Joint association of sleep duration and physical activity with cognitive performance among Chinese adults: an analysis of nationally representative survey data.

Background: Although previous studies have identified that both physical activity and sleep problems are independently associated with decreased risk of cognitive function. However, the joint association of physical activity and sleep duration with cognitive function was rarely studied. Methods: A total of 21,128 participants who had records from the China Family Panel Studies (CFPS) in 2018 were included in this study. Linear regression was used to examine the associations of joint between physical activity and sleep duration with cognitive function in the nationally representative survey data. Results: Compared with individuals reporting 150 min/week or more of activity, those reporting no physical activity had a 116% higher risk of getting lower vocabulary scores (coefficient: -1.16, 95% CI: -1.55 ~ -0.78) and a 61% higher risk of getting lower mathematics scores (coefficient: -0.61, 95% CI: -0.78 ~ -0.44). Compared with those who slept for 7-10 h/day, those who slept more than 10 h/day had the lower vocabulary scores (coefficient: -1.34, 95% CI: -1.86 ~ -0.83) and mathematics scores (coefficient: -0.68, -0.94 ~ -0.42). The results of joint analysis showed that the adjusted coefficient for vocabulary scores were - 2.58 (95% CI, -3.33 ~ -1.82) for individuals reporting no physical activity and sleeping for 10 h/day, and - 1.00 (95% CI, -1.88 ~ -0.12) for individuals reporting more than 150 min/week and sleeping for 10 h/day, compared with those who reported a sleep duration for 7-10 h/day and more than 150 min/week physical activity, Any level of physical activity combined with longer sleep duration (≥10 h/day) was associated with a higher risk of getting low mathematics scores. Conclusion: Appropriate sleep and sufficient physical activity together may have amplified association on cognitive performance, highlighting the importance of a comprehensive healthy lifestyle.

[Efficacy of Different Doses of Daunorubicin Induced Chemotherapy in Patients with Newly Diagnosed Primary Acute Myeloid Leukemia Under 65 Years Old].

OBJECTIVE: To compare the efficacy and safety of different doses of daunorubicin combined with a standard dose of cytarabine as induction chemotherapy in newly diagnosed primary acute myeloid leukemia (AML) patients. METHODS: The clinical data and outcome were retrospectively analyzed in 86 newly diagnosed primary AML patients who were under 65 years old and treated with daunorubicin combined with cytarabine (DA regimen) at West China Hospital of Sichuan University from January 2017 to June 2019. Patients were divided into 2 groups based on the dose of daunorubicin they received, 35 cases in the escalated-dose group ï¼»75 mg/(m2·d)ï¼½ and 51 cases in the standard-dose group ï¼»60 mg/(m2·d)ï¼½. And then the effects of different doses of daunorubicin on complete remission (CR) rate, minimal residual disease (MRD)-negative CR rate, relapse-free survival (RFS), overall survival (OS), and adverse events were analyzed. RESULTS: Median follow-up time of all the patients was 15 months. The CR rate and MRD- CR rate of the escalated-dose group was 88.5% and 71.4%, respectively, which were higher than 64.7% and 41.2% of the standard-dose group (P=0.029, P=0.008). The estimated 2-year RFS of the escalated-dose group was 68.4%, which was higher than 38.5% of the standard-dose group (P=0.015), but estimated 2-year OS showed no statistically significant difference (77.1% vs 66.7%, P=0.059), as well as grade 3－4 adverse events. The escalated dose of daunorubicin had prolonged RFS (13 months vs not reached, P=0.022) and OS (23 months vs not reached, P=0.029) in the FLT3-ITD－ AML patients. CONCLUSION: The escalated dose of daunorubicin can induce higher complete remission rate, deeper remission and longer duration of remission without increasing adverse events in newly diagnosed primary AML patients.

Bendamustine treatment of Chinese patients with relapsed indolent non-Hodgkin lymphoma: a multicenter, open-label, single-arm, phase 3 study.

BACKGROUND: Bendamustine was approved in China on May 26th, 2019 by the National Medical Product Administration for the treatment of indolent B-cell non-Hodgkin lymphoma (NHL). The current study was the registration trial and the first reported evaluation of the efficacy, safety, and pharmacokinetics of bendamustine in Chinese adult patients with indolent B-cell NHL following relapse after chemotherapy and rituximab treatment. METHODS: This was a prospective, multicenter, open-label, single-arm, phase 3 study (NCT01596621; C18083/3076) with a 2-year follow-up period. Eligible patients received bendamustine hydrochloride 120 mg/m2 infused intravenously on days 1 and 2 of each 21-day treatment cycle for at least six planned cycles (and up to eight cycles). The primary endpoint was the overall response rate (ORR); and secondary endpoints were duration of response (DoR), progression-free survival (PFS), safety, and pharmacokinetics. Patients were classified according to their best overall response after initiation of therapy. Proportions of patients in each response category (complete response [CR], partial response [PR], stable disease, or progressive disease) were summarized along with a two-sided binomial exact 95% confidence intervals (CIs) for the ORR. RESULTS: A total of 102 patients were enrolled from 20 centers between August 6th, 2012, and June 18th, 2015. At the time of the primary analysis, the ORR was 73% (95% CI: 63%-81%) per Independent Review Committee (IRC) including 19% CR and 54% PR. With the follow-up period, the median DoR was 16.2 months by IRC and 13.4 months by investigator assessment; the median PFS was 18.6 months and 15.3 months, respectively. The most common non-hematologic adverse events (AEs) were gastrointestinal toxicity, pyrexia, and rash. Grade 3/4 neutropenia was reported in 76% of patients. Serious AEs were reported in 29 patients and five patients died during the study. Pharmacokinetic analysis indicated that the characteristics of bendamustine and its metabolites M3 and M4 were generally consistent with those reported for other ethnicities. CONCLUSION: Bendamustine is an active and effective therapy in Chinese patients with relapsed, indolent B-cell NHL, with a comparable risk/benefit relationship to that reported in North American patients. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, No. NCT01596621; https://clinicaltrials.gov/ct2/show/NCT01596621.

The derived neutrophil-lymphocyte ratio and the neutrophil-lymphocyte ratio are related to poor prognosis in Hodgkin lymphoma patients.

INTRODUCTION: The inflammatory and immune cells have an important impact on Hodgkin lymphoma (HL). The derived neutrophil-lymphocyte ratio (dNLR) has been confirmed to have a similar prognostic value as the neutrophil-lymphocyte ratio (NLR) in many kinds of tumors, but it has not been explored as a prognostic marker for Hodgkin lymphoma patients. OBJECTIVE: The aim of the study is to evaluate the prognostic value of dNLR and NLR in HL. METHODS: This retrospective study included 213 newly diagnosed HL patients from 2008 to 2019. Then, the prognostic significance of dNLR and NLR in these patients was evaluated. Meanwhile, subgroup analyses based on the Ann Arbor stage and histotype were also carried out. Finally, propensity score matching was used to reduce selection bias. RESULTS: Patients with dNLR ≥ 2.1 showed shorter overall survival (OS) (P = 0.006). Also, patients with NLR ≥ 3.0 showed worse OS (P = 0.005) and progression-free survival (PFS) (P = 0.031). These results were also found in patients with early-stage and mixed cellularity subtype HL. Besides, high dNLR represented an independent prognostic marker for OS and high NLR remained an independent prognostic factor for OS and PFS on multivariable analysis. CONCLUSION: Elevated dNLR and NLR were related to worse survival in HL patients. For the first time, the dNLR has shown the potential to be a new prognostic factor for patients with HL.

MicroRNA-184 Modulates Human Central Nervous System Lymphoma Cells Growth and Invasion by Targeting iASPP.

Central nervous system lymphoma (CNSL) remains a diagnostical and therapeutical challenge. MiRNAs post-transcriptionally regulate expression of targeted mRNAs through binding to their 3' UTR to inhibit their translation or promote their degradation. Oncoprotein inhibitory member of the ASPP family (iASPP), a key inhibitor of tumor suppressor p53, has been reported to play oncogenic role in cancers. Our present study was aimed to determine whether the miR-184/iASPP axis is involved in the proliferation and invasion of CNSL. A reduced level of miR-184 was observed in CNSL tissues. Exogenous miR-184 inhibited cell survival and invasion, as well as the tumor volumes, while miR-184 inhibition could reverse this process. The RNA and protein levels of iASPP were significantly inhibited by miR-184, and the 3' UTR of iASPP was shown to be a target of miR-184. The expression of iASPP was up-regulated in CNSL tissues, compared to that of the normal brain tissues. The inhibition of iASPP by shRNA iASPP significantly repressed CNSL cells' proliferation and invasion, and reduced the volume of the tumor. Besides, iASPP overexpression could partly restore the suppressive effect of miR-184 on CNSL cell proliferation and invasive capability. We also revealed that miR-184/iASPP axis regulated the proliferation and invasion via PI3K/Akt signaling pathway, which presents a novel potential therapy for intervention of CNSL. Taken together, our findings revealed the detailed role of the miR-184/iASPP axis in CNSL and this axis might modulate the proliferation and invasion of CNSL via regulating the PI3K/Akt signaling pathway. J. Cell. Biochem. 118: 2645-2653, 2017. © 2017 Wiley Periodicals, Inc.

Development-associated immunophenotypes reveal the heterogeneous and individualized early responses of adult B-acute lymphoblastic leukemia.

B cell acute lymphoblastic leukemia (B-ALL) exhibits phenotypes reminiscent of normal stages of B-cell development. As demonstrated by flow cytometry, the immunophenotypes are able to determine the stages of B cell development. Multicolor flow cytometry (MFC) is more accurate at identifying cell populations. In this study, 9-color panels, including CD10, CD19, CD20, CD22, CD34, CD79a, CD179a, and IgM, which are sequentially expressed during B cell development, were designed to detect the leukemia cell subpopulations in adult B-ALL patients. In 23 patients at diagnosis, 192 heterogeneous subpopulations of leukemia cells were detected. Compared with their counterparts at diagnosis and after the 1st course of induction therapy, the responses of the subpopulations were also heterogeneous. In the CD10 population, the residual B cell subpopulations in the BCR/ABL patients were obviously reduced compared to those in the BCR/ABL patients. New subpopulations were detected in 22 of 23 patients and were primarily located in the CD34CD10 populations. Subpopulations of clonal evolution were heterogeneous after induction therapy. Our results suggest that the subpopulations in B-ALL patients should be dynamically monitored by development-associated immunophenotyping before, during, and after induction therapy and to predict the prognosis of the disease.

[Construction of Recombinant Adenovirus Vector with Human/Mouse Interferon Gene and Its Transfection into Human Umbilical Cord Mesenchymal Stem Cells].

OBJECTIVE: Construction and identification of recombinant adenovirus vector with human/mouse interferon (IFN-gamma) and effectively transfection into human umbilical cord mesenchymal stem cells (HUMSCs). METHODS: IFN-gamma gene of human/mouse were amplified from the plasmid by polymerase chain reaction (PCR) and then inserted into the plasmid pDC316 to generate pDC316-IFN-gamma. After being confirmed by restriction enzyme digestion and DNA sequencing, the DNA encoding IFN-gamma in the new structure were inserted into the vector of recombinant plasmid adenovirus and confirmed by restricition enzyme digestion. Then the human embryonic kidney cell line 293 were transfected with confirmed Ad-IFN-gamma, and the recombinant adenovirus were amplified, and the virus titer were detected using 50% tissue culture infective dose (TCID50) assay. The expression of the green fluorescent protein (GFP) and IFN-gamma were detected by fluorescent microsope and Western blot and ELISA after the recombinant adenovirus transfected HUMSCs. RESULTS: The recombinant adenovirus Ad-hIFN-gamma were constructed successfully, and amplified with titer of 1.6 x 10(10) IU/mL. The titer of Ad-mIFN-gamma was 1.0 x 10(10) IU/mL and the titer of Ad-GFP was 1.0 x 10(9) IU/mL. The green fluorescence proteins could be observed under fluorescent microscope in HUMSCs 24 h after transfection and with a stronger degree after 72 h, and IFN-gamma expression in HUMSCs were confirmed by Western blot and ELISA. CONCLUSION: Construction and identification of recombinant adenovirus vector of human/mouse IFN-ygamma and effectively transfection of HUMSCs were successful.

[Imbalance of Th17 and Treg cells in peripheral blood from multiple myeloma patients].

OBJECTIVE: To investigate the ratio of Th17 cells and CD4⁺CD25⁺Foxp3⁺ regulatory T (Treg) cells in peripheral blood from patients with multiple myeloma (MM) and explore its pathological effects. METHODS: 70 MM patients were divided into three groups: newly diagnosed group (n=30), plateau stage group (n=23) and relapsed/refractory group (n=17). The controls consisted of 20 healthy donors. The frequencies of Th17 and Treg cells were detected by flow cytometry. RESULTS: Compared with controls [(0.72±0.33)%] and plateau stage group [(0.74±0.29)%], frequencies of Th17 cells were higher in newly diagnosed group [(1.62±0.65)%] and relapsed/refractory group [(1.45±0.51)%], respectively (P<0.05). Compared with controls [(2.33±0.90)%] and plateau stage group [(1.69±0.70)%], frequencies of Treg cells were significantly lower in newly diagnosed group [(0.55±0.23)%] and relapsed/refractory group [(0.82±0.54)%], respectively (P<0.05). The ratios of Th17/Treg in newly diagnosed group and relapsed/refractory group were higher than those in controls (P<0.05). There were no differences of the frequencies of CD3⁺CD4⁺ T cells and Th17 cells between plateau stage group and controls. The frequencies of Treg cells were significantly lower in plateau stage group than that in controls (P<0.05), and the ratio of Th17/Treg was significantly higher in plateau stage group than that in controls (P<0.05). CONCLUSION: The remarkable abnormality of T cells subsets was reduction of CD4⁺ T cells in MM. Higher frequency of Th17 and lower ratio of Treg could lead to imbalance of Th17/Treg, which may play a critical role in the pathogenesis of MM.

MicroRNAs as biomarkers for hepatocellular carcinoma: a diagnostic meta-analysis.

BACKGROUND: Numerous studies reported various microRNAs (miRNAs) could be novel serum biomarkers for hepatocellular carcinoma (HCC). However, the diagnostic ability of different miRNA biomarkers varies among the reports. In this paper, we made a meta-analysis about the diagnostic accuracy of miRNAs for HCC. METHODS: We systematically searched The Cochrane Central Register of Controlled Trials, MEDLINE, Pub Med, EMBASE, the Chinese Biomedical Literature Database, the China Academic Journals Full-text Database, and the Chinese Scientific Journals Database for potential studies. Studies were included if they were related to miRNAs and HCC and reported diagnostic outcomes. Diagnostic values analysis was used to summarize the overall test performance of miRNAs. RESULTS: Eight studies were included in this meta-analysis. The ranges of the diagnostic value of miRNAs for HCC were as follows: sensitivity was 0.72 - 0.98, pooled sensitivity was 0.87; specificity was 0.76 - 1.00, pooled specificity was 0.90; positive likelihood ratio was 3.52 - 97.45, pooled positive likelihood ratio was 8.70; negative likelihood ratio was 0.02 - 0.31, pooled negative likelihood ratio was 0.13; and diagnostic odds ratio was 19.06 - 2,646.00, pooled diagnostic odds ratio was 86.69. CONCLUSIONS: MiRNAs showed high accuracy in identifying HCC, and could be a useful screening tool for diagnosing HCC patients.

[COX-2 inhibitor celecoxib can suppress the proliferation of FLT3-ITD positive acute myeloid leukemia cells with prominent down regulation of MEK/MCL-1 expression in vitro].

The purpose of this study was to investigate the effects of Celecoxib on the proliferation of the FLT3-ITD positive and negative acute myeloid leukemia cells and its mechanism. The proliferation inhibition effect of Celecoxib with different doses on the FLT3-ITD positive cells MV4-11 and the FLT3-ITD negative K562 cells was detected by CCK-8 method, the cell apoptosis was determined by flow cytometry, and the MEK, Mcl-1, pAKT expression was tested by Western blot. The results showed that Celecoxib inhibited the proliferation of both MV4-11 and K562 cells, but the IC50 for MV4-11 was (29.14 ± 2.4) µmol/L, which was significantly lower than that of K562 cells (39.84 ± 1.0) µmol/L (P < 0.05); The induced apoptosis rate of Celecoxib at 20-80 µmol/L on MV4-11 was not observed, but there was apparent influence on K562 at the same concentration. Western blot showed that Celecoxib down-regulated the expression of MEK and Mcl-1 but did not change the expression of pAKT obviously on MV4-11 cells, while the expression of Mcl-1 was reduced a little, but no obvious change were found in the expression of MEK and pAKT on K562 cells. It is concluded that the Celecoxib can inhibit the proliferation of FLT3-ITD positive AML cells distinctly, and the potential mechanism may be related to the inhibition of the MEK/Mcl-1 signaling pathway.

A simple, fast correction method of triglyceride interference in blood hemoglobin automated measurement.

BACKGROUND: To establish a reliable correction method for automated hemoglobin (HGB) measurement by minimizing the interference from blood high triglyceride (TG). METHODS: Fifty whole blood samples and 50 plasma samples containing variable TG concentrations were used to determine the centrifugation speed and time. Complete blood cell counts (CBCs) were performed by an automated hematology analyzer for 102 blood samples, in which high-level TG were artificially added. The same blood samples were centrifuged at low -speed to separate the plasma from blood cells. Then the plasma was analyzed by the same analyzer. By using the two CBC results, a correction formula was established to calculate the corrected HGB, mean corpuscular hemoglobin (MCH) and mean corpuscular hemoglobin concentration (MCHC) values. Comparisons were also made of HGB, MCH, and MCHC values before and after correction of in-patient individuals who received intralipid and developed lipemia. RESULTS: The percentage differences between the corrected and true values of HGB, MCH and MCHC were -0.28%, 0.06%, and -0.31%, respectively. The correlation coefficients of corrected values versus true values of HGB, MCH, and MCHC were 0.989, 0.935, and 0.717, respectively. This correction method was also effective for native lipemic samples. CONCLUSION: High blood TG level can cause blood turbidity and erroneously high HGB results by hematology analyzers commonly used in clinical laboratories. Adding a simple step of low-speed centrifugation and measurement of HGB in the plasma fraction allows a quick correction of HGB measurement in lipemic blood samples.

[Ratio balance of Th17 and Treg cells in peripheral blood of patients with chronic lymphocytic leukemia].

This study was purposed to investigate the ratio of Th17 cells and CD4(+)CD25(+)Foxp3(+) regulatory T (Treg) cells in peripheral blood of patients with chronic lymphocytic leukemia (CLL) and to explore their roles in the pathogenesis and clinical diagnosis. Based on the number of peripheral lymphocytes and treatment condition, the CLL patients were divided into 2 groups: untreated group (n = 30) and remission group (n = 15), the healthy control group (n = 20) was set up as well. The frequencies of Th17 and Treg cells of all cases were detected by flow cytometry (FCM). The results showed that frequencies of CD3(+)CD4(+)T cells and Th17 cells were significantly higher in untreated group than that in healthy control group (P < 0.05), the frequencies of CD3(+)CD8(+)T cells and Treg cells were significantly lower in untreated group than that in healthy control group (P < 0.05), the ratio of Th17/Treg was significantly higher in untreated group than that in healthy control group (P < 0.05). The frequencies of Th17 were not statistically different between remission and healthy control groups, the frequencies of Treg cells were significantly lower in remission group than that in healthy control group (P < 0.05), the ratio of Th17/Treg was significantly higher in remission group than that in healthy control group (P < 0.05), frequencies of Th17 cells were markedly lower in remission group than that in untreated group (P < 0.05). It is concluded that Th17/Treg imbalance exists in patients with CLL, which may play a key role in pathogenesis and development of CLL.

[Early detection of MRD in peripheral blood after induction chemotherapy of newly diagnosed patients with AML and its correlation with curative effects].

The purpose of this study was to detect the minimal residual disease (MRD) in peripheral blood of newly diagnosed patients with acute myeloid leukemia (AML) on day 8 of induction chemotherapy and analyze the correlation between day 8 MRD (D8RD) and therapeutic effectiveness. 29 adult patients (13 males and 16 females, aged 16 - 75 years, median 41 years) with AML diagnosed and treated in West China Hospital from September 2009 to June 2010 were analyzed and followed up in the study. The leukemia-associated aberrant immunophenotype (LAIP) of all the patients were detected by multiparameter flow cytometry (FCM) before therapy. The level of MRD in the peripheral blood at day 8 of induction chemotherapy was detected by FCM based on the LAIP. The overall survival curve was drawn by calculation using Kaplan-Meier method using, and the comparison between different groups was carried out by Log-rank test. The results indicated that after first course therapy, the levels of peripheral D8RD in 7 out of 29 AML cases were lower than 0.01% (negative group), and that in another 22 cases were higher than 0.01% (0.08% - 55%, positive group). The sex, age, WBC, LDH, percentage of bone marrow blasts at diagnosis in these groups were not statistically different. 6 cases achieved CR (86%) in D8RD negative group, and also 6 cases achieved CR (27%) in D8RD positive group, CR rate in D8RD negative group was higher than in D8RD positive group (86% vs 27%, P < 0.05). The median follow-up of 29 cases lasted for 15 months; the 1-year overall survival rate of D8RD negative and D8RD positive groups was 100% and 39.4%, respectively (P < 0.01). It is concluded that MRD level in peripheral blood at day 8 of induction chemotherapy is an early index to predict clinical efficacy of induction therapy in AML.

Individualized leukemia cell-population profiles in common B-cell acute lymphoblastic leukemia patients.

Immunophenotype is critical for diagnosing common B-cell acute lymphoblastic leukemia (common ALL) and detecting minimal residual disease. We developed a protocol to explore the immunophenotypic profiles of common ALL based on the expression levels of the antigens associated with B lymphoid development, including IL-7Rα (CD127), cytoplasmic CD79a (cCD79a), CD19, VpreB (CD179a), and sIgM, which are successive and essential for progression of B cells along their developmental pathway. Analysis of the immunophenotypes of 48 common ALL cases showed that the immunophenotypic patterns were highly heterogeneous, with the leukemic cell population differing from case to case. Through the comprehensive analysis of immunophenotypic patterns, the profiles of patient-specific composite leukemia cell populations could provide detailed information helpful for the diagnosis, therapeutic monitoring, and individualized therapies for common ALL.

Growth-inhibitory and apoptosis-inducing effects of tanshinones on hematological malignancy cells and their structure-activity relationship.

This study has investigated the growth-inhibitory and apoptosis-inducing effects of dihydrotanshinone, tanshinone I, tanshinone IIA, and cryptotanshinone on hematological malignancy cell lines, aiming to explore their structure-activity relationship. The growth-inhibitory effects of the tanshinones on K562 and Raji cells were assessed using a modified MTT assay; the apoptosis-inducing effects were assessed by fluorescence microscopy and flow cytometry analysis. The changes in cellular morphology were observed using an inverted phase-contrast microscope. MTT results revealed that these tanshinones inhibited cell proliferation in a concentration-dependent and time-dependent manner. The IC50 values of dihydrotanshinone, tanshinone I, tanshinone IIA, and cryptotanshinone for K562 cells were 3.50, 13.52, 19.32, and 47.52 µmol/l at 24 h; 1.36, 4.70, 5.67, and 22.72 µmol/l at 48 h; and 1.15, 1.59, 2.82, and 19.53 µmol/l at 72 h, and the values for Raji cells were 3.30, 4.37, 12.92, and 52.36 µmol/l at 24 h; 1.55, 1.71, 6.54, and 25.45 µmol/l at 48 h; and 1.07, 1.38, 1.89, and 18.47 µmol/l at 72 h. The flow cytometry analysis demonstrated that these tanshinones induced apoptosis of K562 cells in a concentration-dependent manner, and dihydrotanshinone as well as tanshinone I were more potent than tanshinone IIA and cryptotanshinone. Some noticeable apoptotic morphologies could be observed by fluorescence microscopy on tanshinones-treated Raji cells. Collectively, these tanshinones caused growth inhibition and apoptosis in hematological malignancy cell lines, with dihydrotanshinone being the most potent, followed by tanshinone I, tanshinone IIA, and cryptotanshinone. These results suggested that the structure of aromatic ring A enhanced the cytotoxicity and the structure of ring C may have contributed to the cytotoxicity, but the mechanisms need to be further investigated.

[Preliminary clinical evaluations of panipenem-betamipron in the treatment of hematological malignancy infections].

OBJECTIVE: To evaluate the clinical efficacy and safety of intravenous panipenem-betamipron in the treatment of hematological malignancies infections. METHODS: From October 2009 to December 2010, a total of 286 hematological malignancy infection patients were recruited into this open-label, perspective and multicenter clinical trial to receive an intravenous daily dose panipenem-betamipron of 0.5 g every 6 or 8 hours for 7 - 14 days. All clinical change and adverse reactions were recorded. RESULTS: The total effective rate of panipenem-betamipron in the treatment of hematological malignancy infections was 86.6% (206/238). The effective rates of septicemia, pulmonary infections, urinary tract infections, digestive canal infections, oral infections and other infections were 68.2% (15/22), 89.3% (100/112), 77.8% (14/18), 100% (22/22), 83.3% (10/12) and 86.5% (45/52) respectively. The overall bacterial eradication rate was 85.07% (57/67) and the rate of adverse reactions 5.9% (17/286). CONCLUSION: Panipenem-betamipron is both safe and effective in the treatment of hematological malignancy infections.

FMS-like tyrosine kinase 3 internal tandem duplication and the patterns of its gene sequence in 207 Chinese patients with de novo acute myeloid leukemia.

CONTEXT: Constitutive activation of the FMS-like tyrosine kinase 3 (FLT3) receptor tyrosine kinase by internal tandem duplication (ITD) has been researched in patients with de novo acute myeloid leukemia (AML). OBJECTIVE: To study the patterns of FLT3-ITD in Chinese patients with AML. DESIGN: A total of 207 patients with de novo AML were enrolled in the study. Genomic DNA was extracted from peripheral blood and polymerase chain reaction was performed. GeneScan was used to analyze the mutant to wild-type ratio. The sequencing of mutated genes was performed to confirm the mutation types and exclude false positives. RESULTS: A total of 42 cases (20.3%) were associated with mutations. FLT3-ITD was found equally in AML subtypes M1 to M6. The level of the ITD allele was heterogeneous. GeneScan showed that the mutant to wild-type ratio ranged from 0.03 to 3.78 (median, 0.43). Patients with a high ratio had significantly lower cancer remission rates and shorter survival. They also showed distinct clinical features including higher white blood cell counts and higher CD7 and CD56 expression. The length of the duplicated fragment was 26 to 57 bp (median, 43 bp). Twenty-two cases (52%) had simple tandem duplications, while 20 other cases (48%) had an extra interval of 12 to 30 bp before the tandem duplications. A hexanucleotide consisting of GAAAAG was found exclusively in the intervals. Patients with this GAAAAG interval showed better survival. The ITD to wild-type ratio, gene pattern, and CD7 expression status appear to be independent prognostic indices for patients with AML. CONCLUSION: Detection of FLT3 mutation is fast, easy, and inexpensive. The mutant to wild-type ratio is helpful for performing detailed risk stratification. DNA sequence analysis is more precise for confirming and evaluating the mutation pattern.

[Influence of immunosuppressive therapy on expression of TNF-α/IFN-γ in cytoplasm of peripheral blood lymphocytes of patients with aplastic anemia].

The purpose of this study was to investigate the influence of immunosuppressive therapy on the expression of TNF-α/IFN-γ in cytoplasm of peripheral blood lymphocytes of patients with aplastic anemia (AA). The expression of TNF-α and IFN-γ in cytoplasm of peripheral CD3(+) lymphocytes were measured by flow cytometry in 25 cases of de novo AA patients and 20 cases of AA after immunosuppressive therapy. The results showed that the positive rates of CD3(+)/TNF-α(+) and CD3(+)/IFN-γ(+) in de novo AA patients were (5.97 ± 6.78)% and (15.20 ± 11.28)% respectively, and (1.56 ± 0.87)% and (1.76 ± 0.87)% in normal controls respectively. There was significant difference between de novo AA patients and normal controls (p < 0.05). The positive rates of CD3(+)/TNF-α(+) and CD3(+)/IFN-γ(+) in immunosuppressive therapy group were (1.67 ± 1.26)% and (4.35 ± 4.33)% respectively. The difference between immunosuppressive therapy group and de novo AA group was statistically significant (p < 0.05). It is concluded that the levels of intracellular TNF-α and IFN-γ in AA patients are higher than those in normal controls. Immunosuppressive therapy significantly reduces the expression of intracellular TNF-α and IFN-γ. Its relationship with the clinical treatment is worth further observing.

[Immunophenotype characteristics and prognosis of acute leukemia patients with cross expressing lymphoid and myeloid lineage associated antigens].

The aim of study was to investigate the immunophenotype characteristics and prognosis of acute leukemia patients with cross-expressing lymphoid and myeloid lineage-associated antigens. The immunophenotypes of leukemic cells were examined by using flow cytometry. All patients were classified into several groups according to FAB subtypes and immunophenotyping. The cross-expressed antigens analyzed for AML included CD2, CD7, CD19, CD56 and other co-expressed lymphoid antigens. The myeloid antigens analyzed for ALL included CD13 and co-expressed CD13/CD33. ALL and AML patients without expression of cross-expressing antigens were selected as control. Complete remission (CR) ratio and relapse-free survival (RFS) of patients in all groups were compared. The results indicated that among 161 patients analyzed, 91 cases of AML with cross-expressing lymphoid and myeloid antigens included that 24 cases of AML expressed lymphoid surface marker-CD7, namely CD7(+) AML, 14 cases of AML only expressed lymphoid surface marker-CD19, namely CD19(+) AML, 8 cases of AML expressed lymphoid surface marker-CD2 (including CD2/CD19 co-expressed), namely CD2(+) AML, 10 cases of AML expressed lymphoid surface marker-CD56 (including CD56/CD19 or CD56/CD2 co-expressed), namely CD56(+) AML, 16 cases of AML expressed two or more lymphoid surface markers, namely Ly ≥ 2(+) AML, 9 cases of ALL expressed myeloid surface markers CD13, namely CD13(+) ALL, 10 cases of ALL expressed myeloid surface markers CD13 and CD33, namely CD13/CD33(+) ALL. 29 cases of ALL did not expressed myeloid surface markers, namely My(-) ALL, and 41 case of AML did not expressed lymphoid surface markers, namely Ly(-) AML. CR ratio and RFS of Ly ≥ 2(+) AML patients were lower than those of Ly(-) AML patients. RFS of CD56(+) AML patients was lower, but CR ratio had no significant difference, when compared with Ly(-) AML patients. CR ratio and RFS of other AML patients with cross-expressing antigens had no significant difference when compared with Ly(-) AML patients. CR ratio and RFS of CD13(+) ALL and CD13/CD33(+) ALL patients had no significant difference when compared with My(-) ALL patients. It is concluded that the importance of cross-expressing antigens for prognosis of patients should be analyzed concretely. CD56(+) AML and Ly ≥ 2(+) AML have bad prognosis, while other cross-expressed lymphoid and myeloid lineage-associated antigens have no impact on prognosis of acute leukemia patients.

[Flow cytometric analysis of cerebrospinal fluid in the diagnosis of central nervous system leukemia].

OBJECTIVE: To evaluate the value of flow cytometric immunophenotyping of cerebrospinal fluid (CSF) cells in the diagnosis of central nervous system leukemia. METHODS: Ninety two CSF samples were analyzed with 4-color flow cytometry. Antibody panles CD19/CD34/CD3/CD45, CD117/CD34/CD5/CD45, CD7/CD34/ CD19/CD45, CD7/CD3/HLA-DR/CD45, CD20/CD10/CD3/CD45, and anti-g/anti-lambda/CD19/CD45 were used in determining cell composition and detecting abnormal cells. The results of flow cytometry were compared with conventional cell count and morphology. Flow cytometry analysis was repeated for five samples 48 hours after the initial test. RESULTS: Abnormal cells were found in 33 out of the 92 (35.9%) samples. Among the 59 samples taken from patients with lymphocyte neoplasm, CD19 + blast cells were found in the CSF in 13 patients with B-cell lymphoblastic leukemia; CD7+ blast cells were found in 4 T-ALL cases; and monoclonal CD19+ cells were found in 6 other types of lymphoma cases. In the 32 patients with clinically diagnosed myeloid leukemia, CD117+ myeloid cells were found in the CSF of 7 patients and B cell blast cells were found in 2 CML cases. The abnormal cells in the CSF detected by immunophenotyping decreased significantly 48 hours after the initial test. Abnormal cells were detected in 25 samples (27.2%) by morphology, less than those detected by immunophenotyping. The cell concentrations of the eight samples in which abnormal cells were only detected by flow cytometry were lower than 10 X 10(6)/L. The immunophenotyping results of two ALL patients were still positive when morphologic results had become negative after chemotherapy. CONCLUSION: Flow cytometric analysis of CSF may be helpful in the diagnosis of meningeal leukemia. It has higher positive rate and better accuracy than cytomorphology and cell count.