Effect of Danhong Injection on platelet metabolites based on metabonomics technology / 中国中药杂志

The effect of Danhong Injection on the endogenous metabolites of rabbit platelets was analyzed by the liquid chromatography-mass spectrometry( LC-MS) based metabonomic approach. Anti-platelet aggregation was detected after Danhong Injection treatment and the changes of platelet metabolites were analyzed by metabonomics. Principal component analysis( PCA) and partial least squares discriminant analysis( PLS-DA) were performed to investigate the effect of Danhong Injection on endogenous metabolites of platelets,characterize the biomarkers,and explore the relevant pathways and the underlying mechanism. As demonstrated by the pharmacodynamic results,Danhong Injection of different doses and concentrations antagonized platelet aggregation in a dose-and concentration-dependent manner. In contrast to the control group,25 differential metabolites such as nicotinic acid,nicotinic acid riboside,and hypoxanthine were screened out after platelets were treated by Danhong Injection. These metabolites,serving as important biomarkers,were mainly enriched in the nicotinic acid-niacinamide metabolic pathway and purine metabolic pathway. This study explored the therapeutic mechanism of Danhong Injection from a microscopic perspective by metabonomics,which is expected to provide a new idea for the investigation of platelet-related mechanisms.

China experts' consensus on preventive and interceptive orthodontic treatments of malocclusions of children / 华西口腔医学杂志

Malocclusion is one of the three most common oral diseases reported by World Health Organization(WHO). In China, its incidence rate is rising. Malocclusion seriously affects the dental and maxillofacial function, facial appearance and growth development of nearly 260 million children in China, and what is more, it affects their physical and mental health development. Malocclusion occurrence is related to genetic and environmental factors. Early treatment of malocclusion can create a good dental and maxillofacial development environment, correct abnormal growth and control the adverse effects of abnormal genetic factors. It can effectively reduce the prevalence of children's malocclusion and enhance their physical and mental health. This is an urgent need from the economic perspective of our society, so it has great practical and social significance. Experts from the project group "standard diagnose and treatment protocols for early orthodontic intervention of malocclusions of children" which initiated by China National Health Institute of Hospital Administration wrote the "China Experts' Consensus on Preventive and Interceptive Orthodontic Treatments of Malocclusions of Children", which aims to guide and popularize the clinical practice, improve the clinical theory and practice level, and accelerate the disciplinary development of early treatment of children's malocclusion in China. The consensus elaborates the harmfulness of malocclusion and the necessity of early treatment, and brings up the principles and fundamental contents. Based on the law of dental and maxillofacial development, this paper puts forward the guiding suggestions of preventive and interceptive treatments in different stages of dental development ranging from fetus to early permanent dentition. It is a systematic project to promote and standardize the early treatment of malocclusion. Through scientific and comprehensive stratified clinical practice and professional training, the clinical system of early treatment of malocclusion in China will eventually be perfected, so as to comprehensively care for children's dental and maxillofacial health, and improve their oral and physical health in China.

Analysis and comparison of metabolic processes of salvianolic acid A and salvianolic acid B in rats based on UHPLC-LTQ-Orbitrap MS technology / 中国中药杂志

The metabolites of salvianolic acid A and salvianolic acid B in rats were analyzed and compared by ultra-high-perfor-mance liquid chromatography with linear ion trap-orbitrap mass spectrometry(UHPLC-LTQ-Orbitrap MS). After the rats were administrated by gavage, plasma at different time points and urine within 24 hours were collected to be treated by solid phase extraction(SPE), then they were gradient eluted by Acquity UPLC BEH C_(18) column(2.1 mm×100 mm, 1.7 μm) and 0.1% formic acid solution(A)-acetonitrile(B) mobile phase system, and finally all biological samples of rats were analyzed under negative ion scanning mode. By obtaining the accurate relative molecular mass and multi-level mass spectrometry information of metabolites, combined with the characteristic cleavage law of the reference standard and literature reports, a total of 30 metabolites, including salvianolic acid A and B, were identified. Among them, there were 24 metabolites derived from salvianolic acid A, with the main metabolic pathways including ester bond cleavage, dehydroxylation, decarboxylation, hydrogenation, methylation, hydroxylation, sulfonation, glucuronidation, and their multiple reactions. There were 15 metabolites of salvianolic acid B, and the main biotransformation pathways were five-membered ring cracking, ester bond cleavage, decarboxylation, dehydroxylation, hydrogenation, methylation, sulfonation, glucuronidation, and their compound reactions. In this study, the cross-metabolic profile of salvianolic acid A and B was elucidated completely, which would provide reference for further studies on the basis of pharmacodynamic substances and the exploration of pharmacological mechanism.

Analysis of carnosic acid metabolites in rats by UHPLC-Q-Exactive MS / 中国中药杂志

A method of ultra-high performance liquid chromatography coupled with quadrupole/electrostatic field Obitrap high-resolution mass spectrometry(UHPLC-Q-Exactive MS) was established to comprehensively identify the metabolites of carnosic acid in rats. After oral gavage of carnosic acid CMC-Na suspension in rats, urine, plasma and feces samples were collected and pretreated by solid phase extraction(SPE). Acquity UPLC BEH C_(18 )column(2.1 mm×100 mm, 1.7 μm) was used with 0.1% formic acid solution(A)-acetonitrile(B) as the mobile phase for the gradient elution. Biological samples were analyzed by quadrupole/electrostatic field Obitrap high-resolution mass spectrometry in positive and negative ion mode. Based on the accurate molecular mass, fragment ion information, and related literature reports, a total of 28 compounds(including carnosic acid) were finally identified in rat samples. As a result, the main metabolic pathways of carnosic acid in rats are oxidation, hydroxylation, methylation, glucuronide conjugation, sulfate conjugation, S-cysteine conjugation, glutathione conjugation, demethylation, decarbonylation and their composite reactions. The study showed that the metabolism of carnosic acid in rats could be efficiently and comprehensively clarified by using UHPLC-Q-Exactive MS, providing a reference for clarifying the material basis and metabolic mechanism of carnosic acid.

Bioassay method for Compound Danshen Tablets based on a platelet aggregation inhibition test / 药学学报

A bioassay method for inhibiting platelet aggregation in vitro was established to quantify the pharmacological effects of Compound Danshen Tablets and support its quality control. The inhibition of platelet aggregation in rabbit plasma in vitro by Compound Danshen Tablets was used as the experimental system. The titer was calculated by using the method of dose-response parallel lines. As a result, a bioassay for the inhibition of platelet aggregation in vitro by Compound Danshen Tablets was established. Linearity was good in the concentration range of 0.128 g·mL-1 to 0.205 g·mL-1, and the titer of standard Compound Danshen tablets was 7 659 U·g-1 according to the titer definition. This in vitro assay was simple, reliable, reproducible and convenient. The activity of Compound Danshen Tablets in inhibiting platelet aggregation was quantified by potency assay and the quality of different batches was evaluated. The method can be applied for the quality control of Compound Danshen Tablets.

Clinical features and prognosis of acute monocytic leukemia with abnormality of chromosome 8 / 中国实用内科杂志

OBJECTIVE: To investigate the clinical characteristics and prognosis of patients with acute monocytic leukemia(AML-M5)with abnormality of chromosome 8.METHODS: The clinical features of 143 patients with AML-M5 were analyzed retrospectively,and the prognosis factors were analyzed.RESULTS: Out of 143 AML-M5 newly diagnosed patients,37 cases with chromosome 8 aberrations including t(8;21)accounting for 6.99%(10/143),trisomy 8 16.08%(23/143),and other 8 aberrations 2.80%(4/143);73 cases had normal karyotype,and 33 cases possessed non chromosome 8 abnormality.Statistically significant differences did not exist among age,sex,hemogram and bone marrow blasts(P>0.05).However,with chromosome 8 abnormality were predisposed to lower initial white blood cell count(P<0.05).Among 131 patients of receiving chemotherapy,the remission rate after the first course of inducible chemotherapy was 63.36%(83/131)and the one-year survival rate was 61.1%.Analysis of prognostic factors showed that age,the remission after the first induction of chemotherapy(complete remission or no remission),trisomy 8 chromosomal karyotype and treatment regimen(chemotherapy alone or plus hematopoietic stem cell transplantation) had effects on overall survival(P<0.05).Multivariate analysis revealed two independent risk factors:age≥60 years(P<0.05,HR=2.134,95% CI 1.204～3.784)and the complete remission after the first induction of chemotherapy(P<0.05,HR=0.408,95% CI 0.227～0.733).CONCLUSION: Chromosome 8 is easily involved in AML-M5.The patients with involvement of this aberration have lower initial white blood cell count and a poor prognosis.Patients after complete remission have hematopoietic stem cell transplantation is beneficial to prolong survival.

Therapeutic effect and mechanism of breviscapine on cisplatin-induced nephrotoxicity in mice

Objective: To observe the protective effect of breviscapine on mice with cisplatin-induced nephrotoxicity. Methods: Mice were given a single injection of cisplatin (8 mg/kg, i.p.); then, breviscapine was given to mice at 25 mg/kg and 50 mg/kg doses, respectively, once a day for seven days. Renal tissue structure was observed after animals were sacrificed. Blood urea nitrogen (BUN), serum creatinine (Scr), lipid peroxide (MDA) and superoxide dismutase (SOD) serum levels were detected; and MDA, glutathione peroxidase, and SOD levels in the renal cortex were detected. Results: Compared with the blank control group (BCG), the kidney pathological damage of mice in the model control group (MCG) was more severe. After applying different doses of breviscapine, different degrees of renal injury improvement appeared. Compared with the BCG, the serum levels of Scr and BUN in the MCG increased to (89.92 ± 6.78) μmoL/Land (15.32 ± 4.53) mmoL/L. The differences were statistical significant (P < 0.01). Compared with the MCG, the serum levels of Scr and BUN in the Bre low-dose groups and Bre high-dose groups decreased significantly (P < 0.05). Compared with the BCG, the MDA levels in serum and in the renal cortex in the MCG significantly increased, while the SOD levels significantly decreased. Both the differences were statistically significant (P < 0.01). In the Bre low-dose groups and Bre high-dose groups, MDA levels in serum and in the renal cortex significantly decreased, while SOD and glutathione peroxidase levels in the renal cortex significantly increased, compared with the MCG; and the differences were statistically significant (P < 0.05). Conclusions: Breviscapine can reduce cisplatin-induced renal toxicity in mice and it's possible through inhibition of renal tubule cell lipid peroxidation and reduces the nephrotoxicity of cisplatin.

Therapeutic effect and mechanism of breviscapine on cisplatin-induced nephrotoxicity in mice

OBJECTIVE@#To observe the protective effect of breviscapine on mice with cisplatin-induced nephrotoxicity.@*METHODS@#Mice were given a single injection of cisplatin (8 mg/kg, i.p.); then, breviscapine was given to mice at 25 mg/kg and 50 mg/kg doses, respectively, once a day for seven days. Renal tissue structure was observed after animals were sacrificed. Blood urea nitrogen (BUN), serum creatinine (Scr), lipid peroxide (MDA) and superoxide dismutase (SOD) serum levels were detected; and MDA, glutathione peroxidase, and SOD levels in the renal cortex were detected.@*RESULTS@#Compared with the blank control group (BCG), the kidney pathological damage of mice in the model control group (MCG) was more severe. After applying different doses of breviscapine, different degrees of renal injury improvement appeared. Compared with the BCG, the serum levels of Scr and BUN in the MCG increased to (89.92 ± 6.78) μmoL/Land (15.32 ± 4.53) mmoL/L. The differences were statistical significant (P < 0.01). Compared with the MCG, the serum levels of Scr and BUN in the Bre low-dose groups and Bre high-dose groups decreased significantly (P < 0.05). Compared with the BCG, the MDA levels in serum and in the renal cortex in the MCG significantly increased, while the SOD levels significantly decreased. Both the differences were statistically significant (P < 0.01). In the Bre low-dose groups and Bre high-dose groups, MDA levels in serum and in the renal cortex significantly decreased, while SOD and glutathione peroxidase levels in the renal cortex significantly increased, compared with the MCG; and the differences were statistically significant (P < 0.05).@*CONCLUSIONS@#Breviscapine can reduce cisplatin-induced renal toxicity in mice and it's possible through inhibition of renal tubule cell lipid peroxidation and reduces the nephrotoxicity of cisplatin.

Alveolar bone thickness around maxillary central incisors of different inclination assessed with cone-beam computed tomography / 대한치과교정학회지

OBJECTIVE: To assess the labial and lingual alveolar bone thickness in adults with maxillary central incisors of different inclination by cone-beam computed tomography (CBCT). METHODS: Ninety maxillary central incisors from 45 patients were divided into three groups based on the maxillary central incisors to palatal plane angle; lingual-inclined, normal, and labial-inclined. Reformatted CBCT images were used to measure the labial and lingual alveolar bone thickness (ABT) at intervals corresponding to every 1/10 of the root length. The sum of labial ABT and lingual ABT at the level of the root apex was used to calculate the total ABT (TABT). The number of teeth exhibiting alveolar fenestration and dehiscence in each group was also tallied. One-way analysis of variance and Tukey's honestly significant difference test were applied for statistical analysis. RESULTS: The labial ABT and TABT values at the root apex in the lingual-inclined group were significantly lower than in the other groups (p < 0.05). Lingual and labial ABT values were very low at the cervical level in the lingual-inclined and normal groups. There was a higher prevalence of alveolar fenestration in the lingual-inclined group. CONCLUSIONS: Lingual-inclined maxillary central incisors have less bone support at the level of the root apex and a greater frequency of alveolar bone defects than normal maxillary central incisors. The bone plate at the marginal level is also very thin.

Increased L-arginine Production by Site-directed Mutagenesis of N-acetyl-L-glutamate Kinase and proB Gene Deletion in Corynebacterium crenatum / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>In Corynebacterium crenatum, the adjacent D311 and D312 of N-acetyl-L-glutamate kinase (NAGK), as a key rate-limiting enzyme of L-arginine biosynthesis under substrate regulatory control by arginine, were initially replaced with two arginine residues to investigate the L-arginine feedback inhibition for NAGK.</p><p><b>METHODS</b>NAGK enzyme expression was evaluated using a plasmid-based method. Homologous recombination was employed to eliminate the proB.</p><p><b>RESULTS</b>The IC50 and enzyme activity of NAGK M4, in which the D311R and D312R amino acid substitutions were combined with the previously reported E19R and H26E substitutions, were 3.7-fold and 14.6% higher, respectively, than those of the wild-type NAGK. NAGK M4 was successfully introduced into the C. crenatum MT genome without any genetic markers; the L-arginine yield of C. crenatum MT-M4 was 26.2% higher than that of C. crenatum MT. To further improve upon the L-arginine yield, we constructed the mutant C. crenatum MT-M4 proB. The optimum concentration of L-proline was also investigated in order to determine its contribution to L-arginine yield. After L-proline was added to the medium at 10 mmol/L, the L-arginine yield reached 16.5 g/L after 108 h of shake-flask fermentation, approximately 70.1% higher than the yield attained using C. crenatum MT.</p><p><b>CONCLUSION</b>Feedback inhibition of L-arginine on NAGK in C. crenatum is clearly alleviated by the M4 mutation of NAGK, and deletion of the proB in C. crenatum from MT to M4 results in a significant increase in arginine production.</p>

An investigation on status of health literacy and its influencing factors among residents in Qiandao Lake town / 预防医学

Objective To understand the status of health literacy of residents in Qiandao Lake town in order to complete the surveillance system.Methods A total of 484 residents aged 15 to 69 years old from 9 communities were selected using cluster random sampling method.Then the household interview was conducted.Results The overall level of health literacy of residents was 26.03%.As for the 4 health literacy related aspects including basic health knowledge,health lifestyle and behaviors,health related skill and health beliefs,the rates were 32.54% ,4.77% ,60.30% and 92.62%,respectively. The multivariate logistic regression analysis showed that the level of health literacy of residents was related to age and education.Conclusion The health education in Qiandao Lake town has got some achievements.

Efficacy and safety of the HAA regimen as induction chemotherapy in 236 de novo acute myeloid leukemia / 中华血液学杂志

<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>

Cause analysis of 280 case of fractures nonunion / 中国骨伤

<p><b>OBJECTIVE</b>To research many clinical data of nonunion cases and discover the reasons for low capacity of bone growth.</p><p><b>METHODS</b>From October 1999 to April 2009,the source material of 280 nonunion cases were conducted and followed up. The data of the study included 230 males and 50 females,with an average age of 39.4 years old ranging from 19 to 62 years. The fracture position was femur in 129 cases,tibia in 83 cases,humerus in 47 cases, feet radius bone in 21 cases, the ratio was 46:29.6:16.8:7.5. The survey included primary injury process,damage degree and the effect of first treatment,hospital level of first treatment,timing of surgery for the first time, the early callus growth conditions and whether there were obvious technical errors.</p><p><b>RESULTS</b>There were 129 femoral nonunion cases with complete data,121 cases derived from closed fractures, 8 cases from open fractures; 111 cases was aseptic nonunion. 90% of femoral aseptic nonunion had no obvious callus growth, 80% of first treatment performed intraday surgical internal fixation, 10% were undergone operation within three days and 90% was early surgery totally.</p><p><b>CONCLUSION</b>Low quality of bone callus growth is the main reason for current nonunion and the early surgical fixation has much to do with low quality of bone callus growth.</p>

Expression of BCL2L12 gene in de novo acute myeloid leukemia and its clinical implications / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To explore the expression of BCL2L12 gene and its clinical significance for de novo acute myeloid leukemia (AML).</p><p><b>METHODS</b>Real-time quantitative PCR (RQ-PCR) was employed to measure the expression of BCL2L12 gene in 134 patients with de novo AML. The results were correlated with clinical features of patients.</p><p><b>RESULTS</b>BCL2L12 gene transcript was determined for 134 AML patients and 49 healthy controls, with the median levels measured 0.1029 (0.0119-26.4090) and 0.2677 (0.0173-1.2858), respectively. There was a significant difference in the strength of BCL2L12 gene expression between patients and normal controls (P < 0.01). Those with lower BCL2L12 expression levels had a higher FLT3-ITD mutation rate compared with those with higher levels (27% vs. 5%, P = 0.036). Relapsed or refractory AML patients had lower expression compared with newly diagnosed patients (0.0873 vs. 0.1359, P = 0.014). There was no difference in overall survival (OS) between patients with higher and lower expression levels. However, for AML patients with a normal karyotype, the OS for those with lower expression was significant shorter (P = 0.037).</p><p><b>CONCLUSION</b>De novo AML patients have a lower level of BCL2L12 gene expression. AML patients with lower BCL2L12 expression have a higher FLT3-ITD mutation rate, and most of them are relapse or refractory patients. In addition, among patients with a normal karyotype, those with a lower BCL2L12 expression have a shorter OS. Therefore, expression of the BCL2L12 gene may be used as a prognostic marker for AML patients with a normal karyotype.</p>

Karyotypic analysis and prognosis for 41 patients with chronic myelomonocytic leukemia / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To analyze cytogenetic features of chronic myelomonocytic leukemia (CMML) patients and explore the relationship between cytogenetic characteristics and prognosis.</p><p><b>METHODS</b>Clinical and laboratory data of 41 CMML patients were analyzed.</p><p><b>RESULTS</b>The majority of CMML patients were middle-aged males. According to WHO classification, 17 (41.5%) patients were diagnosed as CMML-Ⅰ and 24 (58.5%) were diagnosed as CMML-Ⅱ. 14 (34%) of CMML patients harbored abnormal karyotypes and +8 was the most common. CMML-Ⅰpatients with abnormal karyotypes were older than those with normal karyotypes. CMML-Ⅱ patients with normal karyotypes had higher lymphocyte counts than those with abnormal karyotypes. Of 29 patients who had follow-up data, 26 died, with the median survival time being 4 (1-13) months. The median survival of patients with normal and abnormal karyotypes were 4.5 and 3.8 months, respectively (P=0.408). The median survival of CMML-Ⅰ patients with abnormal karyotypes was shorter than those with normal karyotypes (3 and 17 months, P=0.015), but no significant difference was found between the median survival of the two groups of CMML-Ⅱ patients (2.9 and 5.8 months, P=0.629).</p><p><b>CONCLUSION</b>+8 has been the most common abnormal karyotype in CMML patients. The abnormal karyotype can be regarded as an indicator of poor prognosis for CMML-Ⅰ patients. Regardless of their karyotypes, CMML-Ⅱ patients have even poorer prognosis.</p>

Clinical analysis on 15 acute myeloid leukemia patients with 11p15 abnormalities / 中华血液学杂志

<p><b>OBJECTIVE</b>To analyze the cytogenetic and clinical features of acute myeloid leukemia (AML) with 11p15 abnormalities and explore its influence on prognosis.</p><p><b>METHOD</b>The clinical and laboratory data of AML patients with 11p15 abnormalities from the First Affiliated Hospital of Zhejiang University from 1994 to 2010 were collected and their prognosis was analyzed.</p><p><b>RESULTS</b>15 (0.87%) out of 1725 de novo AML had abnormalities of 11p15, of which 6 cases involved t(7; 11), 2 had t(1; 11) and 2 had t(11; 12). And others manifested t(2; 11), t(11; 11), t(11; 14), del (11) or inv (11) respectively. The FAB type of 15 cases with 11p15 abnormalities were M2 (10 cases), M5 (3 cases), M1 (1 case) and M4 (1 case). ALL 6 cases with t(7; 11) were M2, 5 of them showed of Auer rods in myeloid blasts. 12 of 15 patients had received chemotherapy, and 7 patients obtained complete remission (CR), the median duration of CR was only 8 months (4-12 months); Of the 15 patients, 13 died, and the median overall survival (MS) was 11 months (2-19 months).</p><p><b>CONCLUSIONS</b>11p15 abnormalities is a rare recurring chromosomal aberration in AML of which the of with the most commonly seen is t(7; 11), which has its unique clinical and laboratory characteristics. AML patients with 11p15 abnormalities had a poor prognosis.</p>

Expression level of CDX2 gene in acute myeloid leukemia and its clinical significance / 中华血液学杂志

<p><b>OBJECTIVE</b>To explore the expression and clinical significance of Caudal-type homeobox transcription factor 2 (CDX2) gene in acute myeloid leukemia (AML) patients.</p><p><b>METHOD</b>Real time quantitative PCR (RQ-PCR) was used to test the expression level of CDX2 gene in 108 de novo AML patients and the clinical features of these patients were analyzed.</p><p><b>RESULTS</b>CDX2 gene transcript levels were detectable in bone marrow mononuclear cells from 108 AML patients and 7 healthy donors, the median expression level were 1179.44 (range 14.15 - 867 961.10) and 105.30 (range 22.30 - 453.11). There was a statistically significant difference in expression level of CDX2 gene between the AML patients and normal donor (P < 0.01). All 14 patients with FLT3-ITD(+) were in CDX2 gene higher expression group (P = 0.018), including 10 patients with normal karyotype. In the 83 treated AML patients (P = 0.046) and 57 higher WBC count (≥ 10×10(9)/L, P = 0.048) patients, the higher expression level of CDX2 gene was associated with lower complete remission (CR) rates.</p><p><b>CONCLUSIONS</b>Higher expression level of CDX2 gene was seen mostly in AML patients with FLT3-ITD mutation and with lower CR rates. CDX2 gene might be a prognostic molecular marker in AML patients with normal karyotype.</p>

Characteristics and outcome of chromosomal abnormalities in Ph negative cells of chronic myelogenous leukemia patients treated with tyrosine kinase inhibitors / 中华医学遗传学杂志

<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>

Expression and clinical significance of ID1 gene in acute myeloid leukemia / 中华血液学杂志

<p><b>OBJECTIVE</b>To explore the expression and clinical significance of ID1 gene in acute myeloid leukemia (AML) patients.</p><p><b>METHOD</b>Real-time quantitative PCR (RQ-PCR) was used to test the expression level of ID1 gene in 114 de novo adult AML patients, and the clinical features of these patients were analyzed.</p><p><b>RESULTS</b>ID1 gene transcript levels were detectable in BM mononuclear cells from 114 patients with AML, the median expression level of all samples was 8525 (range: 57 - 11 233 238). There was a statistically significant difference on expression level of ID1 gene among the three different cytogenetic prognosis groups, and the poor prognosis group (median: 36 840, range: 336 - 11 233 238) harbored the significantly higher level of ID1 gene than the intermediate prognosis group (Median: 6630, range: 66 - 1 840 798) (P = 0.006). The expression level of ID1 gene was positively associated with older age (age ≥ 60 years vs < 60 years, P = 0.002) and higher WBC count (WBC ≥ 10×10(9)/L vs < 10×10(9)/L, P = 0.005). Young patients (age < 60 years) who were not obtained the complete remission (non-CR) after the first cycle of chemotherapy harbored the high level of ID1 gene (Median: 9537 of non-CR vs 1268 of CR, P = 0.010).</p><p><b>CONCLUSIONS</b>High expression level of ID1 gene was mostly seen in AML patients with adverse cytogenetics and older age (age ≥ 60 years), and may be associated with poor prognosis of AML. ID1 gene might be a prognostic molecular marker of AML.</p>

Clinical study of Philadelphia chromosome-positive adult acute lymphoblastic leukemia / 中华血液学杂志

<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>