To explore the quality markers of Huangqin Qingre Chubi capsule in the treatment of rheumatoid arthritis based on network pharmacology combined with pharmacokinetics and target verification / 药学学报

As an effective prescription for the treatment of rheumatoid arthritis (RA), Huangqin Qingre Chubi capsule (HQC) is still blank in quality control. This study aims to explore quality markers (Q-markers) for HQC in the treatment of RA by integrating network pharmacology and pharmacokinetics. By constructing the visualization network of "pharmacodynamic ingredient-target-pathway", the potential Q-Marker of HQC treatment for RA was preliminatively predicted. A rat model of rheumatic heat obstruction syndrome collagene-induced arthritis (CIA) was established to elucidate the dynamic quantification law of pharmacodynamic components of HQC in the disease state of rats. To establish the inflammatory model of RA synovial fibroblasts (MH7A) induced by tumor necrosis factor-α (TNF-α) in vitro. The effects of active ingredients on protein expression of sphingosin kinase-1 (Sphk1) and p-SphK1 were detected. The network pharmacological results showed that baicalin, geniposide, luteolin, coixol and amygdalin were the important active components of HQC treatment for RA. Quantitative analysis results further verified the measurability of these five components. The expression of Sphk1 and p-SphK1 was significantly inhibited by geniposide and baicalin by Western blotting. The above studies determined that the above 5 components could be used as Q-markers in the treatment of RA by HQC. This experiment was approved by the Experimental Animal Ethics Committee of Anhui University of Chinese Medicine (approval number: AHUCM-rats-2021049). All procedures were conducted in strict accordance with the principles of animal use and care.

Systematic review and sequential analysis of Xuebijing Injection in treatment of systemic inflammatory response syndrome / 中国中药杂志

To systematically review the efficacy of Xuebijing Injection combined with western medicine in the treatment of systemic inflammatory response syndrome(SIRS). In this study, CBM, CNKI, Wanfang, VIP, PubMed and EMbase databases were retrieved for clinical randomized controlled trials on the effect of Xuebijing Injection combined with western medicine in the treatment of SIRS from the establishment of the database to July 31, 2020. After screening, Meta-analysis was conducted by RevMan 5.3 software, trial sequential analysis was conducted by TSA 0.9.5.10 beta software, and the evidence quality level was evaluated by GRADEprofiler 3.6.1 software. Meta-analysis showed that Xuebijing Injection combined with western medicine could reduce white blood cell count(MD=-2.32, 95%CI[-2.44,-2.21], P<0.000 01), C-reactive protein count(MD=-22.70, 95%CI[-29.61,-15.79], P<0.000 01), APACHE Ⅱ score(MD=-2.15, 95%CI[-2.43,-1.87], P<0.000 01), tumor necrosis factor alpha count(SMD=-1.23, 95%CI[-1.48,-0.99], P<0.000 01) and interleukin-6 count(SMD=-0.92, 95%CI[-1.15,-0.69], P<0.000 01), improve treatment efficiency(RR=1.39, 95%CI[1.23, 1.56], P<0.000 01), reduce incidence of multiple organ dysfunction(RR=0.47, 95%CI[0.35, 0.64], P<0.000 01) and mortality(RR=0.22, 95%CI[0.13, 0.37], P<0.000 01), which were better than western medicine treatment alone. Trial sequential analysis showed that in terms of reducing the incidence of multiple organ dysfunction and C-reactive protein count, the cumulative Z value passed through the traditional threshold, TSA threshold and expected information value, and reached the required number of cases. GRADE evaluation showed that the level of evidence was low or very low. According to the findings, Xuebijing Injection combined with western medicine is effective in treating SIRS. However, as the low quality of the included studies may affect the reliability of the conclusion, more high-quality studies shall be included for further verification in the future, so as to provide better suggestions for clinical medication.

The role of HIF-VEGF-Ang-2 signal transduction-mediated synovial angiogenesis in rheumatoid arthritis / 药学学报

Rheumatoid arthritis (RA) is an autoimmune disease with angiogenesis, inflammatory factor infiltration and joint destruction as the main pathological features. Angiogenesis promotes the development of RA and plays an important role in its pathogenesis. The hypoxia-inducible factor (HIF)-vascular endothelial growth factor (VEGF)-angiopoietin-2 (Ang-2) signal transduction is a critical pathway to induce synovial angiogenesis. Targeting HIF-VEGF-Ang-2 signal transduction to inhibit synovial angiogenesis is a promising approach for RA treatment. This article reviews the role and mechanism of HIF-VEGF-Ang-2 signal transduction-mediated synovial angiogenesis in RA, in order to provide a new target and strategy for RA treatment.

Study on vacuum drying process of extract paste of Huangqi Baihe Granules based on Box-Behnken design-response surface and G1-entropy method / 中草药

Objective To optimize the vacuum drying process of extract paste of Huangqi Baihe Granules (HBG) and evaluate the physical quality of powder. Methods With drying temperature, vacuum degree, and material thickness as independent variables, the comprehensive evaluating indexes of content of calycosin 7-O-β-D-glucopyranoside, hesperidin, crude polysaccharide, ethanol extraction amount, and drying rate as response values, Box-Behnken design-response surface methodology and G1-entropy method were used to optimize the vacuum drying process. The similarity of fingerprints between extract powder dried by the optimized technology and extract paste was compared. Additionally, the properties of powder were evaluated comprehensively with nine physical indicators, including relative homogeneity index, bulk density, tap density, interparticle porosity, compressibility, Hausner ratio, angle of repose, moisture content, and hygroscopicity. The physical fingerprint of powder were established to evaluate the quality consistency of different batches of extract powder. Results The optimal drying parameter was as follows: the drying temperature was 68 ℃, the vacuum degree was 0.07 MPa, the material thickness was 6 mm. Three verification experiments were carried out under these conditions and the average comprehensive evaluating indexes of vacuum drying was 91.05, which was close to the model prediction 91.87, and the relative error was 0.89%. Compared with the extract paste, the similarity of fingerprint of extract powder were more than 0.91. The similarity of chemical and physical fingerprint of three batches of extract powder were higher than 0.99. Conclusion The optimized vacuum drying technology of extract paste of HBG is stable and feasible.

Research progress of N-Myc roles in hematopoiesis and hematologic malignancies / 中国实验血液学杂志

N-Myc oncogene plays an important role in the process of hematopoietic cell proliferation and differentiation in embryos. Once the body suffers from hematologic malignancies, the expression of N-Myc would increase and significantly associate with disease progression. In this article the structure of N-Myc, the regulatory mechanism in the different hematopoietic lineages, the interaction in each signal pathways, the transgenic animal model of overexpression, and intervention by drugs are reviewed.

Mitochondria-mediated apoptosis induced by 5-aminolevulinic acid-based photodynamic therapy in HL-60 cells / 中国实验血液学杂志

This study was purposed to investigate the changes of mitochondrial membrane potential (MMP) and apoptosis-related gene Bcl-2 expression of HL-60 cells treated with 5-aminolevulinic acid-based photodynamic therapy (ALA-PDT). HL-60 cell line was used as a model and divided into 4 groups: ALA group, PDT group, ALA+PDT group and control group. The change of MMP was detected by flow cytometry with JC-1 (lipophilic cation 5, 5', 6, 6'-tetrachloro-1, 1', 3, 3'-tetraethyl-benzimidazol-carbocyanine iodide); the mRNA expression of Bcl-2 was determined by semi-quantitative RT-PCR and real-time PCR. The results demonstrated that MMP significantly decreased after treatment with ALA-PDT and the ratio of cells with disrupted MMP obviously increased in ALA+PDT group in time-dependence manner, as compared with control, ALA and PDT groups (P < 0.05), while no difference between ALA and PDT groups was found. The semi-quantitative RT-PCR and real-time PCR showed that the expression level of Bcl-2 was obviously down regulated at 2 h after ALA-PCT, further down-regulated at 4 h, and lasted in low level at 24 h. It is concluded that ALA-PDT-induced apoptosis of HL-60 cells is associated with its effect on MMP, that is ALA-PDT promotes cell apoptosis through effect on mitochondrial function.

Expression of ezrin in human non-small cell lung cancer and its relationship with metastasis and prognosis / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To explore the expression of ezrin protein in human non-small cell lung cancer (NSCLC) tissues and lung cancer cell lines, and the association between the expression of ezrin protein and the expression of E-cadherin and CD44V6 proteins.</p><p><b>METHODS</b>The expression of ezrin protein and mRNA in lung cancer cell lines was detected by RT-PCR and Western blotting. Ezrin, E-cadherin and CD44V6 were detected by immunohistochemical SP staining in tumor tissues from 150 lung cancer cases and in adjacent normal lung tissues from 30 patients. Furthermore, the expression of ezrin in 30 freshly-taken NSCLC tissues was also detected by Western blot.</p><p><b>RESULTS</b>The expression of ezrin protein and mRNA was up-regulated in highly metastatic human lung cancer. The positive rate of ezrin, E-cadherin and CD44V6 expression in the lung cancer was 61.3%, 54.0% and 58.7%, respectively. The up-regulation of ezrin expression was significantly correlated with lymph node metastasis, but not correlated with age, sex, tumor size, histological type, clinical TNM system and pathological grade. Western blot analysis showed that the level of ezrin in the NSCLC tissues was significantly higher than that in the normal tissues (t = 5.013, P < 0.01). Survival analysis showed that the 5-year survival rate of patients with negative ezrin expression was 29.3%, significantly higher than that of patients with positive ezrin expression (15.2%, χ(2) = 4.128, P = 0.042). Multivariate Cox regression analysis showed that ezrin expression (RR = 3.012, P = 0.047) and lymph node metastasis (RR = 4.827, P = 0.035) were significantly independent prognostic factors for patients with lung cancer. Furthermore, a negative correlation was observed between the expressions of ezrin and E-cadherin in lung cancer, and a positive correlation between the expressions of ezrin and CD44V6 in lung cancer.</p><p><b>CONCLUSIONS</b>Ezrin, E-cadherin and CD44V6 play an important role in the regulation of growth and meastasis of lung cancer. Combined detection of ezrin, E-cadherin and CD44V6 expression is helpful in evaluating the metastasis and prognosis of non-small cell lung cancer.</p>

Evaluation of the impact of R-CHOP chemotherapy on efficacy, safety and prognosis in newly diagnosed diffuse large B-cell lymphoma patients and its prognostic impact: a multicenter retrospective study with long term follow-up / 中华血液学杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy, safety and prognostic impact of rituximab plus CHOP (R-CHOP) regimen on patients with diffuse large B-cell lymphoma (DLBCL), to access the impact of R-CHOP on patients' prognosis and to compare that with CHOP regimen.</p><p><b>METHODS</b>Five hundred and seven newly diagnosed DLBCL patients were enrolled from Jan. 1, 2000 to May 1, 2010. Patients were administered with 6 cycles of CHOP or at least 4 cycles of R-CHOP treatments. Rituximab was administered intravenously on day 1 at a dose of 375 mg/m(2). The typical CHOP regimen include cyclophosphamide (750 mg/m(2), IV), doxorubicin (50 mg/m(2), IV) and vincristine (1.4 mg/m(2), IV, maximum 2 mg) and prednisone (60 - 100 mg, oral, day 3 - 7). The complete response (CR) rates, overall response (OR) rates, and side events of these 2 groups were compared.</p><p><b>RESULTS</b>Of the 411 analyzable patients, 224 received CHOP regimen and 187 received R-CHOP regimen. CR rate for R-CHOP group and CHOP group was 77.01% and 71.43%, respectively. OR rate in R-CHOP group was higher than that in the CHOP group (95.19% vs 87.95%, P = 0.007). The median follow-up time of R-CHOP group was 28.1 months vs that of 35.2 months in CHOP group. There was significant difference in progression free survival (PFS) and overall survival (OS) between 2 groups (P = 0.018 and 0.034, respectively). At the end of follow-up, the estimated median PFS in R-CHOP group had not been reached, while that was 84.8 months in CHOP group. The median OS in both groups had not yet been reached. The adverse events in R-CHOP group were similar with that in CHOP group.</p><p><b>CONCLUSIONS</b>R-CHOP is a safe and effective regimen for management of newly diagnosed DLBCL, with a better remission rate, PFS and OS.</p>

Expression of alternatively spliced human tissue factor in acute leukemia cells / 中国实验血液学杂志

The high expression of tissue factor (TF) is related to the coagulation disorder in acute leukemia. TF in blood circulation is mainly expressed in cells, microparticles (MP) and alternatively spliced human tissue factor (asHTF). To elucidate the role of TF in the coagulation disorder of acute myeloid leukemia (AML), RT-PCR was performed on 6 common AML cell lines NB4, HL-60, Kasumi-1, U937, K562 and THP-1. The results showed that only NB4 and U937 cells expressed baseline full-length TF and asHTF which were proved by sequencing. The flow cytometric detection, TF activity and TF antigen tests in NB4 and U937 cells revealed that the asHTF was expressed in trace amount and almost had no activity, while the TF antigen and activity in microparticles were significantly higher than that in asHTF. It is concluded that asHTF may play an unimportant role in the coagulation disorder of AML. Microparticle associated tissue factor (MP-TF) is the predominant source of TF activity released from AML cells.

Trend in the incidence and geographic variations of acute lymphoblastic leukemia in Shanghai, China from 2002 to 2006 / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Great advances have been made in the diagnosis, molecular pathogenesis and treatment of acute lymphoblastic leukemia (ALL) in the past decade. Due to the lack of large population-based studies, the recent trends in the incidence and geographic variations of ALL in Shanghai, China have not been well documented. To better understand the incidence and epidemiological features of ALL in Shanghai, we conducted a retrospective survey based on the database from the Shanghai Center for Disease Control and Prevention (CDC) and the medical records in all large-scale hospitals in Shanghai, especially those 30 major hospitals with hematology department.</p><p><b>METHODS</b>According to the data from Shanghai CDC, 544 patients, with a median age of 32 years (ranging 1.2 - 89 years), were diagnosed as de novo ALL from January 1, 2002 to December 31, 2006, and they were followed up until December 31, 2007.</p><p><b>RESULTS</b>The average annual incidence of ALL in Shanghai was 0.81/100 000. The incidence in men (0.86/100 000) was slightly higher than that in women (0.75/100 000). The age-stratified incidence showed that the incidence was 2.31/100 000 in patients ≥ 17 years old, 0.54/100 000 in those 18 - 34 years old, 0.46/100 000 in those 35 - 59 years old, and 0.94/100 000 in those ≥ 60 years old. Moreover, there were substantial geographic variations in the incidence of ALL, with the incidence in Chongming county, an island in the east of Shanghai city being 0.60/100 000, much lower than those of other districts. Both French-American-British (FAB) and World Health Organization (WHO) classification systems were applied in the present study. Eighty-eight patients were diagnosed as L1 (26.2%), 193 L2 (57.4%), and 55 L3 (16.4%). For 302 patients with immunophenotypic results, 242 were identified as B cell origin (80.1%), 59 as T cell origin (19.5%), and 1 as biphenotype (0.4%). The leukemia cells in 61 patients co-expressed one or two myeloid antigen (20.2%). For 269 patients with cytogenetic results, the incidences of t(9;22) in patients aged < 10, 11 - 17, 18 - 44, 45 - 59 and ≥ 60 years old were 4.2%, 11.4%, 19.2%, 23.1% and 5.3%, respectively.</p><p><b>CONCLUSION</b>Compared with the previous data, the incidence of ALL is increased in Shanghai, and has a geographic distribution characteristic.</p>

ShRNA against NSP4 gene inhibits the proliferation of bovine rotavirus in vitro / 病毒学报

Based on the NSP4 sequence of bovine rotavirus (BRV), the shRNA was designed and synthesized, and a shRNA recombinant lenti-virus vector RNAi-H1-89 was constructed. The recombinant RNAi-H1-89 Lenti-virus was packaged by transfecting the 293T cell with the recombinant vector RNAi-H1-89 and two helper plasmids using lipofectamine, and then used to infect MA104 cells. The MA104 cells were further infected with BRV strain G6 24h post-infection, with the LacZ shRNA recombinant lenti-virus as control. Thirty-six hours later, the CPE of the infected cells was observed under microscope, shRNA of NSP4 gene inhibited CPE in MA104 cell; the shRNA against NSP4 gene also inhibited NSP4 gene expression by RT-PCR, The virus titer in the cell culture supernatant was significant lower compared with the control group. The above results showed that RNAi-H1-89 against NSP4 gene could specifically silence NSP4 gene expression, and inhibit the proliferation of BRV.

An epidemiological survey of acute lymphocytic leukemia from 2002 to 2006 in Shanghai / 中华血液学杂志

<p><b>OBJECTIVE</b>To analyse the epidemiological data of acute lymphoblastic leukemia (ALL) in Shanghai.</p><p><b>METHODS</b>ALL cases in Shanghai from 2002 to 2006 were retrospectively investigated.</p><p><b>RESULTS</b>All together there were 544 newly diagnozed ALL cases. The yearly incidence of ALL was 0.81/10(5), which was slightly higher in men (0.86/10(5)) than in women (0.75/10(5)). The age-stratified incidence showed 2.31/10(5) in patients (pts) </= 17y, 0.54/10(5) in 18 - 34 y, 0.46/10(5) in 35 - 59 y, and 0.94/10(5) in pts > 60 y. The incidences in Chongming County was 0.60/10(5), being the lowest in all districts. The morphological types of ALL was L(1) (26.2%), L(2) (57.4%) and L(3) (16.4%); the immunophenotype was B (80.1%) and T (19.5%). The incidence of ALL with myeloid antigen expression was 20.2%. Genetic examination revealed that chromosome aberration of t(9;22) was the most common one.</p><p><b>CONCLUSIONS</b>The incidence of ALL in Shanghai is 0.81/10(5). Compared with the national standard (1986 - 1998), the incidence in adolescents is obviously increased. Chongming County has the lowest incidence, indicating a role of environment factor in ALL incidence.</p>

Research on mechanism of chloroquine phosphate-induced U937 cell apoptosis / 上海第二医科大学学报

Objective To observe the effects of chloroquine phosphate on apoptosis of leukemic cell line U937, and investigate whether chloroquine phosphate induces leukemic cell apoptosis by normalizing protein PNAS-2's abnormal subcellular location. Methods Chloroquine phosphate of different concentrations were added into culture fluid of leukemic cell line U937 at logarithmic phase. MTr was used to measure cell proliferation, flow cytometry and laser confocal microscopy were applied to detect cell apoptosis, and immunofluorescence technology was employed to observe the effects of chloroquine phosphate on the changes of subcellular location of protein PNAS-2. Results Apoptosis of leukemic cell line U937 was significantly induced by 50 μg/mL chloroquine phosphate, and subcellular location of protein PNAS-2 was changed. Conclusion Chlorequine phosphate can induce apoptosis of leukemic cell line U937, and the mechanism may be related to the normalization of PNAS-2's abnormal subcellular location in U937 cell line. Chloroquine phosphate has the potential to be used in leukemic therapy.

Preparation and identification of monoclonal antibody against PNAS-2 protein / 中国实验血液学杂志

This study was purposed to prepare and primarily identify the specific monoclonal antibodies (McAbs) against the apoptosis related protein PNAS-2 so as to provide the essential tool for study of PNAS-2 function. The McAbs against PNAS-2 were prepared via the immunization of mice, cell fusion and cloning using synthetic peptide of PNAS-2 as immunogen; the specificity, titer and subtype of McAb were detected by Western blot, ELISA and immunofluorescence. The results showed that the stable hybridoma cell line S-31-7 producing McAbs against PNAS-2 protein was successfully obtained. The immunoglobulin of the McAb was identified to be IGg1lambda. The titer of ascetic fluid fled McAb were 1:8,000. A single specific band with 28 kD was shown in Western blot test, and the antigen recognized was present in cell cytoplasm by immunofluorescence. In conclusion, the obtained McAb against PNAS-2 displays strong specificity and high titer, which may be applied to the advanced research on PNAS-2 protein.

Overview of chronic myelogenous leukemia and its current diagnosis and treatment patterns in 15 hospitals in China / 中华血液学杂志

<p><b>OBJECTIVE</b>To explore demographic characteristics, current diagnosis and treatment patterns of chronic myelogenous leukemia (CML) patients in China.</p><p><b>METHODS</b>Data of hospitalized CML patients in 2005 whole year and outpatient information (July 1 through September 30, 2006) from 15 hospitals throughout China were analyzed.</p><p><b>RESULTS</b>A total of 1824 CML cases were analyzed, including 722 inpatients and 1102 outpatients. The male/female ratio was 1.78:1. The median age at diagnosis was 40.02 (2.45 - 83.29) years old, 90.41% of the patients were diagnosed at chronic phase. Proportion of accelerated phase or blast crisis patients increased to 21.66% during study period. 93.20% of the patients received blood routine and bone marrow morphologic examination at diagnosis and in monitoring; 70.29% were performed cytogenetic analysis and 51.54% performed molecular measurement in addition. The most common therapy for CML treatment was hydroxycarbamide. The proportion of patients treated with imatinib and interferon was 37.45% and 25.55%, respectively. Of 722 inpatients, 164 (22.72%) received hemotopoietic stem cell transplantation (HSCT). The proportions of accelerated phase and blast crisis patients treated with imatinib were 48.28% and 48.42%, respectively, being significantly higher than that of chronic phase patients (35.9%) (P < 0.05). The mean imatinib dosage administered in the three phases patients did not differ significantly. Imatinib resistance rates were 6.87% and 16.28% for outpatient and inpatient, respectively. In the outpatient group, the primary resistance to imatinib occurred comparably to the secondary resistance (68.75%), while primary resistance was predominant in inpatient group (65.71%). The intolerance rates of imatinib for outpatient and inpatient were 3.21%, 11.63%, respectively. The majority of patients treated with imatinb were not monitored in time: 63.38% patients evaluated hematologic response after 3 months of treatment, proportions of patients received cytogenetic examination after 6 months and 12 months of treatment were 41.41% and 27.35%, respectively. Mean cost for HSCT was 213 092 +/- 125 890 RMB.</p><p><b>CONCLUSIONS</b>CML in China tends to afflict younger population than in Western countries. Most patients were diagnosed in the chronic phase. Due to restriction of financial support, only one third of CML patients were treated with imatinib, and the majority of the treated were not monitored in time. Clinicians should pay attention to resistance and intolerance to imatinib treatment in accelerated phase or blast crisis patients.</p>

Expression spectra of apoptosis-related gene pnas-2 / 中国实验血液学杂志

To explore the expression spectra of apoptosis-related gene pnas-2 in normal tissues and acute leukemia (AL) patient tissues, the expressions of pnas-2 gene in tissues including heart, brain, placenta, lung, liver, skeletal muscle, kidney, pancreas, spleen, lymph node, thymus, leukocyte, bone marrow and fetal liver were detected by Northern blot. The expressions of pnas-2 in samples including 44 de novo, 9 non-CR, 27 CR and 12 relapsed AL patients were measured by real-time RT-PCR and Northern blot, and the expression levels of pnas-2 in normal and tumor tissues from 31 patients with malignancies were also detected. The results showed that pnas-2 was not expressed in the most tissues except in placenta. The results of real-time PCR indicated that pnas-2 expressions in samples of de novo, non-CR and relapsed patients ware significantly higher than that in CR, tumor tissues and normal tissues. In serial monitoring of 7 AL patients, the expression level of pnas-2 was high at first visit examination, but remarkably decreased after remission, and the pnas-2 expression level increased again when relapsed. It is concluded that the pnas-2 is specifically up-regulated in acute leukemia patients, which might be an oncogene and participate in leukemogenesis.

Polymorphisms of CYP3A5 gene in acute leukemia patients and their role in chemotherapy and prognosis / 中国实验血液学杂志

The objective of study was to investigate the role of the polymorphisms and protein expression of CYP3A5 gene in the therapy and prognosis of acute leukemia (AL) patients, the polymorphisms of CYP3A5 gene and the expression of protein CYP3A5 were detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and immunohistochemistry method respectively. The results showed that there were three CYP3A5 genotypes in the 88 cases, namely CYP3A5*1/*1, CYP3A5*1/*3 and CYP3A5*3/*3 with frequencies of 26%, 50% and 24%, respectively. There were no significant differences in clinic data between the three groups, but the expressions of CYP3A5 of three groups were (36.6+/-19.2)%, (7.8+/-9.2)%, (0.5+/-0.9)%, the OS were (11.6+/-2.1) months, (30.5+/-12.2) months, (52.3+/-8.5) months, and the DFS were (7.5+/-1.8), (27+/-15.8), (52.3+/-8.1) months, respectively (p<0.05). It is concluded that the polymorphism of CYP3A5 gene is not related with the morbidity of AL, but closely associated with the expression of CYP3A5 in AL patients, and the latter are closely associated with the chemotherapeutic effect and prognosis. CYP3A5 genotype may be used as a new predictor to the chemotherapeutic effect and prognosis in AL cases.

Correlation between expression of apoptosis-related gene pnas-2 and leukemia / 中国实验血液学杂志

The study was purposed to explore the correlation between apoptosis-related gene pnas-2 and leukemia. The RT-PCR was performed to detect the expression levels of pnas-2 gene in NB4, K562, U937 cells before and after treatment with AS(4)S(4), and to analysis the expression change of pnas-2 gene in bone marrow cells from patients with acute leukemia before and after chemotherapy. The results showed that the expression of pnas-2 gene in arsenic sulfide treated NB4 cells was down regulated in time-dependent manner, but the same outcome in K562 and U937 cells after being treated with AS(4)S(4) was not found. The positive expression rate of pnas-2 in cells from untreated patients with acute leukemia was 100%, and was significantly higher than that in normal control group. After chemotherapy, the expression was negative in complete remission patients, whereas in no-remission patients there were no significant differences of expression of pnas-2 before and after treatment. It is concluded that the pnas-2 gene may be closely related with apotosis of arsenic sulfide treated APL cells, and may consider as a molecular biological remission marker in acute leukemia.

Effect of daunorubicin and cytarabine on cell line NB4 / 中华血液学杂志

<p><b>OBJECTIVE</b>To explore whether daunorubicin (DNR) combined with cytosine arabinoside (Ara-C) and DNR alone have similar effect on acute promyelocytic leukemia (APL) cell line NB4 and acute myeloblastic leukemia cell line HL-60 in vitro.</p><p><b>METHODS</b>Cell morphology, cells viability, and cell apoptosis (Annexin-V by flow cytometry assay) were analysed.</p><p><b>RESULTS</b>After incubation with DNR plus Ara-C for 24 hours,NB4 cell viability [(36.75 +/- 3.82)%] (n = 6) and cell apoptosis rate [(21.24 +/- 5.82)%] (n = 3) did not change significantly compared to that treated with DNR alone for 24 hours [(35.73 + 6.28 )%, (22.55 +/- 3.26)%, respectively] (P > 0.05). However, HL-60 cell viability [(67.17 +/- 2.07)%] and cell apoptosis rate [(48.05 +/- 0.92)%] changed significantly in DNR plus Ara-C group compared with DNR alone [(63.31 +/- 1.80)% ,(41.51 +/- 0.89)%, respectively] (P < 0.01 and < 0.05, respectively).</p><p><b>CONCLUSION</b>DNR plus Ara-C and DNR alone have similar effect on NB4 cells, but have different effect on HL-60 cells.</p>

The changes of mRNA expression of telomerase subunits induced by Ara-C in HL-60 cells / 中国癌症杂志

Background and purpose:Ara-C is one of the most effective and common agents in the treatment of acute nonlyphocytic leukemia. Telomerase is a unique complex of ribonucleoprotein. It plays an important role in the pathogenesis and development of cancer. In this study, we investigate the changes of mRNA expression of telomerase subunits in HL-60 cells induced by Ara-c and try to come up with a theory that could help to assess the efficacy of Ara-C. Methods:The combinations of various Ara-C concentration and the incubation time were used to treat HL-60. The ratios of apoptotic cell to necrosis cell were determined by flow cytometry and the expressions of telomerase subunits mRNA were evaluated by RT-PCR.Results:① There was no influence on transcription of telomerase subunits gene after HL-60 cells was cultured with 0~0.2ug/ml Ara-C for 12 hours;② 2ug/ml and 10ug/ml of Ara-C could down regulate the expression of hTERT from 0.80+0.07 to 0.50+0.04 and 0.39+0.03, not hTR and hTP1;③ with longer incubation with 10ug/ml of Ara-C, the percentage of apoptosis could be increased. The maximal induction of apoptosis (18.16+4.25%) could be reached at 12hrs treatment of Ara-C, then gradually decreased later on. The rate of necrosis increased with time, the maximal percentage(57.94+12.03%) of necrosis was observed at 48hrs of incubation time with drug. The mRNA level of hTERT gene also decreased along with the cultured time , the lowest value (0.18+0.03) has been documented at 48hrs time point, but not hTR、TP1.Conclusions:① Ara-C could down-regulate the expression of hTERT mRNA in a dose-and time-dependent manner, but not hTR、hTP1;② There might be no relationship between the percentage of apoptosis induced by Ara-C apoptosis and the expression of telomerase hTERT gene mRNA, but a close relationship between necrosis and the expression of hTERT mRNA has been found.