Analysis of prognostic factors of extranodal NK/T-cell lymphoma treated with pegaspargase/L-asparaginase: a multicenter retrospective study / 中华血液学杂志

Objective: To explore the prognostic factors of extracellular NK/T cell lymphoma (ENKTL) treated with pegaspargase/L-asparaginase. Methods: The clinical data of 656 ENKTL patients diagnosed at 11 medical centers in the Huaihai Lymphoma Working Group from March 2014 to April 2021 were retrospectively analyzed. The patients were randomly divided into two groups: a training set (460 cases) and a validation set (196 cases) at 7∶3, and the prognostic factors of the patients were analyzed. A prognostic scoring system was established, and the predictive performance of different models was compared. Results: Patients' median age was 46 (34, 57) years, with 456 males (69.5% ) and 561 nasal involvement (85.5% ). 203 patients (30.9% ) received a chemotherapy regimen based on L-asparaginase combined with anthracyclines, and the 5-year overall survival rate of patients treated with P-GEMOX regimen (pegaspargase+gemcitabine+oxaliplatin) was better than those treated with SMILE regimen (methotrexate+dexamethasone+cyclophosphamide+L-asparaginase+etoposide) (85.9% vs 63.8% ; P=0.004). The results of multivariate analysis showed that gender, CA stage, the Eastern Cooperative Oncology Group performance status (ECOG PS) score, HGB, and EB virus DNA were independent influencing factors for the prognosis of ENKTL patients (P<0.05). In this study, the predictive performance of the prognostic factors is superior to the international prognostic index, Korean prognostic index, and prognostic index of natural killer lymphoma. Conclusion: Gender, CA stage, ECOG PS score, HGB, and EB virus DNA are prognostic factors for ENKTL patients treated with pegaspargase/L-asparaginase.

Use of fish oil lipid emulsion in patients undergoing major surgery and those with systemic inflammatory response syndrome: a cost-effectiveness analysis / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To investigate the cost-effectiveness of fish oil in patients undergoing major surgery and those with systemic inflammatory response syndrome(SIRS).</p><p><b>METHODS</b>A retrospective study was conducted in patients undergoing major surgery and those with SIRS on admission in the Zhongshan Hospital from January 2008 to December 2011. Fish oil group was enrolled and matched to control group by 1:2 for gender, age, diagnosis, and surgical procedure. There were 220 pairs of patients who were not admitted to ICU, 102 pairs of patients admitted to ICU, and 66 pairs of patients with SIRS. The clinical outcomes and costs were measured and cost-effectiveness analyses were conducted.</p><p><b>RESULTS</b>The clinical outcomes and costs showed no significant difference between the fish oil group and the control group in those patients who were not admitted to ICU(P>0.05). Fish oil fat emulsion supplementation significantly reduced the length of total hospital stay, postoperative hospital stay, ICU stay, re-operation rate, infection rates, perioperative mortality in patients admitted to ICU and those with SIRS(P<0.05). The cost-effectiveness ratio of non-reoperation rate, non-infection rate, and survival rate were lower in those patients receiving fish oil fat emulsion as compared with those without fish oil administration. Fish oil fat emulsion supplementation could reduce cost-effectiveness ratios of non-reoperation rate, non-infection rate and survival rate by 105 RMB, 160 RMB, and 89 RMB respectively in major surgical patients who admitted to ICU, and by 670 RMB, 280 RMB, and 220 RMB respectively in SIRS patients.</p><p><b>CONCLUSIONS</b>Addition of fish oil fat emulsion to clinical nutrition may have positive effects on critically ill patients. It seems that the effects of fish oil fat are strongly related to the severity of patient's underlying disease. Fish oil fat emulsion supplementation shows acceptable cost-effectiveness ratio and pharmacoeconomic value.</p>

Relations between saliva arsenic levels and serum arsenic and urinary arsenic of rats after exposed to different levels of sodium arsenite / 中国地方病学杂志

Objective To investigate the relations between saliva arsenic levels and serum arsenic and urinary arsenic of rats after exposed to different levels of sodium arsenite.Methods Thirty-two SD rats were randomly divided into four groups(8 rats in each group),namely the control group,the low,the medium,and the high doses of sodium arsenite exposure groups.Rats of the control group were given 0.9％ NaCI by gavage,and other three groups were given sodium arsenite of 0.2,2.0,20.0 mg/kg body weight by gavage.All animals were administrated every other day for two weeks,then saliva,blood,urine and tissue organs were collected,organ coefficients were calculated,total arsenic concentrations in blood and urine were detected by Atomic Fluorescence Spectrometry(AFS-230) and total arsenic concentration in saliva was detected by Inductively Coupled Plasma Mass Spectrometer(ICP-MS).Results The weight gain values of rats exposed to sodium arsenite were lower than that of the control group,the difference was statistically significant between the highest dose group[(76.13 ± 17.19)g]and the control group[(103.00 ± 12.31)g,P ＜ 0.05].The liver and kidney organ coefficients in the highest dose group [(3.92 ± 0.54)％,(0.96 ± 0.15)％]were significantly higher than that in the control group[(3.27 ± 0.35)％,(0.76 ± 0.05)％,P ＜ 0.05 or ＜ 0.01].The total arsenic concentrations in saliva[(0.044 ± 0.019),(0.211 ± 0.071),(1.128 ± 0.380)mg/L],blood[(11.832 ± 1.887),(45.032 ± 7.216),(121.839 ± 17.323)mg/L]and urine[(0.138 ± 0.085),(0.874 ± 0.328),(8.843 ± 1.754)mg/L]in the three treatment groups were significantly higher compared with that of the control group [(0.018 ± 0.014),(2.267 ± 0.370),(0.025 ± 0.011)mg/L,all P ＜ 0.05],furthermore,there was a significant difference among the three treatment groups (all P ＜ 0.05).The arsenic contents in saliva were significantly correlated with blood arsenic and urinary arsenic,the correlation coefficient was 0.934 and 0.960,respectively (all P ＜ 0.01).Conclusions High dose of arsenic exposure,with a strong toxicity to liver and kidney,can inhibit the increase of rat body weight.Arsenic dose-response relationship exists in the saliva,and saliva arsenic is significantly correlated with blood arsenic and urinary arsenic,suggesting that salivary arsenic can be used as a new biomarker for assessing human exposure to arsenic.

The research of combining high resolution melting with multiplex ligation-dependent probe amplification technology in the mutation scanning for PAH gene / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To explore the value of combining high resolution melting (HRM) with multiplex ligation-dependent probe amplification (MLPA) for detecting mutations underlying phenylketonuria.</p><p><b>METHODS</b>HRM was used for detecting small mutations in phenylalanine hydroxylase gene (PAH) of 26 phenylketonuria patients. The results were verified with DNA sequencing. MLPA was used for detecting potential deletions/duplications in the PAH gene. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis was performed for additional potential mutations.</p><p><b>RESULTS</b>A total of 21 mutations were found in 44/52 alleles (84.62%), which included a dupEx4. Among the 21 types of mutation, 19 were reported previously, and the remaining two were novel mutations: c.584_585insA and IVS10+1G>T. In addition, the mutation of R243Q (25%) was the most common type in China.</p><p><b>CONCLUSION</b>The study showed that the combination of HRM and MLPA could increase the detection rate for mutation in PKU. The study has added new information to the human mutation database of PAH and provided a basis for clinical diagnosis and prenatal counseling.</p>

Monitoring of plasma concentration of imatinib mesylate in patients with chronic myeloid leukemia / 中华血液学杂志

<p><b>OBJECTIVE</b>To analyze the clinical efficacy of imatinib mesylate (IM) for Ph-positive or BCR-ABL positive chronic myeloid leukemia (CML) to couple the trough plasma concentrations (C mins) of IM with clinical responses and adverse events (AEs).</p><p><b>METHODS</b>One hundred and one CML patients received IM therapy, and Cmins of IM were determined in 30 patients.</p><p><b>RESULTS</b>(1) Cumulative complete hematological response (CHR), major cytogenetic response (MCyR), complete cytogenetic response (CCyR) and negative BCR/ABL fusion gene rates were 96.6%, 86.5%, 77.5% and 47.2%, respectively, in CML-CP patients. In accelerated and blastic phases (AP and BC) patients, CHR, MCyR, CCyR and negative BCR-ABL fusion gene rates were 58.3%, 25.0%, 25.0%, 8.3%, respectively. (2) Mean Cmins of IM was significantly higher in the CCyR at 1 year [(1472 +/- 482) microg/L] group than in the non-CCyR at 1 years group [(1067 +/- 373) microg/L] (P < 0.05), and higher in the MMR at 1 year group than in the non-MMR at 1 years group [(1624 +/- 468) microg/L vs (1137 +/- 404) microg/L, P < 0.05].</p><p><b>CONCLUSION</b>IM significantly improves cytogenetic and molecular response, event-free survival, and overall survival for patients with Ph-positive CML. The Cmins of IM exerts a significant impact on clinical response (CCyR and MMR at 1 year).</p>

Biomarkers of early vascular endothelial injury with low-arsenic exposure in drinking water / 中国地方病学杂志

Objective To observes the change of early effective biomarkers of endothelial injury with lowarsenic exposure in drinking water. MethodsNinety rurad residents, who had lived in Yanhe village, Xuyi county and Jiangsu province for at least 10 years, were recruited by simple random sampling in this study. The level of arsenic in their household shallow well were divided into three groups, which were ＜ 10 (32 people), 10 - 50(28 people) and ＞ 50 μg/L(30 people). Blood samples from individuals were collected. Malondialdehyde(MDA) in human plasma, which is considered as the most important marker for monitoring lipid peroxidation, was determined as conjugate with tetrabutylammonium hydrogen sulphate(TBA). The level of anti-superoxide anion radical(O-·2),C-reactive protein(CRP) and NO in human plasma was measured with colorimetry, turbidimetry and nitric acid reductase, respectively. The number of circulating endothelial progenitor cells(CEPCs) in peripheral blood was analyzed by CD133+/KDR+ antibodies and flow cytometry. Results Ninety cases underwent questionnaires. Between the groups, the difference of the levels of MDA (61.1, 65.5, 67.5 μmol/kg), O-·2 (4774.6, 5143.3, 4736.0 U/kg) ,CRP[(5.92 ± 2.44), (5.11 ± 2.40), (5.55 ± 2.96)mg/L], and NO[(659.8 ± 387.5), (667.4 ± 486.6), (762.1 ±763.2)μmol/kg], was not statistically significant (F =0.00, 0.46, 0.80, 0.47, all P ＞ 0.05). The difference of the number of CEPCs in different groups of arsenic in drinking water was statistically significant(0.96 x 10-5, 0.77 x 10-5,1.59 x 10-5, F=5.08, P＜ 0.05), where ＜ 10, 10 - 50 μg/L groups were significantly lower than ＞ 50 μg/L group (q =4.58, 6.65, all P ＜ 0.05). ConclusionsThe number of CEPCs in peripheral blood changes significantly with lower-arsenic exposure, whereas there are no obvious changes with the markers of oxidized damage and inflammation. This is the first human demonstration showing that lower-arsenic exposure may cause endothelial injury.

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>

Study of fibrinolysis inhibitors in 117 acute leukemia patients / 中华血液学杂志

<p><b>OBJECTIVE</b>To explore the clinical significance of fibrinolysis inhibitors including thrombin activatable fibrinolysis inhibitor(TAFI), plasminogen activator inhibitor (PAI) and alpha2-plasmin inhibitor (alpha2-PI) in acute leukemia (AL).</p><p><b>METHODS</b>PAI-1 antigen and TAFI antigen were investigated by enzyme-linked immunosorbent assay and PAI activity, alpha2-PI activity, TAFI activity by chromatography substrate assay in 117 AL patients and 50 normal controls.</p><p><b>RESULTS</b>1) alpha2-PI activities in AL patients were reduced, especially in ALL patients [(96.8 +/- 21.2)%]; 2) PAI-1 antigens in AML patients [(37.8 +/- 9.2) microg/L] were significantly higher than that in normal controls [(33.8 +/- 4.9) microg/L]; 3) PAI-1 antigens in APL [(37.8 +/- 9.0) microg/L] and AML-M5 patients [(39.9 +/- 11.6) microg/L] were higher and TAFI activities in APL patients [(13.3 +/- 4.8) mg/L] were lower than that in normal controls [(16.9 +/- 2.6) mg/L]; 4) PAI-1 antigens of relapsed/refractory patients (39.6 +/- 11.6) microg/L) were significantly elevated; 5) TAFI activities in bleeding patients [(13.2 +/- 5.3) mg/L] were significantly lower than that in normal control as well as non-bleeding patients (17.0 +/- 4.6) mg/L); 6) The severity of bleeding was negatively correlated with TAFI activity (r = - 0.276, P <0.05).</p><p><b>CONCLUSIONS</b>Hyperfibrinolysis caused partially by decrease of alpha2-PI and TAFI activity takes part in the pathogenesis of bleeding in AL.</p>

Notch signaling in human breast cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To explore the role of Notch signaling in human breast cancers, the expression of Notch1 and its ligand JAG1 in human breast cancers and their relationships with clinical stages of breast cancers were analyzed.</p><p><b>METHODS</b>RT-PCR was used to detect the expression of Notch1 and JAG1 in 62 breast cancer specimens and 22 normal breast tissues at the margin of tumor sections, and the statistical difference of expression rates and standardized coefficient between the two groups were analyzed. To compare the expression intensity of Notch1 and JAG1 at different development stages of the illness and at different stages with or without axillary node metastasis.</p><p><b>RESULTS</b>The expression rate and standardized coefficient of Notch1 in human breast cancers were significantly higher than those of normal breast tissues at the margin of tumor sections. The expression rate of JAG1 in human breast cancers was 15%, while JAG1 was not detected in normal breast tissues at the margin of tumor sections. The standardized coefficient of Notch1 in cases with axillary node metastasis was significantly higher than that in cases without axillary node metastasis. The standardized coefficient of Notch1 at stage I was significantly lower than that at stage II, and stage II was significantly higher than stage III. There was no statistically significant difference between stage I and stage III.</p><p><b>CONCLUSION</b>Notch1 and JAG1 are highly expressed in human breast cancers, indicating that the aberrant expression and activation of Notch1 may be related with tumorigenesis of human breast cancer. Notch1 may play different roles at different developmentl stages of human breast cancer.</p>

Reversal of multi-drug resistance in K562/A02 cells by two short hairpin RNAs (shRNA) of mdr1 / 中华血液学杂志

<p><b>OBJECTIVE</b>To construct two recombinant plasmids of mdr1 and mcl1 shRNA, and to investigate their reversal effect on drug resistance in K562 adriamycin resistant cell lines (K562/A02).</p><p><b>METHODS</b>Two oligonucleotides of mdr1 and mcl1 gene were designed referring to that of GenBank, double-stranded DNA was derived through annealing, and cloned into pRNAT vector digested by two restricted endoenzymes. K562/A02 cells were transfected with the recombinant plasmids. The mdr1 mRNA expression and its protein product P-glycoprotein (P-gp) were detected by RT-PCR and flow cytometry. The expression of mcl1 gene was detected by RT-PCR. 50% inhibition concentration (IC50) of adriamycin (ADM) on K562/A02 cells was determined by MTT method. Cells apoptosis was analyzed by flow cytometry.</p><p><b>RESULTS</b>Comparing with K562/A02 cells, the shRNA of mdrl or mcl1 gene in vitro can remarkably increase the sensitivity of K562/A02 to adriamycin, down-regulate mdr1 or mcl1 gene expression, increase the K562/A02 cells apoptosis rates induced by adriamycin. Cotransfection of mdrl and mcl1 genes shRNA can also down-regulate the expression of their gene, more remarkably increase the sensitivity and apoptosis of K562/ A02 to adriamycin.</p><p><b>CONCLUSION</b>Transfection of mdrl or mcl1 gene shRNA can promote the sensitivity of K562/A02 to adriamycin and cotransfection of the two shRNA can more remarkably do so. The mel1 gene might be involved in adriamycin resistant in K562/A02 cells.</p>

Function of Delta4 gene and its effects on 32D cell differentiation / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Notch activation leads to transcriptional suppression of lineage-specific genes, inhibiting differentiation in response to inductive signals. The Notch signal system contains three parts: Notch molecules, Notch ligands and effectors. Delta4 is a newly-discovered Notch ligand which has received the attention of few detailed studies. This study sought to explore the biological function of Delta4 and observe its effects on 32D cell differentiation.</p><p><b>METHODS</b>Delta4-expressing vector pTracer.CMV.Delta4.FLAG was constructed using molecular biological techniques. CHO cells stably transfected with pTracer.CMV.Delta4.FLAG were confirmed to have a Delta4 protein band via Western blotting. High-expression Delta4-CHO clones were selected for the following functional studies. Notch1-CHO and Notch2-CHO were used as host cells. After transiently transfecting with transition protein 1 (TP1), Delta4 activity was compared in both cell lines by means of luciferase analysis. CHO cells were incubated with Notch1-32D cells that had been transfected with Notch1 and were observed for granulocyte colony-stimulating factor (G-CSF)-induced differentiation. Jagged2-CHO and Delta4-CHO cells transfected with the Notch ligands Jagged2 and Delta4, respectively, were incubated with Notch1-32D cells to observed inhibition of Notch on G-CSF-induced differentiation.</p><p><b>RESULTS</b>The vector pTracer.CMV.Delta4.FLAG was constructed successfully. CHO cells were stably transfected with the vector pTracer.CMV.Delta4.FLAG. Two CHO cell lines expressing Delta4 at high levels were selected for use in the study. Delta4 was found to induce signal activity via both Notch1 and Notch2 and the induction of signaling activity was stronger in Notch2 cells than in Notch1 cells. Compared with other Notch ligands, Delta4 was slightly weaker than Jagged2, but stronger than Delta1 and Jagged1 in terms of Notch1 ligands. In terms of Notch2, Delta4 had a strong signaling activity, but was weaker than Delta1, Jagged1, and Jagged2. Jagged2 could inhibit Notch1-32D cell differentiation induced by G-CSF, but Delta4 could not.</p><p><b>CONCLUSIONS</b>Delta4 induces both Notch1 and Notch2 activity and is a ligand for both of them. The effect of Delta4 is stronger on Notch2 than that on Notch1. Jagged2 can inhibit Notch1-32D cell differentiation induced by G-CSF, but Delta4 cannot.</p>