1.Pegasparaginase as ifrst-line treatment of children with leukemia and lymphoma
Hongsheng WANG ; Xiaowen ZHAI ; Fengjuan LU ; Jun LI ; Hui MIAO ; Xiaowen QIAN ; Xiaohua ZHU ; Yue WU
China Oncology 2014;(5):374-380
Background and purpose: L-asparaginase (L-Asp) is an important drug in the treatment of childhood lymphoid neoplasms at present, but a lot of adverse reactions of L-Asp were observed. Pegasparaginase (PEG-Asp) is available in China in recent years. This study aimed to explore efifcacy and side-effect of PEG-Asp as ifrst-line treatment in childhood acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma (LBL). Methods:A total number of 211 ALL or LBL patients were treated with CCLG 2008 or BFM-90 protocol with PEG-Asp or L-Asp between Apr. 2008 and Mar. 2013;42 patients, among whom, were 35 ALL patients and 7 LBL patients, were treated with PEG-Asp as ifrst-line treatment;169 patients were treated with L-Asp as ifrst-line treatment (including 53 patients treated with L-Asp during induction protocol; with PEG-Asp during consolidate protocol). The clinical outcome and adverse reaction of PEG-Asp with L-Asp were observe and compared. Results: There were 35 ALL patients in PEG-Asp ifrst-line treatment group and the complete remission rate after 1 course of PEG-Asp was 97.1%,however, which was 83.3%of high risk ALL patients. The complete remission rate of 7 LBL patients of PEG-Asp ifrst-line treatment group was 57.1%. There was no signiifcant difference between 2 groups (P>0.05). Thirty-four patients relapsed including 5 patients of PEG-Asp ifrst-line treatment group, 16 patients of L-Asp ifrst-line treatment group and 13 patients treated with L-Asp during induction protocol and with PEG-Asp during consolidate protocol. Thirty-one patients died including 3, 18, 10 patients in 3 groups respectively. Twenty-two patients died of relapse, 4 died without remission, 5 died of complications. There was also no signiifcant difference between 2 groups (P>0.05). The incidence rates of adverse reactions were 47.6% and 63.3% respectively. Anaphylaxis, liver functions abnormalities, blood coagulation abnormalities, gastrointestinal reaction, hyperglycemia and pancreatitis were common in our patients. The incidence rate of anaphylaxis in PEG-Asp as ifrst-line treatment group was lower than other groups (P=0.03). But there was no signiifcant difference been observed in the incidence of other adverse reaction. Conclusion: The short-term efifcacy of PEG-Asp as the ifrst-line treatment in childhood leukemia and lymphoma was satisfactory and the incidence rate of anaphylaxis was lower. However, we will still pay much attention to adverse reaction monitoring of PEG-Asp.
3.The establishment and application of double TaqMan real-time fluorescence nested PCR method for rapid detection of α-thalassemia SEA deletion
Xiaowen YUAN ; Yunke LIU ; Qian HUANG ; Wanjun ZHOU
Chinese Journal of Laboratory Medicine 2011;34(8):681-685
Objective To establish a double TaqMan real-time fluorescence nested PCR method for rapid detection of α-thalassemia SEA deletion.Methods One hundred blood samples for thalassemia screening were collected from May to July of 2010 in the Tianhe Maternal and Child Health Hospital of Guangzhou.Seven fetal specimens for prenatal diagnosis were collected from December 2010 to February 2011 in Dongguan TungWah Hospital(2 villi and 5 amniotic fluid specimens).Fifty samples of α-thalassemia SEA deletion with genotyping results were selected from the sample bank of our laboratory.The double TaqMan real-time fluorescence nested PCR was applied to detect the truncated sequence of SEA deletion and the normal sequence within deletion range simultaneously for all these samples with the same detecting system.The genotype of α-thalassemia SEA deletion was accurately acquired according to the positive result of fluorescent PCR combined with the Ct value difference.Meanwhile,the accuracy and feasibility of this method were verified and analyzed by parallely detecting these samples with routine gapPCR for α-thalassemia SEA deletion.The genotype could be obtained according to PCR amplification and agarose gel electrophoresis.Results Two amplification efficiencies of the optimized dual TaqMan real-time fluorescence nested PCR system established in this study were both close to 100% with the slops of -3.153 and -3.182,respectively.The results of 50 samples of α-thalassemia SEA deletion with genotyping results showed that this method could not only realize rapid diagnosis,but also effectively avoid false negative or false-positive misdiagnosis by accurately determine the external contamination in the sample.Among 100 blood samples,eleven samples with SEA deletion were detected respectively and the diagnosis coincidence rate of these two methods was 100%,3 samples with SEA deletion were detected by gap-PCR,but 2 samples with SEA deletion and 1 villi sample with normal genotype but contaminated by SEA were detected by this method among 7 fetal samples.Conclusions A double TaqMan real-time fluorescence nested PCR method for α-thalassemia SEA deletion was developed.The method is a rapid and reliable test with simple operation,and is suitable for large-scale population screening and routine molecular diagnosis.
4.Significance of triggering receptor expressed on myeloid cells-1 of cord blood leukocytes in neonates
Xiaowen WENG ; Lei QIAN ; Qiangsheng LYU ; Changhong SUN ; Hui ZHOU
Chinese Journal of Perinatal Medicine 2015;(7):533-537
Objective To investigate the triggering receptor expressed on myeloid cells-1(TREM-1) of cord blood leukocytes in neonates and the transcription level of mRNA, and analyze its promoting function of inflammatory cytokine secretion. Methods During the period from September 2013 to March 2014, cord blood was collected from 20 term neonates at the time of birth, and peripheral blood was collected from 20 healthy adults. The expression of TREM-1 and TREM-1 mRNA on leukocytes was observed using flow cytometry and real-time reverse transeription-polymerase chain reaction, respectively. After the whole cord blood was stimulated by lipopolysaccharide (LPS) or LP17 plus LPS, the contents of interleukin (IL)-6, tumor necrosis factor-α (TNF-α), IL-8 and soluble TREM-1 (sTREM-1) in the supernatant were analyzed by enzyme linked immunosorbent assay. The statistical significance was determined using the one-way ANOVA test, t test, q test and Pearson correlation coefficient. Results The mean fluorescence intensity of TREM-1 on leukocytes of newborns was not different compared with healthy adults (P>0.05), while the percentage of TREM-1 positive on polymorphonuclear cells was lower than that of healthy adults [(82.3±7.1)% vs (98.6±4.8)%, P<0.05]. The level of TREM-1 mRNA in newborns was lower than in healthy adults (1.16±0.13 vs 1.63±0.24, t=7.714, P<0.01). The LPS treatment significantly increased sTREM-1 in newborn whole blood compared with the control treatment [(156.7±36.3) vs (34.6±6.1) pg/ml, t=13.623, P<0.01]. The concentration of IL-6, TNF-αand IL-8 decreased significantly when TREM-1 was blocked by LP17. In addition, the concentration of sTREM-1 showed a positive correlation with the levels of TNF-α(r=0.519, P<0.05), IL-6 (r=0.507, P<0.05) and IL-8 (r=0.538, P<0.05). Conclusions Healthy newborns exhibit expression of TREM-1 on monocytes similar to healthy adults, and most PMNs express TREM-1 at the newborn stage. Blocking the TREM-1 signal transduction pathway may reduce inflammatory responses of neonate leukocytes.
5.Congenital factorⅦdeficiency:a report of two cases and literature review
Qian ZHAI ; Yun CAO ; Xiaowen ZHAI ; Rong ZHANG
Journal of Clinical Pediatrics 2014;(5):430-433
Objective To study the pathogenesis, clinical characteristics, laboratory tests, treatments and prognosis of con-genital factorⅦdeficiency. Methods The clinical data of two cases of congenital factorⅦdeficiency diagnosed at the Chil-dren’s Hospital of Fudan University and 9 cases reported in the past 10 years retrieved from Pubmed, Web of Knowledge and CNKI, Wangfang database by using the factorⅦdeficiency , congenital, newborn and case report as keyword were reviewed and analyzed. Results All cases were full term birth with normal birth weight (>2 500 g), including 4 females and 7 males. Pa-rental consanguinity was found in 3 cases, and a family history was found in 3 cases. The laboratory tests were characterized by significantly prolonged prothrombin time, normal partial thromboplastin time, and decreased coagulation factorⅦactivity. The coagulation factorⅦactivity of 10 cases were less than 5%. Five cases (45.5%) were treated with human recombinant activated factorⅦ. Four cases (36.4%) treated with plasma or human recombinant activated factorⅦare currently in normal growth and development. Four cases (36.4%) died during the hospitalization. Conclusions A diagnosis of congenital factorⅦdeficiency should be considered in the neonates with severe bleeding, prolonged prothrombin time, normal partial thromboplastin time, and being intractable to vitamin K treatment. Human recombinant activated factorⅦis the first choice of the treatment of congenital factorⅦdeficiency. The further study of gene mutation type will be of great significance for disease screening, diagnosis, treat-ment and prognosis prediction.
6.Efficacy and prognostic risk factors of childhood relapsed acute lymphoblastic leukemia:analysis from a single center
Ping WANG ; Xiaowen ZHAI ; Hongsheng WANG ; Cuiqing FAN ; Xiaowen QIAN ; Hui MIAO ; Yi YU ; Xiaohua ZHU ; Jun LI ; Fengjuan LU
Journal of Leukemia & Lymphoma 2016;25(2):99-105
Objective To investigate the efficacy and prognostic risk factors of ALL-R-2003 protocol in the treatment of relapsed childhood relapsed acute lymphoblastic leukemia (ALL) in single center. Methods A retrospective study of clinical data of 51 children with relapsed ALL from January 2004 to December 2014 was performed by using SPSS version 19.0 statistical software for statistical analysis. Results The median age at initial diagnosis of 51 patients was 5.5 years (range, 0.8-13.4 years). The median time from initial diagnosis to relapse was 25 months (range, 3-68 months) and follow-up time was 39 months (range, 3-116 months). The relapse rate in the standard-risk, intermediate-risk and the high-risk groups were 27.5 % (14/51), 29.4 %(15/51) and 43.1 % (22/51), respectively. The probability of 3-year overall survival (pOS) after relapse was (18.8±5.9)%and the probability of event free survival (pEFS) was (16.2±5.8)%. The 3-year pOS in very early relapse, early relapse and late relapse were 0, (11.7 ±7.7) % and (51.7 ±14.8) %, respectively (P= 0.000). There was no statistical difference in survival rate of different immunophenotype groups and sites of relapse (P> 0.05). The 3-year pOS of group S1, S2, S3, S4 were (50.0±35.4) %, (39.9±1.3) %, (10.0±9.5) % and 0, respectively (P=0.000). The 3-year pOS of bcr-abl and MLL gene positive groups were (25.0±21.7) %and 0, respectively, with no statistically significance compared with the negtive group [(24.1±12.0)%] (P>0.05). The 3-year pOS rates of children with bone marrow transplantation and without transplantation were (40.0 ±15.5) %and (13.0 ±5.9) % respectively (P= 0.038). Conclusions The children who in high risk group at initial diagnose are easily to meet earlier relapse and poorer prognosis. The survival period after relapse of bcr-abl or MLL gene positive cases is very short. Bone marrow transplantation can improve survival rate. Risk group at initial diagnose, relapse time and transplantation are the main factors influencing prognosis, and the relapse time and transplantation are the independent prognostic factors for relapsed childhood ALL.
7.Change in expression of WNK1 in spinal cord of a rat model with bone cancer pain
Mengwei SHEN ; Xiaobo QIAN ; Jianling GAO ; Lina WANG ; Xiaowen MENG ; Jianping YANG
Chinese Pharmacological Bulletin 2016;32(10):1442-1445
Aim To investigate the changes in the ex-pression of WNK1 in spinal cord of a rat model with bone cancer pain. Methods Female SD rats, weig-hing 170 ~200 g, were randomly divided into three groups:normal control group (group C, n=3), sham operation group ( group S, n =3 ) and bone cancer pain group ( group BCP, n =24 ) . Group C was not given any treatment, and group S was injected into the bone marrow of left tibia with 5 μl PBS solution while group BCP with 5 μl WALKER 256 mammary gland cancer cell suspension (approximately 1 × 105 cells). Mechanical paw withdrawal threshold ( MWT ) was measured at d1 before inoculation ( baseline) and d3, 6,9,10,11,12 after inoculation. Group S and C were sacrificed at d 12 while group BCP at d 3 ,6 ,9 ,12 after inoculation and spinal cord ( L4~6 ) were removed at different time points for detection of WNK1 mRNA ex-pression by qRT-PCR and WNK1 protein expression by Western blot. Results Compared with group C and S,group BCP’ s MWT started to decrease since d 3 ( P<0. 05 ) . The mRNA expression of WNK1 in spinal cord was up-regulated(P<0. 05) from d 3 showing an increasing trend over time until d 9 ( peak ) and then down-regulated to d 12 ( P >0. 05 ) while the protein expression upregulated since d6 and also showed an in-creasing trend to d 12 ( P<0. 01 ) . Conclusion The expression of WNK1 in spinal cord of a rat model with bone cancer pain increased abnormally, which may be involved in the occurrence and maintenance of a rat model with bone cancer pain.
8.Clinical symptoms and serum brain-derived neurotrophic factor level between depressive patients with and without attempted suicide behavior
Yongliang LYU ; Zhenxiang ZHOU ; Hongliang ZHU ; Zhiping QIAN ; Rongsheng ZHANG ; Xiaowen XU ; Xiongwei ZHU
Chinese Journal of Primary Medicine and Pharmacy 2012;(24):3683-3685
Objective To explore the characteristics of clinical symptoms and serum brain-derived neurotrophic factor(BDNF)level between depressive patients with and without attempted suicide behavior.Methods Serum BDNF level in depressive patients with(n=36)and without(n=55)attempted suicide behavior were assayed by ELISA,the severity of depression was measured by Hamilton rating scale for depression(HAMD).Results HAMD24 total scores(t=3.632,P=0.000),cognitive disturbance(t=-2.339,P=0.019)and hopelessness factor scores(t=-2.812,P=0.005)in depressive patients with attempted suicide behavior were significantly higher than those in depressive patients without attempted suicide behavior.There were no significant differences of anxiety/somatization,body weight,diurnal variation,psychomotric inhibition and sleeping disturbance fator scores between two groups(P>0.05).The serum BDNF level in depressive patients with attempted suicide behavior was significantly lower than that in depressive patients without attempted suicide behavior(t=-2.122,P=0.037).There was no significant difference of serum BDNF level between male and female patients(P>0.05).Conclusion There were certain characteristics on clinical symptoms of depressive patients with attempted suicide behavior.The low serum BDNF level might play an important role in the risk of suicide in depressive patients.
9.Application of virtual simulation technology to laboratory medicine
Tao QI ; Xiaowen TONG ; Jiyu ZHANG ; Haixia LI ; Yurong QIU ; Qian WANG ; Lei ZHENG
Chinese Journal of Laboratory Medicine 2015;(10):716-718
Medical virtual simulation teaching environment is an advanced and complex combination of virtual simulation technology and medical technology training .As an advanced information technology , it has been attracting the attention of medical education researchers .Based on the characteristics of medical laboratory technology education , the virtual simulation experimental teaching center was established and a framework of the virtual simulation training environment was designed in the Department of Laboratory Medicine, Southern Medical University .Virtual simulation softwares and tool softwares were put into use widely in our experimental teaching .As it turns out, this simulated training environment has many merits such as risk-free safety , great efficiency , genuine learning experience and wide application potential , which partly overcomes the restriction of the teaching process brought by the condition of the practical operation and improves the teaching effect significantly .
10.Comprehensive effect of subglottic secretion drainage on patients with mechanical ventilation in ICU:a Meta-analysis
Xiaowen SUN ; Jiale ZHANG ; Ting JIANG ; Rui TANG ; Xia CHEN ; Fen LIU ; Kejian QIAN ; Rong JIANG
Chinese Critical Care Medicine 2017;29(7):586-591
Objective To systematically evaluate the comprehensive effect of subglottic secretion drainage (SSD) on patients with mechanical ventilation (MV) in intensive care unit (ICU). Methods The randomized controlled clinical trials (RCTs) comparing SSD (intervention group) versus non-SSD (control group) in adult patients with MV in ICU was collected through the databases such as the PubMed database of the National Library of Medicine, CNKI, Wanfang database and the Chinese journal of science and technology database (VIP). The subjects were ICU patients with MV, and the retrieval time ranged from January 2006 to December 2016. Two reviewers independently screened the studies according to the inclusive and exclusive criteria, extracted the data, and assessed the quality. Then RevMan 5.3 software was used for Meta-analysis. Sensitivity analysis was performed using Stata 11.0 software. Funnel plot was used to analyze publication bias. Results In the 1004 documents obtained from preliminary screening, a total of 13 studies involving 2052 patients were enrolled after excluding duplicated documents and literature did not meet the inclusion criteria, with 1021 patients in intervention group, and 1031 in control group. Meta-analysis showed that compared with control group, the application of SSD in patients with MV could contribute to the reduction of the incidence of ventilator-associated pneumonia [VAP; risk ratio (RR) = 0.54, 95% confidence interval (95% CI) = 0.46-0.64, P < 0.00001], the duration of MV [mean difference (MD) = -3.29, 95%CI = -4.53 to -2.05, P < 0.00001] and length of hospital stay (MD = -4.27, 95% CI = -7.36 to -1.18, P = 0.007) were shortened, while there was no significant difference in ICU or hospital mortality rate between the intervention group and control group (RR = 0.89, 95%CI = 0.73-1.09, P = 0.25). The sensitivity analysis for studies enrolled in Meta-analysis of MV duration showed that individual research results were stable through step remove of the included literatures and combined calculation of the remaining literature value, suggesting that individual research results were stable, and would not have a significant impact on the overall results. The results of the funnel analysis showed that there was a symmetry in the inclusion studies, and no significant publication bias was found. Conclusions SSD did have effect in reducing the incidence of VAP, shortening the duration of MV and length of hospital stay, while there was no significant effect on reducing mortality rate. Effective use of SSD is an important measure to prevent VAP. It is necessary to objectively evaluate the clinical effect of SSD.