Myeloid-derived suppressor cells aggravate Sjögren's syndrome by inhibiting the response of Th2 cells / 医学研究生学报

Objective Changes in the number and function of myeloid-derived suppressor cells (MDSC) were reported in clinical and experimental Sjögren’s syndrome (SS), whereas the underlying mechanisms of MDSCs in SS remain to be elucidated. This study was to observe the changes in the pathologic structure and function of the submandibular gland and salivary flow in SS mice after adoptive transfer or deletion of MDSCs and explore the action mechanisms of MDSCs. Methods Ten 4-week-old non-obese diabetic (NOD) mice (without SS-like symptoms) received adoptive transfer of purified MDSCs at 1×106 per mouse (the MDSC group, n = 5) or injection of PBS (the PBS group, n = 5). Another ten 10-week-old NOD mice were injected intraperitoneally with anti-Gr1 antibodies (the anti-Gr1 group, n = 5) or commensurable Rat IgG2b isotype antibodies (the Rat IgG2b group, n = 5). At 2 weeks after treatment, we determined the salivary flow rate, examined lymphocytic infiltration in the submandibular glands, and counted the MDSCs on Th2 cells in different groups of the mice. Results Compared with the PBS group, the NOD mice of the MDSC group showed significantly reduced Th2 cells in the peripheral blood ([0.67 ± 0.13] % vs [0.16 ± 0.07] %, P < 0.05) and spleen ([0.80 ± 0.13] % vs [0.37 ± 0.04] %, P < 0.05) and salivary flow ([78.70 ± 6.80] vs [33.85 ± 11.25] µL, P < 0.05), but increased numbers of MDSCs in the peripheral blood ([1.54 ± 0.14] vs [5.47 ± 1.54] ×105, P < 0.05) and spleen ([1.09 ± 0.23] vs [4.50 ± 1.04] ×105, P < 0.05). In comparison with the Rat IgG2b group, the animals of the anti-Gr1 group exhibited remarkably decreased Th2 cells in the peripheral blood ([0.55 ±0.09] % vs [0.92 ± 0.10] %, P < 0.05) and spleen ([0.63 ± 0.08] % vs [1.10 ± 0.06] %, P < 0.05) and salivary flow ([56.48 ± 14.18] vs [121.20 ± 10.34] µL, P < 0.05), as well as decreased numbers of MDSCs in the peripheral blood ([1.53 ± 0.12] vs [0.35±0.16] ×105, P < 0.05) and spleen ([2.53 ± 1.10] vs [0.91±0.07] ×105, P < 0.05). The adoptive transfer of MDSCs aggravated while the injection of anti-Gr1 antibodies attenuated lymphocytic infiltration in the submandibular gland of the mice. Conclusion MDSCs participate in the pathogenesis Sjögren’s syndrome by suppressing the response of Th2 cells, which suggests that increasing the response of Th2 cells by inhibiting MDSCs could be a novel target for the treatment of Sjögren’s syndrome.

Safety and Effectiveness of High Dose Tigecycline for Treating Patients with Acute Leukemia after Ineffctiveness of Carbapenems Chemotherapy Combinating with Febrile Neutropenia: Retrospective study / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To investigate the safety and efficacy of high dose tigecycline for treatment of fibric neutrope-nia in acute leukemia patients after ineffectiveness of carbapenems chemotherapy of acute leukemia.</p><p><b>METHODS</b>The clinical data of 41 acute leukemia patients with febrile ncutropenia received high dose tigecycline (100 mg q12h), who showed ineffectiveness of treatment with carbapenems, from 20151.30-2017.1. 29 in our hospital were collected and analyzed retrospectively. The temperature, inflammatory indicators as well as hepatic and renal function before and after treatment with tigecycline were compared.</p><p><b>RESULTS</b>Among 41 patients treated with tigecycline due to ineffectiveness of treatment with carbapenems, the infection had been controled in 34 cases, 7 patients died due to ineffectiveness of anti-infective treatment, these patients all were patients with relapse/refractory leukemia. 41 patients were examined etialogically, as a result, 22 patients showed possitive, among them the gram-negative bacill was found in 11(11/22) cases. The average deferves counce time of tigecycline was 28.2±12.0 hours. The temperature of patients treated with tigecycline for 48 hours decreased significantly (P<0.05). There were no significant differences in calcitonin and C-reactive protein levels after treatment with tigecycline (P>0.05), but cacitonin level displayed decrease tread. There was no hepatic and renal impairment after treatment with tigecycline, but levels of as partate aminotransferase, total bilirubin and blood area nitrogen in blood significantly increased as compared with levels before treatment with tigecycline (P<0.05).</p><p><b>CONCLUSION</b>The application of high dose tigecycline for treatment of febrile neutropenia is safety and effective. The high dose tigecycline can decrease the temperature, calcitonin and C-reactive protein levels, and can control infection without the hepatic and renal impairment, but it needs to be confimed by more prospective studies.</p>

Pathogenesis of t(8;21) acute myeloid leukemia and the progress of next generation sequencing technique in leukemia / 解放军医学杂志

Acute myeloid leukemia (AML),the most common disease in acute leukemia,is a highly heterogeneous invasive hematological disease.The t(8;21)(q22;q22) translocation is the most common chromosomal translocation in AML,generating AML1-ETO fusion gene and encoding AML1-ETO fusion protein.This article summarizes the two-hit hypothesis in AML occurrence,the pathogenesis of t(8;21)AML,all features involved in t(8;21)AML,and the function of the components in AML1-ETO fusion protein,providing important basic information for the treatment and prognosis of t(8;21)AML.Meanwhile,this article also summarizes the progress of next generation sequencing technique in leukemia,providing a new technique for the accurate therapy of (8;21)AML.

Sling Exercise for Chronic Non-Specific Low Back Pain:A Meta-analysis / 中国康复理论与实践

Objective To systematically review the clinical efficacy of sling exercise therapy(SET)on patients with chronic non-specif-ic low back pain (CNLBP). Methods Randomized controlled trials (RCT) about SET for CNLBP were electronically searched in CNKI, VIP,Wanfang Data,PubMed,Web of Science,The Cochrane Library and Embase from June,2007 to June,2017.After literatures screening, data extraction,quality evaluation and risk assessment,the results of meta-analysis were conducted by RevMan 5.3 software.Results Final-ly, 15 RCTs involving 789 patients were included. SET was better in improving Visual Analogue Scale (VAS) score (MD=-1.15, 95% CI[-1.41,-0.90],Z=8.82,P<0.00001)and Oswestry Low Back Pain Disability Index(ODI)score(MD=-1.29,95%CI[-1.80,-0.78],Z=4.94, P<0.00001) than physical therapy, and was better than other exercise therapies in improving the VAS score (MD=-0.94, 95% CI[-1.52,-0.37],Z=3.21,P=0.001)and ODI score(MD=-5.96,95%CI[-9.41,-2.51],Z=3.38,P=0.0007).However,no significant dif-ference was found in improving the NPRS score between SET and other exercise therapies(MD=0.35,95%CI[-0.23,0.93],Z=1.19,P=0.23),nor in improving VAS score between SET and traditional Chinese medical therapies(MD=-5.29,95%CI[-20.27,9.70],Z=0.69,P=0.49).Conclusion SET may play a role in relieving pain and functional limitations in patients with CNLBP.Due to the limited quantity and quality of the included studies,larger scale and high quality RCTs are needed to verify the aforementioned conclusion.

miRNA-101-3 p inhibits proliferation and migration of gastric cancer cells by targeting EZH2 / 中国病理生理杂志

AIM:To investigate the role of microRNA-101-3p (miRNA-101-3p) on the proliferation, apopto-sis and invasion of gastric cancer cells and the possible regulatory mechanisms .METHODS: The expression of miRNA-101-3p in two kinds of gastric cancer cells and a gastric mucosal cell line was detected by real -time PCR.The miRNA-101-3p was overexpressed by Lipofectamine 2000 transfection with miRNA-101-3p mimics.The effects of miRNA-101-3p on cell cycle distribution and apoptosis were analyzed by flow cytometry .The effects of miRNA-101-3p on cell proliferation and migration abilities were detected by CCK-8 assay, trypan blue exclusion test and Transwell assay .The protein expression of enhancer of zeste homolog 2 ( EZH2) was determined by Western blot .RESULTS: The expression of miRNA-101-3p in gastric cancer cells was lower than that in gastric mucosal cells (P<0.05).The gastric cancer cell MGC-803 had the low-est expression level of miRNA-101-3p.The result of flow cytometry showed that the population of S phase was reduced , and the population of G0/G1 phase and the early stage apoptotic rate were increased after the expression of miRNA-101-3p was overexpressed (P<0.05).The results of CCK-8 assay, trypan blue exclusion test and Transwell assay showed that overex-pression of miRNA-101-3p significantly reduced the proliferation and migration abilities of gastric cancer cells (P<0.05). Overexpression of miRNA-101-3p decreased the protein level of EZH2 (P<0.05).CONCLUSION:miRNA-101-3p may suppresses the gastric cancer cell proliferation and migration , and promotes the gastric cancer cell apotosis by down-regula-tion of EZH2.

Epigenetic Silencing of Eyes Absent 4 Gene by Acute Myeloid Leukemia 1-Eight-twenty-one Oncoprotein Contributes to Leukemogenesis in t(8;21) Acute Myeloid Leukemia / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The acute myeloid leukemia 1 (AML1)-eight-twenty-one (ETO) fusion protein generated by the t(8;21)(q22;q22) translocation is considered to display a crucial role in leukemogenesis in AML. By focusing on the anti-leukemia effects of eyes absent 4 (EYA4) gene on AML cells, we investigated the biologic and molecular mechanism associated with AML1-ETO expressed in t(8;21) AML.</p><p><b>METHODS</b>Qualitative polymerase chain reaction (PCR), quantitative reverse transcription PCR (RT-PCR), and Western blotting analysis were used to observe the mRNA and protein expression levels of EYA4 in cell lines. Different plasmids (including mutant plasmids) of dual luciferase reporter vector were built to study the binding status of AML1-ETO to the promoter region of EYA4. Chromatin immunoprecipitation assay was used to study the epigenetic silencing mechanism of EYA4. Bisulfite sequencing was applied to detect the methylation status in EYA4 promoter region. The influence of EYA4 gene in the cell proliferation, apoptosis, and cell clone-forming ability was detected by the technique of Cell Counting Kit-8, flow cytometry, and clonogenic assay.</p><p><b>RESULTS</b>EYA4 gene was hypermethylated in AML1-ETO+ patients and its expression was down-regulated by 6-fold in Kasumi-1 and SKNO-1 cells, compared to HL-60 and SKNO-1-siA/E cells, respectively. We demonstrated that AML1-ETO triggered the epigenetic silencing of EYA4 gene by binding at AML1-binding sites and recruiting histone deacetylase 1 and DNA methyltransferases. Enhanced EYA4 expression levels inhibited cellular proliferation and suppressed cell colony formation in AML1-ETO+ cell lines. We also found EYA4 transfection increased apoptosis of Kasumi-1 and SKNO-1 cells by 1.6-fold and 1.4-fold compared to negative control, respectively.</p><p><b>CONCLUSIONS</b>Our study identified EYA4 gene as targets for AML1-ETO and indicated it as a novel tumor suppressor gene. In addition, we provided evidence that EYA4 gene might be a novel therapeutic target and a potential candidate for treating AML1-ETO+ t (8;21) AML.</p>

A Retrospective Study of Ph Negative Adolescent and Young Adults with Acute B Lymphoblastic Leukemia in Two Centers / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To analyze the therapeutic efficacy of different consolidation therapies after induction remission on Ph negative adolescent and young adults with acute B lymphoblastic leukemia, and to explore the effect of different risk factors on prognosis.</p><p><b>METHODS</b>The treatment and efficacy of 80 Ph negative B-ALL in patients of 16-39 years old in the Hematology Department of 301(65 cases) and 309(15 cases) hospital from 1999 to 2016 are retrospectively analyzed. The patients received combined induction chemotherapy of 4 or 5 chemotherapeutic drugs (VDCLP/ VDLP/ DOLP/ IOLP). After remission patients received consolidation protocols of 3-5 cycls, and then received allo-HSCT or haploidentical HSCT. The median follow-up time was 29 (6-153) months.</p><p><b>RESULTS</b>HSCT was carried out after CR1. The 5-year OS and EFS of allo-HSCT group(n=29) was (73±16)% and (67±17)%, respectively, while those of haploidentical-HSCT group(n=20) were (53±22)% and (53±22)%, respectively, and those of pediatric-inspired protocols(n=31) was (63±17)% and (50±18)%, respectively. The difference between OS and EFS in 3 group was not statistically significant(P>0.05). The re-remission rate of recurrent patients was (50±23)%. On the one side, the cumulative incidence of TRM of pediatric-inspired protocol was better than that of HSCT (P<0.05). On the other side, the cummulative incidence of relapse (CIR) of pediatric-inspired protocol was poorer than that of HSCT, yet without significant difference (P>0.05). The median remission time of CR2 in patients was 14(2-36) months. Univariate and multivariate analysis were performed in 65 patients, and showed an abnormal result of CD13 or CD33 positive, CD22 negative, indicating a poor prognosis(P<0.05).</p><p><b>CONCLUSION</b>In the adolescent and young adult patients with PhB-ALL treated by pediatric-inspired protocols, the survival time is similar with that in allo-HSCT group. However, more prospective clinical studies of random control test(RCT) should be carried out.</p>

Study on deficits of switching function in video game addicts / 重庆医学

Objective To study the characteristics of the deficits of switching function in video game addicts .Methods A total of 21 game addicts and 21 normal participants were performed a classic task switch task ,then the switching cost between two groups was compared .Results The results showed that the switching cost was significant greater for game addicts (372 ms) than that for health participants(180 ms) ,t=3 .63 ,P<0 .05 .Conclusion The present study suggested that the switching function was impaired to a certain extent for video game addicts ,and it might be one of the cognitive mechanisms for causing the game addicts .

Prognostic significance of detecting MLL-AF9 fusion gene expression in patients with acute myeloid leukemia by real-time fluorescence quantitative PCR / 中国实验血液学杂志

<p><b>UNLABELLED</b>This study was aimed to explore the value of detecting the expression levels of MLL-AF9 (mixed lineage leukemia, MLL) fusion gene during the treatment of acute myeloid leukemia (AML) by real-time fluorescence quantitative PCR (RQ-PCR), and to evaluate its prognostic significance in monitoring minimal residual disease (MRD). The expression levels of 11 patients with MLL-AF9 fusion gene positive were detected precisely by RQ-PCR during the treatment in order to analyze the correlation of detection results with clinical manifestations. The results showed that the expression levels of MLL-AF9 fusion gene in patients at initial diagnosis were 1.3%-55.28%.</p><p><b>RESULTS</b>obtained from 5 patients who received chemotherapy alone during the interval between first and second courses of chemotherapy indicated that 2 patients with <0.1% of MLL-AF9 fusion gene expression levels all achieved hematologic complete remission and survived, while the remaining 3 patients with ≥ 0.1% of MLL-AF9 fusion gene did not achieve hematologic complete remission and only 1 case survived. Moreover, results obtained from 6 transplant patients within a month before the transplantation suggested that 4 of them with < 0.1% of MLL-AF9 fusion gene expression levels survived without relapses, while the remaining 2 patients with ≥ 0.1% of MLL-AF9 fusion gene expression levels relapsed and died. Besides, MLL-AF9 fusion gene expression levels were ≥ 0.1% within one month before the morphological relapse of bone marrow in 2 recurrent patients. It is concluded that the detecting the expression level of MLL-AF9 fusion gene by RQ-PCR is an effective and accurate method to quantify and monitor the MRD level of MLL-AF9 gene positive AML patients and may be used for early detecting molecular relapse of AML.</p>