Idiopathic myelofibrosis is a type of chronic myeloproliferative disorders characterized by splenomegaly, a leukoerythroblastic blood picture, teardrop poikilocytosis, in various degrees of bone marrow fibrosis and extramedullary hematopoiesis. In this paper, the biological characters and pathogenesis of idiopathic myelofibrosis such as mutation of tyrosine kinase receptor, mutation of GABA transporter 1, JAK2 mutation and c-MPl mutation, as well as other pathogenesis related with idiopathic myelofibrosis were reviewed.
GABA Plasma Membrane Transport Proteins ; genetics ; Humans ; Janus Kinase 2 ; genetics ; Mutation ; Primary Myelofibrosis ; etiology ; genetics ; Receptor Protein-Tyrosine Kinases ; genetics ; Receptors, Thrombopoietin ; genetics

OBJECTIVE To explore the protective effects and mechanisms of Ginsenoside Rg1 (Rg1) on H2O2-induced hippocampal neurons aging in vitro. METHODS The primary culture hippo-campal neurons(7 d)were randomly placed into six groups:normal control group,H2O2(200 μM)treat-ment group,and H2O2+Rg1(1,5 and 10μM)groups.The neurons were with Rg1(1,5 and 10 μmol·L-1) for 6h. H2O2(200 μmol·L-1) was added to the medium and incubate for 18 h. The Dihydroethidium (DHE) staining was performed for ROS production assessment. The LDH release and Hoechst 33258 were performed to examine the neuronal damage and apoptosis. The immunoblot was used to deter-mine the expression of β-Gal,NOX2,p22phox,p47phox,NLRP-1,ASC and Caspase-1 in hippocampal neurons.The ELISA was performed to detect the levels of IL-1β and IL-18 released in the supernatant in hippocampal neurons.RESULTS Rg1(5 and 10 μmol·L-1)significantly reduced the ROS production, attenuated H2O2-induced neuronal damage and apoptosis (P<0.05, P<0.01). The immunoblot results showed that Rg1(5 and 10 μmol·L-1)treatment significantly decreased the expression of β-Gal,NOX2, p22phox,p47phox,NLRP-1,ASC and Caspase-1 in hippocampal neurons(P<0.05,P<0.01).Additionally, Rg1(5 and 10 μmol·L-1)treatment significantly decreased IL-1β and IL-18 release in the supernatant. CONCLUSION The protective effect of Rg1 in H2O2-induced hippocampal neurons aging may be due to inhibit NOX2-NLRP1 activation.

OBJECTIVETo investigate the antimicrobial resistance of clinical isolates of Stenotrophomonas matophilia (SMA) and the mechanisms of their drug resistance.

METHODSDisc diffusion method (NCCLS) was used to detect the resistant patterns of 88 initial SMA isolates resistant to 12 antibiotics isolated from a local hospital in the past 4 years. PCR was used to detect the 7 aminoglycosides modifying enzymes genes (AME) against amikacin and gentamicin. Metal-beta-lactamases (MBLs) were screened by synergic method, and extended-spectrum beta-lactamases (ESBLs) were detected by double-disk synergy test.

RESULTSThe resistance rates of the SMA isolates were 0%-9.7% to minocycline, 12.5%-22.6% to ticarcillin-clavulanic acid, 12.5%-28.6% to levofloxacin, 18.8%-33.3% to doxycycline, 18.8%-40% to sulfamethoxazole compound, 50%-65.7% to ciprofloxacin, 50%-66.7% to cehazindme, 54.8%-66.7% to amikacin, 75%-100% to gentamicin, 81.3%-100% to piperacillin, 87.5%-100% to aztreonam and 93.5%-100% to imipenem. Aac(3)-I and ant(4')-II were not detected in these strains. The positive rates of the other 5 AME genes of aac(3)-II, ant(2'')-I, aac(6')-I, aac(3)-III, aac(3)-IV were 2.3%, 5.7%, 8%, 10%, and 10%, respectively. SMA strains producing ESBLs were found at the rate of 38.6%; 25% of the strains were MBL-producing, and 13.6% produced both ESBLs and MBLs.

CONCLUSIONMost of the SMAs we isolated are multidrug-resistant through various mechanisms. The choice of antibiotics should be made according to the susceptibility results.

Amikacin ; pharmacology ; Drug Resistance, Multiple, Bacterial ; Gentamicins ; pharmacology ; Humans ; Imipenem ; pharmacology ; Microbial Sensitivity Tests ; Stenotrophomonas maltophilia ; drug effects ; isolation & purification

OBJECTIVETo explore the effects of growth hormone( GH) supplementation on erectile function and expression of nNOS in the intracavernosal nerves in aging rats.

METHODSTwenty male Sprague-Dawley rats aged 18 months were randomly divided into Groups A and B, and ten 2-month-old male Sprague-Dawley rats included in Group C. 1 U/(kg x d) GH was given to Group A, and the same volume of saline to Groups B and C. After 8 weeks of treatment, evaluation was made of the erections induced by apomorphine (APO), maximal intracavernous pressure (ICP) induced by intracavernous papaverine injection and expression of nNOS in the intracavernosal nerves by streptavidin-peroxidase immunohistochemical techniques.

RESULTSAfter 8 weeks of treatment, the erection frequency, maximal ICP and expression of nNOS in the intracavernosal nerves of the rats in Groups A and C were significantly higher than those in Group B (P < 0.05 or P < 0.01).

CONCLUSIONGrowth hormone supplementation can improve the erectile function of aging rats, which may be attributed to the increase in the expression of nNOS in the intracavernosal nerves.

Animals ; Apomorphine ; pharmacology ; Growth Hormone ; pharmacology ; Immunohistochemistry ; Male ; Nitric Oxide Synthase Type I ; biosynthesis ; Papaverine ; pharmacology ; Penile Erection ; drug effects ; Penis ; enzymology ; innervation ; Random Allocation ; Rats ; Rats, Sprague-Dawley

OBJECTIVESThis study try to subclassify breast cancer into different prognostic subgroups according to immunohistochemical algorithm and discuss the relationship between subtypes and biological and clinical behavior and prognosis.

METHODSOne hundred and twenty-eight cases of infiltrative ductal carcinoma were studied using immunohistochemical staining with an antibody panel of ER, PR, HER2 and CK5/6 and subclassified referring to previous reports, and the 9 cases of HER2 positive subtype were tested using FISH.

RESULTSThe expression of ER, PR, HER2, and CK5/6 was detected in 67%, 45%, 27% and 27% cases, respectively. All cases were subclassified into five subgroups, with luminal A (55%), luminal B (20%), HER2 positive (7%), basal-like (10%) and unclassified cases (8%). Nine HER2 positive cases all showed amplification of HER2 gene. It was demonstrated that the luminal A group was associated with the best prognosis but the basal-like group worst by univariate analysis. Multivariate analysis demonstrated that both the clinical stage and immunohistochemical subtypes of tumor were related to overall survival. Menses status were different among these subtypes.

CONCLUSIONAccording to the expression of ER, PR, HER2 and CK5/6, infiltrative ductal carcinoma could be subclassified into five subgroups with different biological features and outcome, having a role in evaluating the prognosis and guiding the clinical treatment.

Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms ; classification ; metabolism ; pathology ; Carcinoma, Basal Cell ; metabolism ; pathology ; Carcinoma, Ductal, Breast ; classification ; metabolism ; pathology ; Female ; Follow-Up Studies ; Humans ; Keratin-5 ; metabolism ; Keratin-6 ; metabolism ; Middle Aged ; Neoplasm Staging ; Prognosis ; Receptor, ErbB-2 ; metabolism ; Receptors, Estrogen ; metabolism ; Receptors, Progesterone ; metabolism ; Survival Rate ; Tumor Burden

OBJECTIVE: The leukemia cells from patients with T-cell acute lymphoblastic leukemia (T-ALL) were inoculated into NCG mice to establish a stable human T-ALL leukemia animal model. METHODS: Leukemia cells from bone marrow of newly diagnosed T-ALL patients were isolated, and the leukemia cells were inoculated into NCG mice via tail vein. The proportion of hCD45 positive cells in peripheral blood of the mice was detected regularly by flow cytometry, and the infiltration of leukemia cells in bone marrow, liver, spleen and other organs of the mice was detected by pathology and immunohistochemistry. After the first generation mice model was successfully established, the spleen cells from the first generation mice were inoculated into the second generation mice, and after the second generation mice model was successfully established, the spleen cells from the second generation mice were further inoculated into the third generation mice, and the growth of leukemia cells in peripheral blood of the mice in each group was monitored by regular flow cytometry to evaluate the stability of this T-ALL leukemia animal model. RESULTS: On the 10th day after inoculation, hCD45⁺ leukemia cells could be successfully detected in the peripheral blood of the first generation mice, and the proportion of these cells was gradually increased. On average, the mice appeared listless 6 or 7 weeks after inoculation, and a large number of T lymphocyte leukemia cells were found in the peripheral blood and bone marrow smear of the mice. The spleen of the mice was obviously enlarged, and immunohistochemical examination showed that hCD3⁺ leukemia cells infiltrated into bone marrow, liver and spleen extensively. The second and third generation mice could stably develop leukemia, and the average survival time was 4-5 weeks. CONCLUSION Inoculating leukemia cells from bone marrow of patients with T-ALL into NCG mice via tail vein can successfully construct a patient-derived tumor xenografts (PDTX) model.
Humans ; Animals ; Mice ; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma ; Heterografts ; Bone Marrow ; Disease Models, Animal ; T-Lymphocytes ; Mice, SCID

OBJECTIVE: To investigate the inflammatory effects of Cinobufotalin on monocytes in resting state and macrophages in activated state and its molecular mechanism. METHODS: THP-1 cells were stimulated with Phorbol 12-myristate 13-acetate to induce differentiation into macrophages. Lipopolysaccharides was added to activate macrophages in order to establish macrophage activation model. Cinobufotalin was added to the inflammatory cell model for 24 h as a treatment. CCK-8 was used to detect cell proliferation, Annexin V /PI double staining flow cytometry was used to detect cell apoptosis, flow cytometry was used to detect macrophage activation, and cytometric bead array was used to detect cytokines. Transcriptome sequencing was used to explore the gene expression profile regulated by Cinobufotalin. Changes in the significantly regulated molecules were verified by real-time quantitative polymerase chain reaction and Western blot. RESULTS: 1∶25 concentration of Cinobufotalin significantly inhibited the proliferation of resting monocytes(P<0.01), and induced apoptosis(P<0.01), especially the activated macrophages(P<0.001, P<0.001). Cinobufotalin significantly inhibited the activation of macrophages, and significantly down-regulated the inflammatory cytokines(IL-6, TNF-α, IL-1β, IL-8) released by activated macrophages(P＜0.001). Its mechanism was achieved by inhibiting TLR4/MYD88/P-IκBa signaling pathway. CONCLUSION Cinobufotalin can inhibit the inflammatory factors produced by the over-activation of macrophages through TLR4/MYD88/P-IκBa pathway, which is expected to be applied to the treatment and research of diseases related to the over-release of inflammatory factors.
Humans ; Toll-Like Receptor 4/metabolism* ; Myeloid Differentiation Factor 88/genetics* ; Macrophages/metabolism* ; Cytokines/metabolism* ; Lipopolysaccharides/pharmacology* ; NF-kappa B