STING1 in sepsis: Mechanisms, functions, and implications / 中华创伤杂志(英文版)

Sepsis is a life-threatening clinical syndrome and one of the most challenging health problems in the world. Pathologically, sepsis and septic shock are caused by a dysregulated host immune response to infection, which can eventually lead to multiple organ failure and even death. As an adaptor transporter between the endoplasmic reticulum and Golgi apparatus, stimulator of interferon response cGAMP interactor 1 (STING1, also known as STING or TMEM173) has been found to play a vital role at the intersection of innate immunity, inflammation, autophagy, and cell death in response to invading microbial pathogens or endogenous host damage. There is ample evidence that impaired STING1, through its immune and non-immune functions, is involved in the pathological process of sepsis. In this review, we discuss the regulation and function of the STING1 pathway in sepsis and highlight it as a suitable drug target for the treatment of lethal infection.

Brief analysis on pivot effect of Tianshu (ST 25) / 中国针灸

The pivot effect of Tianshu (ST 25) was analyzed, which was explored from 5 aspects, named the ascending and descending of spleen and stomach

The practice of multidisciplinary team model in cancer diagnosis and treatment in the primary hospitals / 中华普通外科杂志

Objective To introduce and analyze the status of tumor multidisciplinary team (MDT) model application in primary hospitals.Methods MDT discussion decision-making and implementation of Nanpi People's Hospital from June 2013 to July 2015 were retrospectively analyzed.Results A total of 251 cases were recruited into the MDT discussion.Among them,233 primarily diagnosed cases reached MDT decision-making and 159 cases took the decision,118 cases achieved the purpose (74.2％),41 cases failed (25.8％).Yet in 74 cases not following the decision,11 cases achieved the desired purpose (14.9％),while 63 cases didn't meet the desired purpose (85.1％),the difference was statistically significant (x2 =71.97,P ＜ 0.01).Ultrasound interventional biopsy,enhanced CT scan,CT guided puncture,intraoperative frozen section examination in malignant tumor patients had significantly increased after MDT applied,the difference was statistically significant (all P ＜ 0.05).The annual new rural cooperative medical system referral rate in malignant tumor patients dropped sharply (x2 =19.86,P ＜ 0.01) Conclusions Doctors and cancer patients can benefit from MDT diagnosis and treatment model,which is worth generalization.

The application of dual-source Flash post-processing software for the evaluation of bronchial artery / 实用放射学杂志

Objective To evaluate feasibility and time efficiency of dual-source flash post-processing software (Bone Reading)for reconstruction of bronchial artery.Methods The imaging data of 70 patients with suspected bronchial artery dilatation who underwent bronchial artery-CTA were evaluated by 2 independent radiologists.First,the related contents of bronchial artery such as origination,number, type,route and lumen diameter were evaluated by multiple planar reconstruction (MPR),maximum intensity projection (MIP)and volume rendering technique (VRT).The results and process time were recorded.After a month,the post-processing software(Bone Reading)was used to evaluate the same contents.Results There was very good correlation between both readers for both reading methods without significant differences.There was significant difference of process time between with regular method and with Bone Reading (P<0.05)for both readers.Process time could be decreased by approximately 35%.Conclusion The application of CT software (Bone Reading)is feasible in the CTA of bronchial artery.This method may gain a significant time saving in comparison to regular method.

Application of 70 kV with 30 mL contrast medium by dual-source CT with Stellar photon detector in coronary angiography / 实用放射学杂志

Objective To investigate the value of prospectively electrocardiogram (ECG)-triggered high-pitch coronary computed tomography angiography at 70 kV and 30 mL contrast medium with Stellar detector dual-source CT.Methods 60 patients with the BMI0.05).The CT attenuation of the 70 kV group were higher than that of the 100 kV group for all the segments(P 0.05).Compared with the 100 kV group,the radiation dose of the 70 kV group was reduced by 76.5% (A:0.19±0.023 mSv,B:0.81±0.101 mSv,P <0.01).Conclusion Using 70 kV with 30 mL contrast medium in Stellar detector dual-source CT coronary angiography for the patients with a normal BMI could obtain qualified diagnostic image with low radiation dose and contrast medium.

Models and methods of failure analysis and risk assessment during medical treatment / 中国组织工程研究

BACKGROUND:Medical risks are al unsafe events or that damage to the patient during medical services. Present medical risk management is mainly qualitative experience, and lacks of regular failure analysis and risk assessment for established medical treatment. OBJECTIVE:To construct models of medical process failure analysis and risk assessment, find possible risks during medical treatment, and propose effective measures to eliminate or decrease above risks. METHODS:Failure mode and effects analysis during reliability engineering were used in production. That was, risk assessment was conducted in the possible technical failure modes, causes and al impacts on the product during each process. Improvement measures were made for weak link during the process. The risk could reach an acceptable level. In accordance with failure mode and effects analysis during production, the procedure of medical process failure analysis and risk assessment could be made to analyze the potential failures during medical treatment. Moreover, the improvement measures were proposed for weak link with high risks so as to prevent the occurrence of risk of significant adverse effects on patients. RESULTS AND CONCLUSION:The methods and basic procedures of medical process failure analysis and risk assessment were established by using the experience of failure mode and effects analysis. Taking the rescue process of myocardial infarction in the emergency of a hospital as an example, the analysis of failures, reasons and impacts was performed taking“chewing 300 mg aspirin”in the rescue steps as a key. The improvement measures and suggestions were proposed for unacceptable failures and reasons. Seen from the analysis results, proposed improvement measures and suggestions can obviously decrease the risks of failures caused by this step to patients. Therefore, the application of failure mode and effects analysis in medical treatment has a strong practical value.

Effect of RelB on HIV-1 Vpr-mediated transcription activation and cell G2/M arrest / 病毒学报

Vpr, an auxiliary protein of HIV-1(Human immunodeficiency virus type 1), exerts important functions to promote viral replication and AIDS progression. In this study, we performed a yeast two-hybrid screening assay using human cDNA library to further investigate the molecular mechanism of various functions of Vpr RelB, a key protein in NF-kappaB signaling pathway, was identified as a Vpr interaction protein by co-immunoprecipitation. Further investigations indicated that RelB not only promoted the Vpr-mediated activation of NF-kappaB reporter gene, but also enhanced the transactivation of HIV LTR. Moreover, the results showed that RelB promoted Vpr-induced cell cycle G2/M arrest. Collectively, these results indicated that RelB might interact with Vpr and regulate its transcriptional activation and cell cycle arrest.

The clinical pathological analysis of 14 autopsy cases of pneumoconiosis / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To investigate the histopathological features, complications, diagnosis, and differential diagnosis of coal workers' pneumoconiosis (CWP).</p><p><b>METHODS</b>The lung tissue sections from 14 autopsy cases of CWP were subjected to HE staining and observed under a light microscope, and a retrospective analysis was performed considering the occupational history and clinical features.</p><p><b>RESULTS</b>The 14 cases were 46-71 years of age (mean, 57.7 years). Two cases were diagnosed as dust reaction, 1 case as simple CWP (stage I anthracosilicosis), and 11 cases as complicated CWP (9 cases of stage II anthracosilicosis, 1 case of stage III anthracosilicosis, and 1 case of stage III silicosis). Twelve cases were complicated by chronic bronchitis and emphysema, 8 cases by pulmonary heart disease, 4 cases by pulmonary tuberculosis, 3 cases by liver cirrhosis and liver cancer with pulmonary metastases, and 2 cases by cerebral hemorrhage.</p><p><b>CONCLUSION</b>Among patients with CWP, the pathological changes of lung tissue become more complex with increasing years of dust exposure. Coal macule is the common pathological feature of CWP, and dust nodules and massive fibrosis are the necessary indices of pathological diagnosis.</p>

Pathologic observation on animal model of silicosis / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To explore the pathological changes of pulmonary fibrosis induced by SiO2 in rats and pigs.</p><p><b>METHODS</b>The silicosis models in rats and pigs were established by non-exposure method. The pathologic changes in lung tissues of rats and pigs were observed with HE staining under a light microscopy and under a transmission electron microscopy (TEM), the expression of cytokines was detected by immunohistochemistry.</p><p><b>RESULTS</b>(1) The main pathologic changes of silicosis models in rats and pigs included: in 7 ∼ 15 days after treatment, silica dusts, dust cells, a lot of macrophages, lung epithelial cells, a few neutrophils, macrophage alveolar inflammation and nodules of stage I were found in alveolar space; in 30 ∼ 90 days after treatment, many nodules of stage I-III or IV with lymphocytes infiltration were observed in respiratory bronchioles, alveoli, interlobular septa, the subpleural and around blood vessels and bronchi. (2) The expression levels of CK protein, SP-A protein, CD68, b-FGF, TNF-α, IL-6, TGF-β1, NFKappa/P50, Kappa/P65 and VEGF reduced with exposure time, but still were higher than those of the control. (3) The shed alveolar type I cells, proliferation of alveolar type II cells or macrophages and activated cellular function induced by silica were observed under TEM.</p><p><b>CONCLUSION</b>The development of pulmonary fibrosis in silicosis models corresponded with the process from macrophages alveolar inflammation to pulmonary fibrosis.</p>

Detection of bone marrow involved by nonhematopoietic neoplasms using flow cytometry / 中华检验医学杂志

Objective To study the value of flow cytometry in identifying metastatic CK positive and negative nonhematopoietic neoplasms in bone marrow. Methods Twenty-six cell lines representing ten epithelial neoplasms, one lymphoma cell line and one human T cell lymphoblast-like cell line were purchased from American Tissue Culture Collection. From July 2009 to June 2010, five nonhematopoietic neoplasms,fifteen hematopoietic neoplasms and fifteen control patients with complete remession after hematopoietic stem cell transplantation were collected in Beijing Daopei Hospital. Cryopreserved cell lines were thawed and cultured until they entered log phase. After permeabilization, cell lines were analyzed by staining with cytoplasmic CK-FITC antibody using four-color flow cytometer. The percent CK positivity was measured by comparing with negative control. Bone marrow samples were stained with membrane and cytoplasmic antibodies according to our routine methods. Based on lineage markers and blast markers as well as CK expression, the relevant hematopoietic diseases were diagnosed or excluded according to 2008 World Health Organization diagnosis standards. Results All epithelial neoplasm cell lines expressed CK, with average positive percentage 81.1%. All the lymphoid tumor cell lines didn't express CK. Two epithelial neoplasms were CK positive, 100. 0% in thyroid carcinoma and 98. 2% in lung carcinoma, respectively. Hematopoietic tumor and control samples didn't express CK. They expressed relevant hematopoietic markers, such as CD45 as well as lineage markers, or CD138 and cytoplasmic immunoglobulin light chain. Three nonepithelial nonhematopoietic neoplasms didn't express CK. CK positive or negative nonhematopoietic neoplasms didn't express hematopoietic markers such as CD45, HLA-ABC and HLA-DR DP DQ, as well as lineage specific markers. Besides, CK positive might be helpful to suggest epithelial origin. Conclusion Flow cytometry with hematopoietic markers and CK can effectively exclude hematopoietic tumor and identify metastatic CK positive and negative nonhematopoietic neoplasms in bone marrow.

Evaluation of polymorphic post-allotransplant lymphoproliferative disorder by flow cytometry / 中华血液学杂志

<p><b>OBJECTIVE</b>To study the role of flow cytometry (FCM) in detection of polymorphic post-transplant lymphoproliferative disorders (PTLD).</p><p><b>METHODS AND RESULTS</b>Two patients presented with fever and multiple lymphadenopathy on day 46 and day 50 respectively after successful allogeneic hematopoietic stem cell transplantation (allo-HSCT). The symptoms couldn't be controlled by antibiotics. The polymorphic PTLD was diagnosed based on the elevation of bone marrow EB virus DNA and detection of subsets of light chain restricted B cells and/or plasma cells in peripheral blood (PB) samples. The lymphocyte immunophenotypes from PB and/or bone marrow (BM) samples were serially tested by FCM after lowering the dose of immunosupressive agents and treating with antivirus drugs, anti-CD20 antibodies, and cytotoxic T cell infusion. B cells were undetable in two patient, but monoclonal plasma cells appeared or maintained. One patient died after two weeks. Another patient was still on treatment. B cells and plasms cells couldn't be detected in her PB, but there were monoclonal plasma cells in her BM. FCM have a prominent advantage in detect polymorphic PTLD, since it can effectively recognize different cell groups in blood and identify monoclonal subsets. Besides, the immunophenotype of plasma cells in polymorphic PTLD might be different from that in typical plasma cell myeloma.</p><p><b>CONCLUSION</b>Polymorphic PTLD can be detected and followed up by FCM. BM is more suitable than PB for monitoing the disease. Besides lymph node biopsy, B cell abnormaliity could be detected in PB in allo-HSCT patients.</p>

Changes of T-cell clonality after induction-cultivation of peripheral T lymphocytes in adoptive immunotherapy for leukemias / 中国实验血液学杂志

This study was purposed to analyze the changes of T-cell clonality after induction of peripheral T lymphocytes by autogenous DC and cytokines in the preparation of adoptive immunotherapy for leukemias. The bone marrow and peripheral blood from 21 leukemia patients at remission stage after treatment and subjected to adoptive immunotherapy were collected. Their DCs and T-cells were stimulated with cytokines and then were mixed to activate T-cells. T-cell receptor beta variable region (TCRBV) families were amplified by RT-PCR, and genescan method and sequencing of the PCR products were used to observe the clonality changes of T-cells before and after the induction and cultivation of T-cells. The flow cytometry was used to identify CD3(+), CD4(+), CD8(+), CD3(+)CD56(+) and CD4(+)CD25str(+)FOXP3(+) cells to disclose the ratio change of cytotoxic T lymphocytes (CTL), helper T-cells, regulatory T-cells and NK T-cells before and after induction and cultivation of T-cells. The results showed that in the 21 patients, most of the 24 TCRBV families presented as oligoclonal distribution on genescan, several families were not expressed, and only a few families remained polyclonal. TCRBV24 was found to be oligoclonal in all of the 21 patients. DNA sequence analysis of TCRBV24 revealed a common motif of VAG in CDR3 in 3 cases and a common motif of GGG in CDR3 in 2 cases. In patient 5, both TCRBV 24 and TCRBV8 contained the same motif of GGG in CDR3. The identical motif in these patients may suggest that these T-cells recognize the same antigen. The peripheral lymphocytes demonstrated recovery of clonal profile on genescan from oligoclonal profile and absence of several families before the induction and cultivation to typical polyclonal profile in all TCRBV families after the induction by DC and cytokines for 13 days. After the induction and cultivation, the number of lymphocytes increased to 3.38 +/- 1.20 times. CD3(+), CD4(+), CD8(+), CD3(+)CD56(+) and CD4(+)CD25str(+)FOX P3(+) cells were 71.1 +/- 11.8%, 26.7 +/- 11.4%, 35.7 +/- 12.9%, 3.1 +/- 1.6% and 0.12 +/- 0.1% respectively before the induction and cultivation, and changed to 95.4 +/- 3.2% (p < 0.01), 27.0 +/- 13.1% (p > 0.01), 55.5 +/- 13.8% (p < 0.01), 9.8 +/- 6.1% (p < 0.01) and 0.22 +/- 0.18% (p < 0.01) respectively after the induction and cultivation. It is concluded that the major action of this induction and cultivation method on T-lymphocytes in vitro is the promotion of CTL and NK T-cell proliferation. In leukemic patients at the remission stage, the TCRBV profile is characterized by the oligoclonal proliferation of T-lymphocytes. Several proliferated clones may have the same motif in CDR3, suggesting the recognition of the same antigen by these lymphocyte clones. Cytokine induction and co-culture with autogenous DCs can stimulate the T-lymphocytes to recover their immunocompetence as manifested by the polyclonal profile and the proliferation of CTL and NK-T cells.

Expression of WAVE1 in childhood acute lymphocytic leukemia and in the apoptosis of Jurkat cells induced by adriamycin / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To investigate whether WASP/Verprolin homologous protein 1 (WAVE1) plays a role in the pathogenesis of childhood acute lymphoblastic leukemia (ALL).</p><p><b>METHODS</b>WAVE1 mRNA and protein expression in bone marrow mononuclear cells (BMMCs) was measured by RT-PCR and Western blotting respectively in 4 children with ALL relapse, 15 children with ALL in complete remission (CR) and 40 children with newly diagnosed ALL. Ten normal bone marrow samples were used as controls. Jurkat cells were treated with different concentrations of adriamycin (ADM). The cell proliferation was detected with MTT. The apoptosis rate was measured by flow cytometry. WAVE1 mRNA and protein expression of Jurkat cells treated with ADM was detected by RT-PCR and Western blotting respectively.</p><p><b>RESULTS</b>WAVE1 was not expressed or weakly expressed in BMMCs from normal controls and patients with ALL in CR. Higher WAVE1 mRNA and protein expression was found in BMMCs from patients with newly diagnosed ALL and patients with relapse ALL when compared with the controls and the patients in CR (P<0.01). ADM significantly inhibited the proliferation of the Jurkat cells and the inhibitory effect was dose-and time-dependent (P<0.05). After ADM treatment for 24 hrs, the percentage of apoptosis cells increased significantly and WAVE1 mRNA and protein expression of Jurkat cells decreased significantly when compared with the untreated controls (P<0.05).</p><p><b>CONCLUSIONS</b>The WAVE1 expression increased in children with ALL. WAVE1 may be related to the development of ALL and may be severed as a marker for the evaluation of the severity of ALL in children.</p>

Enhancive effect of HMGB1 gene silence on adriamycin-induced apoptosis in K562/A02 drug resistance leukemia cells / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate the effect of high mobility group boxl (HMGBI) gene silence on adriamycin (ADM)-induced apoptosis in K562/A02 drug resistance leukemia cells.</p><p><b>METHODS</b>K562/ A02 cells were transient transfected with HMGB1- small interference RNA(siRNA) vector, and the levels of HMGB1 gene differential expression pre-and post-transfection were measured by RT-PCR and Western blotting. 50% inhibition concentration (IC50) of ADM on K562/A02 was determined by WST-8 assay. Cell apoptosis was assessed by flow cytometry. The release of Smac/DIABLO from the mitochondria to the cytoplasm was assayed by Western blotting. Activity of Caspase-3 was assayed with a Caspase Colorimetric Assay Kit.</p><p><b>RESULTS</b>(1) The HMGB1 expression at mRNA and protein levels in HMGB1 siRNA transfected K562/A02 cells were decreased by 86% and 71% respectively compared with control. (2) Suppression of HMGB1 by siRNA in K562/A02 cells resulted in a reversal of the resistance to ADM, and decreased IC50 from (4.83 +/- 0.08) microg/ml to (1.33 +/- 0.10) microg/ml. 1 microg/ml and 5 microg/ml of ADM treatment increased cell apoptotic rate by 27% and 32% respectively. (3) HMGB1 suppression in K562/A02 cells significantly promoted ADM- induced Smac/DIABLO release from the mitochondria to the cytoplasm, and increased the activities of Caspase-3.</p><p><b>CONCLUSION</b>HMGB1 gene silence can enhance sensitivity of K562/A02 cells to ADM and reverse cell resistant to ADM.</p>

Clinical data of childhood leukemia in Hunan Province between 2002 and 2005 / 中国当代儿科杂志

<p><b>OBJECTIVE</b>This study analyzed the clinical data of newly diagnosed childhood leukemia from various hospitals in the cities or counties of Hunan Province between 2002 and 2005 in order to provide references for further epidemiologic survey of childhood leukemia.</p><p><b>METHODS</b>The clinical data of children with newly diagnosed leukemia from hospitals of various cities or counties of Hunan Province between 2002 and 2005 were collected and reviewed.</p><p><b>RESULTS</b>There were 803 children with leukemia during 2002-2005. Acute lymphoid leukemia was most commonly seen (597/803, 74.35%), followed by acute non-lymphoid leukemia (192/803, 23.91%) and chronic myelocytic leukemia (14/803, 1.74%). There were no significant differences in the clinical type and the prevalence of leukemia between males and females. The prevalence of newly diagnosed childhood leukemia in the urban area was noticeably higher than that in the rural area (2.02/10(5) vs 1.50/10(5), P < 0.05). 41.79% of children with newly diagnosed leukemia from the urban area received treatments but only 22.80% of patients from the rural area received treatments (P < 0.05).</p><p><b>CONCLUSIONS</b>This study of patients-based hospitals showed some features of the morbidity of childhood leukemia in Hunan Province. It provides references for further epidemiologic investigation of this disease in Hunan Province.</p>

Role of WAVE1 in drug resistance of K562/A02 leukemia cells / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate if WAVE1 is involved in mult drug-resistance (MDR) of human leukemia cell line K562/A02.</p><p><b>METHODS</b>The level of WAVE1 in K562 and K562/A02 cells was assayed by Western blot and RT-PCR; K562 cells and K562/A02 cells were transient transfected with pEFBOS-WAVE1 reconstructed plasmid or specifically siRNA to WAVE1. 50% inhibition concentration (IC50) of doxorubicin on K562/A02 was determined by WST-8 assay. Hoechst33258 staining was used to examine cell morphological changes and to calculate percentage of apoptotic nuclei. The mRNA level of mdrl was assayed by RT-PCR. The Bcl-2 protein was assayed by Western blot.</p><p><b>RESULTS</b>1. The WAVE1 expression at mRNA and protein level in K562/A02 cells was increased by about 70% and 63% respectively as compared with that in K562 cells. 2. Overexpression of WAVE1 in K562 cells by transient transfection significantly increased the resistance to doxorubicin, and increased IC50 from (0.05 +/- 0.00) microg/ml to (2.99 +/- 0.12) microg/ml, and at 1 microg/ml or 5 microg/ml of doxorubicin treatment, cell apoptotic nuclei rate was decreased by 30% or 35% respectively. 3. Suppression of WAVE1 in K562/A02 cells by siRNA resulted in a reversal of MDR to doxorubicin, and decreased IC50 from (4.29 +/- 0.15) microg/ml to (1.85 +/- 0.07) microg/ml, and at 1 microg/ml or 5 microg/ml of doxorubicin treatment, cell apoptotic nuclei rate was increased by 24% or 21% respectively. 4. Overexpression of WAVE1 in K562 cells significantly increased the mdrl mRNA and the Bcl-2 protein, and suppression of WAVE1 in K562/A02 cells by siRNA decreased the mRNA and the protein.</p><p><b>CONCLUSION</b>WAVE1 involves in the MDR mechanisms in K562/A02 leukemia cells through regulation the level of mdrl and Bcl-2.</p>

High mobility group box 1 is increased in children with acute lymphocytic leukemia and stimulates the release of tumor necrosis factor-alpha in leukemic cell / 中华儿科杂志

<p><b>OBJECTIVE</b>Cytokine mediated cell immunity is the main mode of anti-tumor immunity in organism, and the disequilibrium of cytokine network is the main cause of tumor cells escaping immunologic surveillance. High mobility group box 1 (HMGB1), a nuclear protein, has recently been identified as an important mediator of local and systemic inflammatory diseases when released into the extracellular milieu. In the present study, the investigators explored the clinical significance of alteration in the serum levels of HMGB1 in childhood acute lymphocytic leukemia (ALL) and the mechanism of HMGB1-induced tumor necrosis factor (TNF)-alpha secretion in leukemic cells.</p><p><b>METHODS</b>The serum levels of HMGB1 in healthy children and childhood ALL were assayed by Western blotting. K562 leukemic cells were stimulated with recombinant HMGB1 protein in vitro, and the secretion of TNF-alpha was determined by using ELISA. The effects of HMGB1 on activation of p38, c-Jun amino-terminal kinase (JNK), and extracellular-signal regulated protein kinase (ERK) and mitogen-activated protein kinase (MAPK) in K562 cells were assayed by using Western blotting. The effects of inhibitors specific for the MAPK on HMGB1-induced TNF-alpha secretion were assayed by using ELISA.</p><p><b>RESULTS</b>The serum levels of HMGB1 were significantly higher in ALL initial treatment group (n = 15, 43.78 +/- 4.62 microg/ml) than those in healthy control group (n = 15, 0.60 +/- 0.48 microg/ml, P < 0.01) and ALL complete remission group (n = 15, 0.89 +/- 0.62 microg/ml, P < 0.01). No significant difference was found between the healthy control group and ALL complete remission group in HMGB1 levels (P > 0.05). TNF-alpha started to become detectable at 2 h and was still increasing at 16 h after HMGB1 (1 microg/ml) treatment in K562 cell culture. TNF-alpha was also secreted from K562 cells in a dose-dependent manner after HMGB1 (1 ng/ml-1 microg/ml) exposure. HMGB1 induced the phosphorylation of p38, JNK and ERK in k562 cells. Inhibitors specific for the JNK (SP600125), MEK (PD98059), and p38 MAPK (SB203580), abrogated HMGB1-induced TNF-alpha secretion.</p><p><b>CONCLUSIONS</b>The measurement of serum HMGB1 is helpful to evaluate the prognosis of the childhood ALL. HMGB1 stimulates leukemic cells to secrete TNF-alpha through a MAPK-dependent mechanism.</p>

Allelic loss of 6q16.3 microsatellite DNA in childhood acute lymphoblastic leukemia and bioinformatics analysis / 中华血液学杂志

<p><b>OBJECTIVE</b>To locate the cluster region of loss of heterozygosity (LOH) in children with acute lymphoblastic leukemia (ALL), and explore the new tumor suppressor gene.</p><p><b>METHODS</b>Allelic loss was analyzed by PCR with 15 microsatellite markers mapping on 6q16.3. The LOH was analyzed by bioinformatics. The relationship between LOH and clinical factors was further analyzed.</p><p><b>RESULTS</b>The frequency of LOH at least at one loci on 6q16.3 was 32.7%. The LOH in relapsed patients was higher than those in not relapsed. The higher frequency of LOH was observed in two regions of D6S1709-D6S1028 and D6S2160-D6S1580 at 6q16.3. GRIK2 may be a candidate of tumor suppressor gene. There are 12 ESTs may carry out new anti-oncogene. Patients with 6q LOH had higher WBC counts (P < 0.01), blast cells percentage (P < 0.01), relapse rate (P < 0.05) and chromosomal aberration (P < 0.05).</p><p><b>CONCLUSION</b>D6S1709-D6S1028 and D6S2160-D6S1580 are two regions of minimus deletion on 6q16.3 in which tumor suppressor gene may exist. The LOH on 6q16.3 may be a prognostic index of children with ALL.</p>

Pathophysiological function of HMGB1 as a late-acting mediator of inflammation / 中国病理生理杂志

High mobility group box chromosomal protein (HMGB1), an abundant eukaryotic nonhistone chromosomal protein, is previously known as a nuclear DNA-binding protein that stabilizes the structure and function of chromatin, regulates gene transcription. Recent studies identify that extracellular HMGB1 as a late mediator of endotoxemia and sepsis.HMGB1 is released by activated macrophages,induces the release of other proinflammatory mediators,and mediates lethality when overexpressed. It may also be a key signal for eliciting immune responses to cellular injury and death.Moreover,the late kinetics of HMGB1,in compared with other proinflammatory cytokines such as TNF and IL-1,suggest that targeting HMGB1 may provide a wide and clinically accessible therapeutic window.Three independent strategies to inhibit HMGB1 release and action are now available:anti-HMGB1 antibodies,A box,and ethyl pyruvate. This review covers the general features of HMGB1 and progress in research on its newly role as a cytokine participating in the development of sepsis.