OBJECTIVETo observe the effect of leukemic cells on blood-brain barrier (BBB) in mice with central nervous system leukemia (CNSL) by establishing mice CNSL model and an in vitro BBB model and explore the mechanism of leukemic cell infiltrating central nervous system (CNS).

METHODSAfter splenectomy, cytoxan intraperitoneal injection, and sublethal irradiation, 10 BALB/c nu/nu mice were transplanted intravenously with 1.2 × 10(7) of SHI-1 human monocytic leukemic cells. Mice were monitored for survival and clinical manifestation of nerve palsy. The leukemic cells engrafted were examined by RT-PCR, histopathology and bone marrow (BM) smears. Immunofluorescence analysis with laser scanning fluorescence confocal microscopy was used to determine the expression of fibrinogen and tight-junction protein ZO-1. An in vitro BBB model composed of human brain microvascular endothelial cells (BMVECs) was developed on a Matrigel-based insert. Different leukemic cell lines were seeded onto the upper compartment of transwell insert. After incubated for 24 h with BMVECs, cells that had migrated into the lower compartment were counted and analyzed.

RESULTS(1) Paralysis with or without sight loss was developed in half the mice 30-35 d after innoculated with SHI-1 cells. Leukemic cells infiltrates were observed in BM and in different part of brain tissues including brain parenchyma. The transcriptions of human MLL/AF6 fusion gene were also detected in BM and brain tissues in paralysis mice. The fibrinogen expression and ZO-1 disruption were detected in the infiltrated tissue. (2) After 24 h incubation with leukemic cells, the BMVECs sheets were disrupted and grew singly and ZO-1 expression was down-regulated markedly. SHI-1 cells showed more injurious to BMVECs and higher invasive rate \[(40.33 ± 1.53)% vs (11.83 ± 1.44)%, P < 0.05\] than HL-60 cells did.

CONCLUSIONOne of the mechanisms of leukemic cells infiltrates CNS in CNSL is injure to the BBB.

Animals ; Blood-Brain Barrier ; physiology ; Central Nervous System ; pathology ; Central Nervous System Neoplasms ; pathology ; HL-60 Cells ; Humans ; Leukemia ; pathology ; Mice ; Mice, Inbred BALB C ; Mice, Nude

OBJECTIVETo study the expression ratio of AML1-ETO9a (AE9a) isoform in t(8;21) acute myeloid leukemia (AML) and its clinical significance.

METHODSBone marrow samples from 44 newly diagnosed t(8;21) AML patients co-expressed AE9a and AE were screened by RT-PCR. The alteration of the AE9a expression ratio was monitored during follow-up by using quantitative real-time RT-PCR (qPCR).

RESULTSThe expression level of AE9a was markedly lower than that of AE in these patients. There was a positive correlation between the expression level of AE9a and AE in most of bone marrow samples. The transcript level of both AE9a and AE was decreased in the 44 patients after one course of standard chemotherapy, but the percentage of AE9a expression level was increased in comparison with that before treatment (P < 0.05). After one course of standard chemotherapy treatment, the percentage of AE9a in incomplete remission (ICR) patients was significantly higher than that in CR patients (P < 0.05). Relapsed patients had a higher AE9a ratio than the unrelapsed patients (P < 0.05). During the remission, the percentage of AE9a in 11/17 relapsed patients obviously elevated even while the expression of AE fusion gene at low level.

CONCLUSIONSAE9a and AE co-expressed in most of AML patients with t(8;21) translocation. The expression level of AE9a was lower than that of AE, and there is a positive correlation between the expression level of these two isoforms. The sensitivity of AE9a gene to the standard chemotherapy is less than that of the AE fusion gene. Monitoring the AE9a to AE ratio during the CR can predict the early relapse of the disease compared to monitoring the AE alone.

Adolescent ; Adult ; Child ; Chromosomes, Human, Pair 21 ; Chromosomes, Human, Pair 8 ; Core Binding Factor Alpha 2 Subunit ; genetics ; Female ; Gene Expression ; Humans ; Leukemia, Myeloid, Acute ; genetics ; pathology ; Male ; Middle Aged ; Oncogene Proteins, Fusion ; genetics ; Protein Isoforms ; genetics ; RUNX1 Translocation Partner 1 Protein ; Translocation, Genetic ; Young Adult

Objective To study the relationship between myofibril fragmentation index (MFI) of human skeletal muscle and postmortem interval (PMI). Methods The protein concentrations of human right bi-ceps brachii muscle and right quadriceps femoris muscle were obtained at different PMI, and detected at room temperature by biuret method. The MFI of skeletal muscle at 540 nm was measured by ultraviolet spectrophotometer. Regression analysis was performed with time of death as independent variable (x) and MFI as dependent variable (y). Results In early PMI, the MFI of human skeletal muscle increased obviously according to the prolongation of PMI, and peaking by 12 h and then tended to steady. Within 12 h after death, the regression equations of right biceps brachii muscle and right quadriceps femoris muscle were y=32.660+3.227 x(r=0.9879) and y=32.380+3.495 x(r=0.9839), respectively. Conclusion There's high correlation between MFI and PMI. Combining with forensic practice, MFI can be used for the estimation of early PMI (especially in 12 h).

OBJECTIVETo explore the feasibility of magnetic resonance cell imaging technology by using polyethylene imine (PEI)-coated magnetic nanoparticles of Fe₄O₄ (PEI-Fe₄O₄-MNPs) to track cell biology behavior.

METHODSEndocytic PEI-Fe₄O₄-MNPs in SHI-1 cells were observed by transmission electron microscopy (TEM) . Iron contents of nano-labeled cells were analyzed by inductively coupled plasma-atomic emission spectroscopy (ICP-AES) and Prussian blue staining. The proliferation ability of labeled cells was detected by cell counting kit-8 (CCK-8) assay; the differentiation and colony-forming abilities were also observed. SHI-1 cells without endocytosing PEI-Fe₄O₄-MNPs were used as control.

RESULTSOur data showed that PEI-Fe₄O₄-MNPs could label SHI-1 cells. The labeling efficiency depended on the nanoparticles' concentration and the duration of cells treating. Inhibition rates of SHI-1cells labeled by 60-100 μg Fe/ml PEI-Fe₄O₄-MNPs were much higher than of 5-50 μg Fe/ml ones following treating by 5-100 μg Fe/ml PEI-Fe₄O₄-MNPs for 48 hrs. The expressions of CD11b and CD14 were (78.4±18.5)% and (18.7±2.9)% in control vs (83.3±14.2)% and (20.4±2.1)% in cells fractions treated by 30 μg Fe/ml PEI-Fe₄O₄-MNPs. Clony-forming rates of SHI-1 cells labeled by 0, 20 , 50 μg Fe/ml PEI-Fe₄O₄-MNPs were (25.20±7.22)%, (25.93±13.15)%, (23.37±9.33)%, respectively. Differentiation and colony-forming potentials of labeled cells were similar with control in the certain range of PEI-Fe₄O₄-MNPs concentration.

CONCLUSIONSHI-1 cells were efficiently labeled by PEI-Fe₄O₄-MNPs with well biocompatibilities in proper range of concentration, the latter could be coupled with magnetic resonance imaging (MRI) to track cells in vivo.

Cell Line, Tumor ; Coated Materials, Biocompatible ; chemistry ; Ferric Compounds ; chemistry ; Humans ; Magnetic Resonance Imaging ; Magnetics ; Microscopy, Electron, Transmission ; Nanoparticles ; chemistry ; Polyethyleneimine ; chemistry

BACKGROUNDDiabetes management could be improved by diabetes education, through influencing attitudes towards diabetes, knowledge and behaviors of patients. The purpose of this study was to characterize the impact of diabetes education on glycemic control, and to assess the attitude, knowledge and self-care behavior in patients with type 2 diabetes in China.

METHODSThis questionnaire-based survey was conducted in 50 medical centers across China from April to July of 2010. The patients with type 2 diabetes were eligible for the study. The information of glycemic control and diabetes education was collected. The diabetes attitude scale-3 formulae, a questionnaire of diabetes knowledge and Summary of Diabetes Self-care Activities scale were used to assess attitude, knowledge and the self-care of patients, respectively.

RESULTSAmong the 5961 eligible respondents (3233 males; mean age (59.50 ± 12.48) years; mean hemoglobin A1c (HbA1c) (8.27 ± 2.23)%), most patients (79.8%) considered themselves educated on diabetes. Compared with patients without diabetes education, their educated counterparts showed significant lower value of HbA1c, after controlling for age, gender, body mass index and duration of diabetes (P < 0.01). The patients who received diabetes education also performed significant higher scores on attitude, knowledge and self-care than their uneducated counterparts. Patients with lower income or education level tended to have higher glucose levels, and showed lower percentage of patients received diabetic education.

CONCLUSIONSChinese patients with diabetes education achieved better glycemic control than un-educated patients. Our study indicates effort is required to provide professional education to patients, with emphasis on lower income and lower education level populations.

Aged ; Blood Glucose ; metabolism ; China ; Cross-Sectional Studies ; Data Collection ; Diabetes Mellitus, Type 2 ; blood ; Female ; Health Knowledge, Attitudes, Practice ; Humans ; Male ; Middle Aged ; Self Care ; Surveys and Questionnaires

Objective: To investigate the clinical significance of tumor associated macrophages (TAM) in multiple myeloma (MM) and the relationship with angiogenesis and immunosuppression. Methods: Seventy cases of MM patients diagnosed from August 2015 to June 2017 were enrolled in the study as experimental group, 20 cases of benign hematological diseases (13 with iron deficiency anemia and 7 with megaloblastic anemia) patients as control group. Immunohistochemical method was used to detect the expression of CD163, CD34 and VEGF in bone marrow samples, and flow cytometry was used to detect the proportion of regulatory T cell (Treg cells), ELISA was used to detect the level of IL-10, and the clinical features were analyzed. Results: ①Among the 70 patients, there were 31 males and 39 females with a median age of 65 (50~78) years old. TAM infiltration density, microvascular density (MVD), VEGF expression level, Treg ratio and IL-10 level in bone marrow samples of 70 MM patients were significantly higher than those of benign hematological diseases (P<0.05). ②In the MM group, the above indexes of the patients with disease stabilized (15 cases) were lower than those of the newly diagnosed group (35 cases) and the relapse refractory group (20 cases) (P<0.05), those of relapse refractory group were higher than those of newly diagnosed group (P>0.05). ③Of the 35 newly diagnosed MM patients, 27 completed 4 courses of treatment. In the effective group (15 cases), the TAM infiltration density after treatment was significantly lower than that before treatment, the difference was statistically significant[(20.20±7.66) vs (28.87±11.97), t=2.362, P=0.025]; while in the ineffective group of 12 cases, the difference of the TAM infiltration density before and after treatment was not statistically significant[(42.00±13.76) vs (48.25±13.59), t=1.119, P=0.275]. ④TAM infiltration density in the effective group after bortezomib treatment (21 cases) were lower than those in the non-bortezomib treatment group (18 cases)[(16.52 ±4.26) vs (19.27 ±5.82), t=1.662, P=0.170]. ⑤The TAM infiltration density in MM patients was positively correlated with MVD, VEGF expression level, Treg cell ratio and IL-10 level (P<0.001). Conclusion: The infiltration of TAM in the microenvironment of MM, which may promoting angiogenesis and inhibiting immune response, is related to the occurrence, development, therapeutic effect and drug resistance of MM.
Aged ; Female ; Humans ; Macrophages ; Male ; Middle Aged ; Multiple Myeloma ; Neoplasm Recurrence, Local ; Neovascularization, Pathologic

OBJECTIVETo find an approach for trans-oral endoscopic thyroidectomy (TOET) and cervical lymphadenectomy using conventional endoscopic surgical instruments on frozen fresh cadavers.

METHODSSix frozen fresh cadavers were used in three groups of trans-oral trocar installation experiments: oral vestibule installation, sublingual region installation, and combined bi-vestibular and sublingual installation. TOET (with pretrachealis method to thyroid fixation removal) and cervical lymphadenectomy were performed experiments on another 6 frozen fresh cadavers using the best access approach found in the aforementioned experiments.

RESULTSIn oral vestibule trocar installations, the trocars caused large lacerated wound and damaged air tightness. In sublingual installations, only one trocar could be installed in the sublingual area because the space in sublingual area was limited. In combined bi-vestibular and sublingual installations, no gland, vessel or nerve was damaged. Combined bi-vestibular and sublingual access were selected as the surgical approach on the basic of analysis the merits of each approach. TOET and cervical lymphadenectomy in area III, IV, VI, VII were performed without making any accessory damage through combined bi-vestibular and sublingual access approach.

CONCLUSIONSTOET is feasible. Combined bi-vestibular and sublingual approach is available for TOET. Part of the cervical lymph nodes could be resected. Pretrachealis approach to thyroid fixation removal can still be used.

Adult ; Cadaver ; Endoscopy ; Humans ; Lymph Node Excision ; methods ; Neck ; Thyroidectomy ; methods

OBJECTIVETo evaluate the effects of nasal mometasone furoate on moderate to severe allergic rhinitis.

METHODSPatients with moderate to severe allergic rhinitis were enrolled and received mometasone furoate nasal spray 200 microg once daily for four weeks. Four hundreds and sixty-three patients completed the study. We weekly interviewed the patients to evaluate the symptoms, and the affection of disease on night sleep and daily life. Mini Rhinoconjunctivitis Quality of Life Questionnaire (Mini-RQLQ) and Nocturnal Rhinoconjunctivitis Quality of Life Questionnaire (NRQLQ) were used to evaluate the quality of life.

RESULTSThe individual and total symptomatic scores of week 1, week 2 and week 4 decreased compared with baseline. The scores of Mini-RQLQ and NRQLQ of week 1, week 2 and week 4 decreased compared with baseline too. The scores of the next visit were significantly lower than those of the previous visit (P < 0.01).

CONCLUSIONSA four-week administration of mometasone furoate nasal spray can effectively treat allergic rhinitis.

Administration, Intranasal ; Adolescent ; Adult ; Aged ; Anti-Allergic Agents ; administration & dosage ; therapeutic use ; Child ; Female ; Humans ; Male ; Middle Aged ; Mometasone Furoate ; Pregnadienediols ; administration & dosage ; therapeutic use ; Quality of Life ; Rhinitis, Allergic, Perennial ; drug therapy ; Surveys and Questionnaires ; Young Adult

BACKGROUNDAtherosclerosis is the primary cause of cardiovascular disease, carotid artery disease, and peripheral vascular disease. However, it is hard to obtain human arterial tissue at different stages of atherosclerosis for a systematic study. The ApoE-deficient (ApoE(-/-)) mice predictably develop spontaneous atherosclerotic plaques with numerous features similar to the human lesions and contain nearly the entire spectrum of lesions observed during atherogenesis in humans. MicroRNA expression profiles at different stages of atherosclerosis in ApoE-deficient mice were screened to find out the differentially expressed microRNAs.

METHODSApoE-deficient mice were euthanized at 4, 8, and 20 weeks of age and divided into three groups according to the three time points, including groups A4 (fed a Western-type diet for 0 week), A8 (fed a Western-type diet for 4 weeks), and A20 (fed a Western-type diet for 16 weeks). Atherosclerotic lesions were analyzed. Fifteen aortas were collected and combined into three pools (five aortas in one pool) in each group. MicroRNA microarray analysis was replicated thrice in each group. The threshold of fold change ≥ 2.0 was used to screen up or down-regulated microRNAs. Differentially expressed microRNAs were subsequently verified with quantitative real-time polymerase chain reaction. Those increasingly up or down-regulated microRNAs during the progression of atherosclerosis were selected.

RESULTSAtherosclerotic lesions first appeared in the aortic arch in group A8. Severe atherosclerotic lesions were observed in group A20. In group A8, seven MicroRNAs were up-regulated while two were down-regulated. In group A20, 15 microRNAs were up-regulated while two were down-regulated. miR-34a-5p and miR-497-5p were increasingly up-regulated, while miR-434-3p was progressively down-regulated when atherosclerosis progressed.

CONCLUSIONSIn this study, we described that microRNAs are differentially expressed at different stages of atherosclerosis in ApoE-deficient mice. Those increasingly up or down-regulated microRNAs during the progression of atherosclerosis may play an important role in the pathogenesis of atherosclerosis and provide us opportunities for investigating atherosclerosis from early to advanced stages.

Animals ; Apolipoproteins E ; deficiency ; genetics ; Atherosclerosis ; genetics ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; MicroRNAs ; genetics ; Real-Time Polymerase Chain Reaction

Objective To describe the effects of China diabetes educator training and explore the influencing factors.Methods Totally 314 diabetes educators who graduated from Johnson & Johnson Diabetes Institute(JJDI) from 2007 to 2014 were recruited and investigated via self-designed evaluation form.Results The total score was 76.64±22.24.The top three items with highest scores were performing nurses training (93.36±62.81),form of health education (84.27±23.09) and working responsibility and procedure of diabetes educator (82.07±32.43).The items scored lower than 60 were regular follow-up system(56.16±31.74),publishing health education papers(38.47±47.75) and conducting related researches (26.11±44.00).Multiple linear regression analysis showed that educators who had longer time of working in diabetes department(t=3.515,P=0.001) and whose post were educators(t=3.404,P=0.001) and who were not first line practitioners (t=-2.589,P=0.001) had higher scores.Conclusion The educators' main work in China is focusing on regular health education.Follow-up management and research renovation capacity should be enhanced in the future for educators.