and detected a significant 5hmC gain in both the gene bodies and promoter regions in the blood samples from tumor patients compared with healthy controls. Specifically, we identified six potential biomarkers from 66 patients and 67 healthy controls (mean decrease accuracy >3.2, P < 3.68E-19) using machine-learning-based tumor classifiers with high accuracy. Thus, the unique signature of 5hmC in tumor patient's cfDNA identified in our study may provide valuable information in facilitating the development of new diagnostic and therapeutic modalities for NSCLC.


Subject(s)
Female , Humans , Male , Middle Aged , 5-Methylcytosine , Blood , Biomarkers, Tumor , Blood , Genetics , Carcinoma, Non-Small-Cell Lung , Blood , Diagnosis , Genetics , Case-Control Studies , Circulating Tumor DNA , Blood , DNA Methylation , Epigenomics , Lung Neoplasms , Blood , Diagnosis , Genetics
6.
Acta Pharmaceutica Sinica B ; (6): 353-360, 2017.
Article in English | WPRIM | ID: wpr-256747

ABSTRACT

Huperzine A (Hup-A) is a poorly water-soluble drug with low oral bioavailability. A self-microemulsifying drug delivery system (SMEDDS) was used to enhance the oral bioavailability and lymphatic uptake and transport of Hup-A. A single-pass intestinal perfusion (SPIP) technique and a chylomicron flow-blocking approach were used to study its intestinal absorption, mesenteric lymph node distribution and intestinal lymphatic uptake. The value of the area under the plasma concentration-time curve (AUC) of Hup-A SMEDDS was significantly higher than that of a Hup-A suspension (<0.01). The absorption rate constant () and the apparent permeability coefficient () for Hup-A in different parts of the intestine suggested a passive transport mechanism, and the values ofandof Hup-A SMEDDS in the ileum were much higher than those in other intestinal segments. The determination of Hup-A concentration in mesenteric lymph nodes can be used to explain the intestinal lymphatic absorption of Hup-A SMEDDS. For Hup-A SMEDDS, the values of AUC and maximum plasma concentration () of the blocking model were significantly lower than those of the control model (<0.05). The proportion of lymphatic transport of Hup-A SMEDDS and Hup-A suspension were about 40% and 5%, respectively, suggesting that SMEDDS can significantly improve the intestinal lymphatic uptake and transport of Hup-A.

7.
Chinese Pharmacological Bulletin ; (12): 1740-1743, 2017.
Article in Chinese | WPRIM | ID: wpr-667967

ABSTRACT

Aim To investigate the effect of thioester-ase superfamily member 4(THEM4)expression on col-lagen secretion in human renal proximal tubular epithe-lial cells (HKC)treated with high glucose. Methods In order to examine the direct effect of THEM4 ex-pression vector on PI3K/ Akt pathway and collagen se-cretion,pYr-ads-4-THEM4 expression vector was con-structed and transfected into the HKC with lipo-fectamine 2000 in vitro. HKC cells were randomly di-vided into four groups:normal glucose group (Con-trol),high glucose group (HG),high glucose plus pYr-ads-4-THEM4 vector group (HG + THEM4 vec-tor) and high glucose plus pYr-adshuttle-4 vector group (HG + V vector). After 48 h with HG stimula-tion,the cells were collected for extraction of protein and phospho-Akt (Ser 473),THEM4,TGF-β1 andα-SMA protein expression were examined by Western blot and immunofluorescence staining respectively. Col Ⅰ and Col Ⅲ were detected using the competitive sandwich ELISA kit according to the manufacturer's instructions. Results High glucose inhibited THEM4 expression,and induced increased phospho-Akt (Ser 473),TGF-β1,α-SMA and secreted ColⅠand secre-ted Col Ⅲ in HKC cells. Up-regulation of THEM4 re-versed high glucose-induced decreased THEM4,in-creased phospho-Akt (Ser 473),TGF-β1,α-SMA, secreted Col Ⅰ and secreted Col Ⅲ in HKC cells. Conclusion The up-regulation of THEM4 may de-crease Col Ⅰ and Col Ⅲ secretion by inhibiting the phosphorylation of Akt and down-regulating the expres-sion of TGF-β1 and α-SMA in high glucose-induced HKC cells.

8.
Biol. Res ; 50: 24, 2017. graf
Article in English | LILACS | ID: biblio-950875

ABSTRACT

BACKGROUND: The aim of the present study was to investigate the potential effects of the 5,10,15,20-tetrakis (1-methylpyridinium-4-yl) porphyrin (TMPyP4) on the proliferation and apoptosis of human cervical cancer cells and the underlying mechanisms by which TMPyP4 exerted its actions. RESULTS: After human cervical cancer cells were treated with different doses of TMPyP4, cell viability was determined by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) method, the apoptosis was observed by flow cytometry (FCM), and the expression of p38 mitogen-activated protein kinase (MAPK), phosphated p38 MAPK (p-p38 MAPK), capase-3, MAPKAPK2 (MK-2) and poly ADP-ribose polymerase (PARP) was measured by Western blot analysis. The analysis revealed that TMPyP4 potently suppressed cell viability and induced the apoptosis of human cervical cancer cells in a dose-dependent manner. In addition, the up-regulation of p-p38 MAPK expression levels was detected in TMPyP4-treated human cervical cancer cells. However, followed by the block of p38 MAPK signaling pathway using the inhibitor SB203580, the effects of TMPyP4 on proliferation and apoptosis of human cervical cancer cells were significantly changed. CONCLUSIONS: It was indicated that TMPyP4-inhibited proliferation and -induced apoptosis in human cervical cancer cells was accompanied by activating the p38 MAPK signaling pathway. Taken together, our study demonstrates that TMPyP4 may represent a potential therapeutic method for the treatment of cervical carcinoma.


Subject(s)
Humans , Female , Porphyrins/pharmacology , Uterine Cervical Neoplasms/drug therapy , p38 Mitogen-Activated Protein Kinases/metabolism , Antineoplastic Agents/pharmacology , Tetrazolium Salts , HeLa Cells/drug effects , Cell Survival/drug effects , Cells, Cultured , Blotting, Western , Reproducibility of Results , Apoptosis/drug effects , p38 Mitogen-Activated Protein Kinases/antagonists & inhibitors , Cell Proliferation/drug effects , Enzyme Activation/drug effects , Caspase 3/analysis , Formazans
9.
Journal of Huazhong University of Science and Technology (Medical Sciences) ; (6): 343-7, 2014.
Article in English | WPRIM | ID: wpr-636620

ABSTRACT

This study was aimed to screen human papillomavirus (HPV) types associated with esophageal squamous cell carcinoma of Kazakh in Xinjiang using the gene chip technique and study the clinical significance of this application. The DNAs were collected from esophageal squamous cell carcinoma tissues and healthy esophageal mucosa of Kazakh adults in Xinjiang, and amplified firstly using HPV MY09/11 and then using HPV G5+/6+ to screen positive HPV specimens. These positive specimens were further detected by the gene chip technique to screen highly pathogenic HPV types. After determination with nested PCR amplification with HPV MY09/11 and G5+/6+, the infection rate of HPV was 66.67% in the esophageal squamous cell carcinoma group and 12.12% in the healthy control group. By testing the positive HPV specimens from the esophageal squamous cell carcinoma group, the infection rate of HPV16 was 97.72% and the co-infection rate of HPV16 and HPV18 was 2.27%. HPV16 infection may be involved in the development of esophageal squamous cell carcinoma in Xinjiang Hazakh adults.

10.
Journal of Huazhong University of Science and Technology (Medical Sciences) ; (6): 343-347, 2014.
Article in English | WPRIM | ID: wpr-351074

ABSTRACT

This study was aimed to screen human papillomavirus (HPV) types associated with esophageal squamous cell carcinoma of Kazakh in Xinjiang using the gene chip technique and study the clinical significance of this application. The DNAs were collected from esophageal squamous cell carcinoma tissues and healthy esophageal mucosa of Kazakh adults in Xinjiang, and amplified firstly using HPV MY09/11 and then using HPV G5+/6+ to screen positive HPV specimens. These positive specimens were further detected by the gene chip technique to screen highly pathogenic HPV types. After determination with nested PCR amplification with HPV MY09/11 and G5+/6+, the infection rate of HPV was 66.67% in the esophageal squamous cell carcinoma group and 12.12% in the healthy control group. By testing the positive HPV specimens from the esophageal squamous cell carcinoma group, the infection rate of HPV16 was 97.72% and the co-infection rate of HPV16 and HPV18 was 2.27%. HPV16 infection may be involved in the development of esophageal squamous cell carcinoma in Xinjiang Hazakh adults.


Subject(s)
Aged , Female , Humans , Male , Middle Aged , Asian People , Carcinoma, Squamous Cell , Ethnology , Genetics , Virology , Case-Control Studies , China , DNA, Neoplasm , Genetics , DNA, Viral , Genetics , Esophageal Neoplasms , Ethnology , Genetics , Virology , Host-Pathogen Interactions , Genetics , Human papillomavirus 16 , Genetics , Human papillomavirus 18 , Genetics , Molecular Typing , Methods , Oligonucleotide Array Sequence Analysis , Methods , Papillomaviridae , Classification , Genetics , Physiology , Papillomavirus Infections , Ethnology , Genetics , Virology , Polymerase Chain Reaction
11.
Chinese Journal of Hematology ; (12): 104-108, 2013.
Article in Chinese | WPRIM | ID: wpr-323434

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the comparability of bcr-abl (P210) transcript levels detected in different hospitals.</p><p><b>METHODS</b>Ten hospitals in China took part in the four times of sample exchange and comparisons from April, 2010 to August, 2011. The exchange samples were prepared by Peking University People's Hospital. Firstly, the BCR-ABL (P210)(+) cells from a newly diagnosed chronic myeloid leukemia patient were 10-fold serially diluted by BCR-ABL (P210)(-) cells and they covered 4 magnitudes. Then, TRIzol reagents were thoroughly mixed with cells in each tube. Every 12 samples (three samples per magnitude) were sent to the other 9 hospitals. The cell number of each sample was 8×10(6). The detection of bcr-abl transcript levels by real-time quantitative PCR were performed in every hospital according to their own protocols. Conversion factors (CF) were calculated using regression equation.</p><p><b>RESULTS</b>Differences in bcr-abl transcript levels did exist among results of 10 hospitals in each comparison. In general, the results of the most of hospitals were in line with the dilutions of cells. CF of every hospital fluctuated. Three hospitals had relatively stable CF, and their ranges were 2.8 - 5.2, 1.2 - 2.8 and 2.2 - 6.8, respectively; two hospitals had unstable CF with ranges 0.76 - 7.0 and 2.1 - 18.7; three hospitals couldn't be calculated CF one or two times because of the significant deviation of the results from the actually bcr-abl transcript levels, and their ranges of CF which could be calculated were 1.9 - 19.2, 3.6 - 7.6 and 0.18 - 14.7; One hospital only had two CF (3.3 and 5.0) because of the replacement of an important reagent during the period of comparisons.</p><p><b>CONCLUSIONS</b>Comparability of bcr-abl (P210) transcript levels between different hospitals could be achieved through CF which acquired by sample exchange and comparison. The stable and reliable detection system is the premise to acquire correct CF.</p>


Subject(s)
Humans , Bone Marrow Cells , China , Fusion Proteins, bcr-abl , Genetics , Hospitals , Leukemia, Myelogenous, Chronic, BCR-ABL Positive , Diagnosis , Genetics , Reverse Transcriptase Polymerase Chain Reaction
12.
Chinese Journal of Practical Nursing ; (36): 12-15, 2013.
Article in Chinese | WPRIM | ID: wpr-429875

ABSTRACT

Objective To explore the influence of score sheet of colostomy on reduction of complication in non-hospitalized patients with colostomy stoma.Methods 186 patients with colostomy stoma were randomly divided into group A and group B.Group A used the score sheet of colostomy with nurses during hospitalization and after discharge.Group B were in routine treatment without using the score sheet of colostomy.The two groups were followed-up by phone or by visiting in the following 1,3,6 months after discharge.Results The complications between the two groups were evaluated.The risk of the complications was only 14.0% in group A,and the risk in group B was 36.6%.The results of self-satisfaction degree was significantly different between two groups.Conclusions The use of the score sheet of colostomy can significantly reduce the incidence of stoma complications and obviously improve the quality of life of the patients with colostomy.

13.
Chinese Journal of Industrial Hygiene and Occupational Diseases ; (12): 602-605, 2013.
Article in Chinese | WPRIM | ID: wpr-275874

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the effects of electromagnetic radiation on the physiological indices and immune function of operators.</p><p><b>METHODS</b>The general conditions and electromagnetic radiation awareness rate of 205 operators under electromagnetic radiation were evaluated using a self-designed questionnaire. Physical examination, electrocardiography, and routine urine test were performed in these operators. Peripheral blood was collected from the operators under electromagnetic radiation for blood cell counting and biochemical testing, and their peripheral blood lymphocytes were cultured for determination of chromosomal aberrant frequency and micronucleus frequency. The data from these operators (exposure group) were compared with those of 95 ordinary individuals (control group).</p><p><b>RESULTS</b>The chief complaint of giddiness, tiredness, dizziness, and amnesia showed significant differences between the exposure group and control group (P < 0.01), and the difference in headache became larger with an increase in working years. The awareness rate of electromagnetic radiation damage was significantly higher in the exposure group than in the control group. The difference in bradycardia was significant between the two groups (P <0.01), and the incidence was higher with longer working years. Significant differences between the two groups were also found in the numbers of individuals with elevated alanine aminotransferase, total bilirubin, and direct bilirubin (P < 0.01), populations with increased lymphocyte ratio and decreased neutrophil ratio (P < 0.01), populations with positive occult blood, urobilinogen, and bilirubin tests, and the number of individuals with increased micronucleus frequency of cultured peripheral blood lymphocytes (P < 0.01). In addition, the exposure group had significantly increased complement C3 and C4 (P < 0.01), significantly increased IgG (P < 0.05), and significantly decreased IgM (P < 0.01), as compared with the control group.</p><p><b>CONCLUSION</b>Electromagnetic radiation may lead to the changes in physiological indices, genetic effects, and immune function and affect the health and immune function in operators. The adverse effects are increased as the working years increase. So it is important to strengthen occupational protection of operators under electromagnetic radiation.</p>


Subject(s)
Adult , Female , Humans , Male , Middle Aged , Young Adult , Chromosome Aberrations , Radiation Effects , Electromagnetic Radiation , Lymphocytes , Radiation Effects , Occupational Exposure
14.
Acta Academiae Medicinae Sinicae ; (6): 519-523, 2013.
Article in Chinese | WPRIM | ID: wpr-285967

ABSTRACT

<p><b>OBJECTIVE</b>To explore the association of fractalkine (FKN) and CD11c expressions oncommon carotid artery atherosclerotic plaques from apoE(-/-) mice with the severity of atherosclerotic lesions.</p><p><b>METHODS</b>Totally 24 apoE(-/-) mice were divided into two groups and fed on a high-fat diet or a normal diet for 12 weeks. Then the blood lipids as well as the plaque area and vascular stenosis rate of the common carotid artery were measured to evaluate the severity of atherosclerotic lesions of the animals. Moreover, immunohistochemical staining was performed to examine the levels of FKN and CD11c expression.</p><p><b>RESULTS</b>The plaque areas and vascular stenosis rates of the common carotid artery in the experimental group were remarkably larger than those in control group (about 4-fold and 2-fold, respectively). The level of FKN expression in the experimental group was 2 times of that in the control group (P<0.05), and the number of CD11c (+) cells in the plaques in the experimental group was about 4 times of than in the control group (P<0.05).</p><p><b>CONCLUSION</b>The expressions of chemokine and FKN remarkably increase in apoE (-/-) atherosclerotic plaques, suggesting that chemokine and FKN may paly important roles in the development of atherosclerosis.</p>


Subject(s)
Animals , Mice , Atherosclerosis , Metabolism , Pathology , CD11 Antigens , Metabolism , Chemokine CX3CL1 , Metabolism , Diet, High-Fat , Disease Models, Animal , Mice, Knockout , Plaque, Atherosclerotic , Pathology
15.
Chinese Journal of Hematology ; (12): 825-829, 2013.
Article in Chinese | WPRIM | ID: wpr-272106

ABSTRACT

<p><b>OBJECTIVE</b>To evaluate the efficacy and safety of the HAA regimen (homoharringtonine, cytarabine and aclarubicin) as induction chemotherapy in de novo acute myeloid leukemia (AML).</p><p><b>METHODS</b>The efficacy and safety of 236 de novo AML patients who received the HAA regimen as induction chemotherapy were retrospectively analyzed. The complete remission (CR) rate was assayed. Kaplan-Meier method was used to estimate overall survival (OS) and relapse free survival (RFS), and the differences were compared by Log-rank test.</p><p><b>RESULTS</b>The overall CR rate was 78.0%, and 65.7% of the patients attained CR in the first induction cycle. The early death rate was 4.7%. The median followup time was 41(1-161) months. The estimated 5-year OS and 5-year RFS rates were 44.9% and 45.5%, respectively. The CR rates of patients with favorable, intermediate and unfavorable cytogenetics were 92.9%,78.6%and 41.7%, respectively. The 5-year OS of favorable and intermediate group were 61.1% and 45.1%, respectively. The 5- year RFS of favorable and intermediate group were 49.0% and 45.4%, respectively. The median survival time of unfavorable group was only 5 months. The side effects associated with the HAA regimen were tolerable, in which the most common toxicities were myelosuppression and infection.</p><p><b>CONCLUSION</b>The HAA regimen is associated with a higher rate of CR and longer survival time and its toxicity could be tolerated.</p>


Subject(s)
Adolescent , Adult , Female , Humans , Male , Middle Aged , Young Adult , Antineoplastic Combined Chemotherapy Protocols , Therapeutic Uses , Leukemia, Myeloid, Acute , Drug Therapy , Retrospective Studies
16.
Chinese Journal of Medical Genetics ; (6): 64-67, 2012.
Article in Chinese | WPRIM | ID: wpr-295531

ABSTRACT

<p><b>OBJECTIVE</b>To investigate cytogenetic features and outcome of chromosomal abnormalities in Philadelphia negative cells (Ph(-)CAs) of chronic myelogenous leukemia (CML) patients treated with tyrosine kinase inhibitors.</p><p><b>METHODS</b>Clinical and laboratory data of 15 CML patients in which Ph(-)CAs occurred after tyrosine kinase inhibitors therapy were collected and analyzed.</p><p><b>RESULTS</b>Of 15 cases with Ph(-)CAs, 12 patients were treated with imatinib, 2 were treated with dasatinib and 1 was treated with bosutinib. + 8 was the most common abnormality in Ph(-)CAs, which accounted for 46.7% of all. Ph(-)CAs usually occurred when Ph(+)cells decreased or disappeared due to tyrosine kinase inhibitors therapy. The average time for the appearance of Ph(-)CAs was 11.1 months (1-28 months). In 7 patients, the Ph(-)CAs have disappeared in 10.9 months (3-24 months). In such patients, no myelodysplastic syndrome or acute leukemia was observed. One patient has progressed to acute monocytic leukemia with Ph(+)cells. All remaining patients have achieved bone morrow remission, among which 11 patients achieved complete cytogenic response and 4 patients even achieved complete molecular response.</p><p><b>CONCLUSION</b>The majority of Ph(-)CAs developed in CML patients are transient in nature. They may develop following imatinib, dasatinib or bosutinib therapy but do not interfere with the therapeutic effects of tyrosine kinase inhibitors.</p>


Subject(s)
Adult , Female , Humans , Male , Middle Aged , Young Adult , Chromosome Aberrations , Leukemia, Myelogenous, Chronic, BCR-ABL Positive , Drug Therapy , Genetics , Protein Kinase Inhibitors , Pharmacology , Protein-Tyrosine Kinases
17.
Chinese Journal of Hematology ; (12): 814-818, 2011.
Article in Chinese | WPRIM | ID: wpr-345980

ABSTRACT

<p><b>OBJECTIVE</b>To study the clinical characteristics, risk factors and therapeutic outcome of Philadelphia chromosome-positive adult acute lymphoblastic leukemia (Ph(+)aALL).</p><p><b>METHODS</b>The clinical data of 117 newly diagnosed adults with Ph(+)ALL in our hospital between January 1995 and December 2009 were retrospectively analyzed. And their prognoses were followed up.</p><p><b>RESULTS</b>There were 117(16.1%) of 727 aALL patients diagnosed as Ph(+)aALL. Among the 117 cases, 64.1% patients were classified as pre-B immunophenotype and 31.3% as common B immunophenotype, 37.5% patients with co-expression of myeloid antigens (CD13 or CD33), and 98.4% patients with positive CD34. The complete remission (CR) rate after 1 or 2 cycles of induction chemotherapy was 62.2% in Ph(+)aALL group versus 82% in Ph(-)aALL group (P = 0.000). The median disease-free survival time of Ph(+) group was 6 months and the median survival time was 9 months. Sole karyotype abnormality subgroup t(9;22) accounted for 53% of all Ph(+)aALL patients and additional karyotype abnormality subgroup, t(9;22) plus other chromosome variation, accounted for 47%. Patients in sole karyotype abnormality subgroup had slightly lower CR rate (59.6% vs 62.5%, P = 0.768), longer median survival time (7 months vs 4 months, P = 0.158), and higher 3-year overall survival rate (27.3% vs 14.4%, P = 0.271). For the myeloid antigen co-expressed patients and the only lymphocytic antigen expressed ones, CR rate was 56.0% and 61.5% (P = 0.750), the median survival time was 5 months and 4 months (P = 0.182), and the 3-year overall survival rate was 16.0% and 15.0% (P = 0.354), respectively. In the imatinib plus combination chemotherapy treatment group, 81.3% patients achieved CR, compared with that of 58.3% in patients treated with only traditional combination chemotherapy (P = 0.083). The median survival time was 9.5 months and 6 months (P = 0.003) in these two subgroup, and 3-year overall survival rate was 52.2% and 10.3% (P = 0.029), respectively. For the patients receiving allo-HSCT after CR and that receiving traditional consolidation chemotherapy, the median survival time was 15 months and 6 months (P = 0.000), and the 3-year overall survival rate was 62.0% and 10.3% (P = 0.000), respectively. For the patients receiving imatinib as consolidation-maintenance treatment and that receiving allo-HSCT, the median survival time was 12 months and 15 months (P = 0.300), and the 3-year overall survival rate was 64.7% and 62% (P = 0.505), respectively.</p><p><b>CONCLUSION</b>Of all adult ALL patients, the Ph(+) subgroup accounted for about 16.1%, which have unfavorable prognosis such as lower CR rate and shorter survival duration under traditional chemotherapy. Neither additional chromosome abnormalities to t(9;22) nor co-expression of myeloid antigen had negative effect on CR rate and survival duration. Addition of imatinib to the therapy was beneficial to improve the CR rate and survival duration. Either receiving imatinib as consolidation-maintenance treatment or allo-HSCT after complete remission can improve long-term survival rate of Ph(+) adult ALL group significantly.</p>


Subject(s)
Adult , Female , Humans , Male , Benzamides , Imatinib Mesylate , Philadelphia Chromosome , Piperazines , Therapeutic Uses , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Diagnosis , Drug Therapy , Genetics , Prognosis , Pyrimidines , Therapeutic Uses , Retrospective Studies
18.
Journal of Zhejiang University. Medical sciences ; (6): 236-240, 2010.
Article in Chinese | WPRIM | ID: wpr-259210

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the cytogenetic features of acute myeloid leukemia (AML) with t(8;21).</p><p><b>METHODS</b>The clinical characteristics of 154 cases of acute myeloid leukemia with t(8;21) in our hospital were analyzed retrospectively. According to the chromosome karyotype, all cases were divided into three groups: the group without additional chromosome abnormality, the group with single sex chromosome loss and the group with additional chromosome abnormalities other than sex chromosome loss.</p><p><b>RESULT</b>In this study, according to FAB classification, there were 127 cases of M2 (82.5%), 15 of M5 (9.7%), 6 of M4 (3.9%), 4 of M1(2.6%) and 2 of M0(1.3%). Cytogenetically, 85 (55.2%) AML patients with t(8;21) had additional chromosome abnormalities. The most common abnormalities were sex chromosome loss, of which -Y was detected in 44.1% of the male karyotype and X in 27.9%. Beside that, there were 9 cases of 9q- (5.8%), 5 of +8(3.3%),3 of +4(2.0%) and 17 of other chromosome anomalies (11.4%). In the group of t(8;21) with additional chromosome abnormalities, 11 cases (35.5%) were non-M2 AML, higher than that in single t(8;21) group (17.4%)(P<0.05); however, there was no significant difference between the group of single t(8;21) and the group of t(8;21) with single sex chromosome loss(P>0.05).</p><p><b>CONCLUSION</b>t(8;21) translocation is usually accompanied by additional chromosome abnormalities, particularly in M2; while t(8;21) with additional chromosome abnormalities other than sex chromosome loss is more frequently observed in non-M2 AML.</p>


Subject(s)
Adolescent , Adult , Female , Humans , Male , Middle Aged , Young Adult , Chromosome Aberrations , Chromosomes, Human, Pair 21 , Genetics , Chromosomes, Human, Pair 8 , Genetics , Cytogenetic Analysis , Leukemia, Myeloid, Acute , Classification , Genetics , Prognosis , Retrospective Studies , Translocation, Genetic
19.
Chinese Journal of Hematology ; (12): 741-745, 2008.
Article in Chinese | WPRIM | ID: wpr-239964

ABSTRACT

<p><b>OBJECTIVE</b>To evaluate the prevalence of FLT3 gene expression and internal tandem duplication (ITD) mutation in acute myeloid leukemia (AML) patients and its clinical significance.</p><p><b>METHODS</b>The expression level of FLT3 mRNA was detected with real-time quantitative RT-PCR (RQ-PCR) technique in 152 bone marrow samples from 129 AML patients. The ITD of the FLT3 gene (FLT3/ITD) was detected in 75 de novo AML patients by reverse transcription polymerase chain reaction (RT-PCR).</p><p><b>RESULTS</b>The expression levels of FLT3 mRNA was 0.0020(0.0006 - 0.0040) in normal controls, and 0.1041 (0 - 33.8736) in 80 de novo AML patients (P = 0.001). FLT3/ITDs were found in 11 (14.7%) of 75 de novo AML patients. The FLT3 expression levels in patients with FLT3/ITD were 0.0297 to 33.8736 with a median level of 0.2200, and in those without FLT3/ITD were 0 to 26.2200 with a median level of 0.0975. The FLT3 expression levels in the former patients were higher than that in the latter ones, but there was no statistical significance (P = 0.093). The complete remission (CR) rate was lower in acute promyelocytic leukemia (APL) patients with FLT3/ITD than in APL patients without FLT3/ITD (P = 0.015). In de novo AML other than APL patients without FLT3/ITD, the CR rate was lower in patients with higher levels of FLT3 expression (expression level > 0.04, CR rate 37.5%) than those with lower levels of FLT3 expression (expression level < 0.04, CR rate 100%). On follow-up of 20 patients, the FLT3 expression level was decreased at least one logarithm degree when they got CR, but it was no significant change in non-remission patients.</p><p><b>CONCLUSIONS</b>Quantification of FLT3 mRNA expression level and detection of FLT3/ITD in AML patients may serve as an index for evaluating therapeutic efficacy, predicting prognosis, and monitoring minimal residual disease.</p>


Subject(s)
Adolescent , Adult , Aged , Aged, 80 and over , Child , Female , Humans , Male , Middle Aged , Young Adult , Leukemia, Myeloid, Acute , Genetics , Mutation , Prognosis , RNA, Messenger , Genetics , Reverse Transcriptase Polymerase Chain Reaction , Tandem Repeat Sequences , Treatment Outcome , fms-Like Tyrosine Kinase 3 , Genetics
20.
Chinese Journal of Hematology ; (12): 1-5, 2007.
Article in Chinese | WPRIM | ID: wpr-328383

ABSTRACT

<p><b>OBJECTIVE</b>To evaluate the cytogenetic and molecular genetic features of chronic myeloid leukemia (CML) in Chinese.</p><p><b>METHODS</b>A total of 1193 CML patients were retrospectively studied. Chromosome preparation of bone marrow cells was made using direct and short-term culture. Karyotype and bcr-abl fusion genes were analyzed by R-banding, RT-PCR, respectively.</p><p><b>RESULTS</b>In the 1193 cases, 98.07% was Ph chromosome positive (Ph+) and 1.93% negative (Ph-). In the Ph+ patients, 95.64% was classical Ph and 4.36% variant rearrangements. Additional genetic changes were demonstrated in 11.88% of classical Ph cases. Cytogenetic clonal evolution was found in 7.94% of patients in chronic phase (CP), 27.78% in accelerated phase (AP), and 49. 04% in blast crisis (BC). Among the classical Ph cases, +Ph, +8, -21 were found in 14.62%, 10.77% and 7.69% of them respectively. In patients in BC and AP, the most common additional chromosome changes were + Ph (28.57%), +8 (16.67%) and +19 (7.14%), while in CP, -21 (10.26%), +Ph (8.97%), and +8 (8.97%). The combination of +Ph and +8 (3.60%) was the most frequent of combination pattern. 524 cases were investigated for bcr-abl fusion gene, and 54.01% was b3a2 (+) and 27.67% b2a2 (+).</p><p><b>CONCLUSION</b>In Chinese CML patients seem to have their unique features in terms of cytogenetic clonal evaluation.</p>


Subject(s)
Adolescent , Adult , Aged , Child , Child, Preschool , Female , Humans , Male , Middle Aged , Fusion Proteins, bcr-abl , Genetics , Karyotyping , Leukemia, Myelogenous, Chronic, BCR-ABL Positive , Genetics , Retrospective Studies
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