OBJECTIVETo identify genetic alterations in diffuse large B-cell lymphoma (DLBCL) and to analyse the relationship between the genetic aberrations and the clinical characteristics.

METHODSUsing comparative genomic hybridization (CGH) to investigate the genomic changes in 24 cases of DLBCL and to analyse the relationship between these aberrations and clinical parameters including Ann arbor stage, systemic symptoms, chemotherapy efficacy and survival.

RESULTSAberrations were detected in 62.5% patients of 24 cases; the most common chromosomal alterations included loss of 6q15-21 as well as gain of 18q11-ter, of which the incidences were 20.8% and 16.7%, respectively; with comparing clinical parameters between patients with normal CGH and abnormal CGH, we found that patients with abnormal CGH suffered more from stage III-IV and had higher incidence of systemic symptoms, poor chemotherapy efficacy and poor survival (P<0.05), but there was no difference observed in the incidence of extranodal involvement between two groups.

CONCLUSIONThe gains and/or losses of genomic DNA from DLBCL patients are the common molecular cytogenetic aberrations; loss of 6q15-21 and gain of 18q11-ter are nonrandom event to DLBCL patients; abnormal CGH is a clinical parameter reflecting malignant progressive course and poor survival to DLBCL patients.

Chromosome Aberrations ; Female ; Humans ; Karyotyping ; Lymphoma, B-Cell ; genetics ; pathology ; physiopathology ; Lymphoma, Large B-Cell, Diffuse ; genetics ; pathology ; physiopathology ; Male ; Nucleic Acid Hybridization ; Statistics as Topic

To investigate the potential role and the mechanism of PLZF-RARalpha/RARalpha-PLZF double fusion gene in the pathogenesis of acute promyelocytic leukemia (APL) in vivo at systematic biological level, PLZF-RARalpha/RARalpha-PLZF double transgenic mouse model was established by intercross; the integration and expression of fusion genes were analyzed by PCR and RT-PCR; the disease phenotype was detected by morphological and pathological examination of peripheral blood and bone marrow cells, as well as flow cytometry assays; the effects of ATRA with or without tricostatin A on bone marrow blast cells from PLZF-RARalpha/RARalpha-PLZF double TM were observed. The results showed that leukemia occurred in 5 PLZF-RARalpha/RARalpha-PLZF double TM 7, 7, 9, 11 and 11 months respectively, out of them two (40%) with classic APL features, the others (60%) with chronic myeloid leukemia through an observation period of 18 months. The leukemia occurrence of PLZF-RARalpha/RARalpha-PLZF TM was about 10%, which was similar to PLZF-RARalpha TM as that reported before. The latency was over 6 months, not earlier than PLZF-RARalpha TM only. No morphologic changes of PLZF-RARalpha/RARalpha-PLZF double TM blast cells to ATRA were observed, but increased cytoplasmic-nuclear ratio and nuclear condensation in bone marrow blast cells were found in combination of ATRA with tricostatin A. It is concluded that PLZF-RARalpha/RARalpha-PLZF double fusion gene transgenic mice have heterogeneity of pathogenesis. HDAC inhibitors such as trichostatin A, in combination with ATRA, induce differentiation of the blast/promyelocytic cells from PLZF-RARa/RARa-PLZF double TM, but not ATRA alone.
Animals ; Antigens, CD34 ; blood ; Bone Marrow Cells ; drug effects ; immunology ; pathology ; Cell Differentiation ; drug effects ; Chorionic Gonadotropin ; genetics ; Disease Models, Animal ; Female ; Flow Cytometry ; Humans ; Hydroxamic Acids ; pharmacology ; Leukemia, Promyelocytic, Acute ; blood ; genetics ; pathology ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Inbred CBA ; Mice, Transgenic ; Oncogene Proteins, Fusion ; genetics ; Pedigree ; Receptors, Chemokine ; blood ; Tretinoin ; pharmacology

Diagnosis, Differential ; Female ; Humans ; Middle Aged ; Pancreatic Neoplasms ; diagnosis ; Solitary Fibrous Tumors ; diagnosis

OBJECTIVETo better understand the mechanisms of the fetal hematopoiesis turn over from primitive to definitive hematopoiesis through the expression level of c-kit(+) and sca-1(+), and major characters of gene expression profile of these cells.

METHODSc-kit and sca-1 expression level were monitored with fluorescence activated cell sorting (FACS) of the mononuclear cells from mouse yolk sac and fetal liver, while gene expression profile was carried out with EST sequencing strategy.

RESULTSThe Sca-1(+) cells were increased while the c-kit(+) cells decreased with the embryonic development. Through profiling the functionally identified known genes, most of the highly expressed were globin genes, especially of embryonic types.

CONCLUSIONThe erythropoiesis played a key role in early fetal hematopoiesis in mammalian.

Animals ; Antigens, Ly ; genetics ; metabolism ; Cell Differentiation ; genetics ; Flow Cytometry ; Gene Expression Profiling ; Gene Expression Regulation, Developmental ; Liver ; cytology ; embryology ; metabolism ; Membrane Proteins ; genetics ; metabolism ; Mice ; Mice, Inbred C57BL ; Proto-Oncogene Proteins c-kit ; genetics ; metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Time Factors ; Yolk Sac ; cytology ; embryology ; metabolism

The study was aimed to investigate the BCL-XL expression and mutation, and its clinical significance in non-Hodgkin's lymphoma. Lymphoma cells were selectively isolated by laser microdissection. BCL-XL expression from lymphoma tissue and microdissected lymphoma cells was measured by using real-time quantitative reverse transcription-polymerase chain reaction. BCL-XL mutation was analyzed by using direct sequencing of PCR products. The results showed that compared to 15 patients with reactive hyperplasia, BCL-XL was overexpressed in follicular lymphoma (n = 30), both in lymphoma tissue (P = 0.0064) and in microdissected lymphoma cells (P < 0.0001). No significant rise of BCL-XL expression was observed in patients with T-cell lymphoma (n = 24) and diffuse large B cell lymphoma (n = 24). In follicular lymphoma, high BCL-XL level was associated with multiple extranodal involvement (P = 0.0004), elevated lactate dehydrogenase level (P = 0.0019), high-risk international prognostic index (P = 0.0013) and a short overall survival time (P = 0.0451). Mutation analysis revealed one synonymous mutation (Codon 109 ACA-->ACC) in one case of follicular lymphoma patient. It is concluded that BCL-XL expression is closely correlated with progress of follicular lymphoma and prognosis of patients with follicular lymphoma. The value of BCL-XL expression as a prognostic marker in follicular lymphoma should be considered.
Base Sequence ; Humans ; Lymphoma, Follicular ; genetics ; pathology ; Lymphoma, Non-Hodgkin ; genetics ; pathology ; Molecular Sequence Data ; Point Mutation ; bcl-X Protein ; biosynthesis ; genetics

OBJECTIVETo study the biological function of fusion gene HRX-EEN and its role in leukemogenesis, and to provide an ideal animal model for anti-leukemia drug screening.

METHODSHRX-EEN fusion gene was constructed by use of three different DNA fragments, and it was inserted into hCG transgenic vector. G(0) transgenic mice were obtained by microinjection of the recombined DNA into the pronucleus of zygotes, followed by implantation of the injected zygotes into pseudopregnant mice. The integration of the transgene was tested by PCR and its expression by reverse transcription-polymerase chain reaction (RT-PCR).

RESULTSThe sequence of recombined HRX-EEN gene was confirmed by sequencing. PCR testing revealed a total of 7 G(0) transgenic mice, these mice were then mated with C57 wild type mice. Except mouse No. 35 that died, the others all had their F1 offsprings. From these 6 lines of transgenic mice, HRX-EEN gene was found to be stably expressed in 3 lines by RT-PCR. Up to now, all transgenic mice expressing the fusion gene have no obvious abnormal phenotypes.

CONCLUSIONA transgenic mice model in which the HRX-EEN fusion gene can be stably expressed has been established.

Animals ; DNA-Binding Proteins ; genetics ; Histone-Lysine N-Methyltransferase ; Intracellular Signaling Peptides and Proteins ; Mice ; Mice, Transgenic ; Myeloid-Lymphoid Leukemia Protein ; Polymerase Chain Reaction ; Proteins ; genetics ; Proto-Oncogenes ; Recombinant Fusion Proteins ; genetics ; Transcription Factors

OBJECTIVEIn order to investigate the leukemogenic potential of NUP98-PMX1 fusion gene in vivo.

METHODSNUP98-PMX1 transgenic mice were generated, in which the fusion gene was driven by hCG promoter and expressed in myeloid cells at early stage of differentiation. Molecular cloning technology was used to construct NUP98-PMX1 transgenic plasmid. The genotype and phenotype of the NUP98-PMX1 transgenic mice were analyzed by PCR, RT-PCR, peripheral blood count (PBC), bone marrow (BM) cells morphology and pathological examination.

RESULTSNIH3T3 cells transfected with NUP98-PMX1 fusion gene grew faster, formed colonies in soft agar, and developed tumors in 10 inoculated nude mice. Among 8 disordered NUP98-PMX1 transgenic mice, 4 developed myeloid leukemia-like phenotype, including 3 resembling human chronic myeloid leukemia.

CONCLUSIONNUP98-PMX1 has oncogenic activity and plays a crucial role in leukemogenesis.

Animals ; Bone Marrow Cells ; metabolism ; pathology ; Disease Models, Animal ; Female ; Flow Cytometry ; Gene Expression Regulation, Leukemic ; Green Fluorescent Proteins ; genetics ; metabolism ; Humans ; Leukemia, Myeloid ; genetics ; pathology ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Inbred Strains ; Mice, Nude ; Mice, Transgenic ; NIH 3T3 Cells ; Nuclear Pore Complex Proteins ; genetics ; metabolism ; Oncogene Proteins, Fusion ; genetics ; metabolism ; Phenotype ; Plasmids ; Recombinant Fusion Proteins ; genetics ; metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Transfection

The incidence of spinal cord injury is increasing year by year, and more and more attentions have been paid. Growth factors can promote the regeneration of nerve fibers and synapses, and they also play an important role in the treatment of spinal cord injury and the recovery of neurological function. The growth factor itself has a short half-life, so it is necessary to use growth factor gene vectors to transfect stem cells and nanoparticles to deliver growth factors or biocompatible scaffolds to support growth factors to treat spinal cord injuries. With the development of the research on growth factors, the application of single growth factor is difficult to meet the need of treatment to spinal cord injury. To explore the synergistic effect of various growth factors in order to achieve a better therapeutic effect is a promising research direction in the future. The purpose of this review is to summarize the therapeutic effects of growth factors on spinal cord injury including brain-derived neurotrophic factor, neurotrophic factor 3, nerve growth factor, basic fibroblast growth factor and synergy therapy of growth factors.

Sepsis， a common critical disease in the intensive care unit（ICU）， features high morbidity and mortality. At present， it is mainly tackled with western medicine， which may trigger a series of problems like antibiotic resistance， adverse hormonal reactions， and high cost after a long-term use. Therefore， exploring new efficient， safe， and cheap drugs and treatment modes has become the focus of our research at this stage. By virtue of unique advantages including "the concept of holism and individualized treatment based on syndrome differentiation"， Chinese medicine has accumulated quite rich experience in the prevention and treatment of sepsis. In recent years， research on the regulation of Chinese medicine on nuclear transcription factor-κB（NF-κB） signaling pathway in sepsis has kept emerging. On this basis， this paper reviewed the etiology and pathogenesis of sepsis， syndrome differentiation and treatment， NF-κB signaling pathway， and its intervention with Chinese medicine. It has been found that some single Chinese herbs and their extracts， Chinese herbal compounds， and Chinese herbal injections effectively inhibit the expression of such inflammatory factors as NF-κB-mediated tumor necrosis factor-α（TNF-α）， interleukin-1（IL-1）， and IL-6 as well as the related proteins， reduce the systemic inflammatory response and organ injury， and improve the prognosis by regulating the activation of NF-κB signaling pathway and the immune function of macrophages. However， due to the limitations of objective conditions， some studies also have the problems of fuzzy pro-inflammatory anti-inflammatory balance mechanism， unclear pharmacokinetics and low drug safety evaluation， which need to be further studied and explored in order to provide a new theoretical basis and diagnosis and treatment thinking for the treatment of sepsis with traditional Chinese medicine.

OBJECTIVE: To investigate the current status of antibiotic use for very and extremely low birth weight (VLBW/ELBW) infants in neonatal intensive care units (NICUs) of Hunan Province. METHODS: The use of antibiotics was investigated in multiple level 3 NICUs of Hunan Province for VLBW and ELBW infants born between January, 2017 and December, 2017. RESULTS: The clinical data of 1 442 VLBW/ELBW infants were collected from 24 NICUs in 2017. The median antibiotic use duration was 17 days (range: 0-86 days), accounting for 53.0% of the total length of hospital stay. The highest duration of antibiotic use was up to 91.4% of the total length of hospital stay, with the lowest at 14.6%. In 16 out of 24 NICUs, the antibiotic use duration was accounted for more than 50.0% of the hospitalization days. There were 113 cases with positive bacterial culture grown in blood or cerebrospinal fluid, making the positive rate of overall bacterial culture as 7.84%. The positive rate of bacterial culture in different NICUs was significantly different from 0% to 14.9%. The common isolated bacterial pathogens Klebsiella pneumoniae was 29 cases (25.7%); Escherichia coli 12 cases (10.6%); Staphylococcus aureus 3 cases (2.7%). The most commonly used antibiotics were third-generation of cephalosporins, accounting for 41.00% of the total antibiotics, followed by penicillins, accounting for 32.10%, and followed by carbapenems, accounting for 13.15%. The proportion of antibiotic use time was negatively correlated with birth weight Z-score and the change in weight Z-score between birth and hospital discharge (r=-0.095, -0.151 respectively, P<0.01), positively correlated with death/withdrawal of care (r=0.196, P<0.01). CONCLUSIONS Antibiotics used for VLBW/ELBW infants in NICUs of Hunan Province are obviously prolonged in many NICUs. The proportion of routine use of third-generation of cephalosporins and carbapenems antibiotics is high among the NICUs.
Anti-Bacterial Agents ; Birth Weight ; Humans ; Infant ; Infant, Extremely Low Birth Weight ; Infant, Newborn ; Intensive Care Units, Neonatal ; Surveys and Questionnaires