A large number of documents will be generated in the process of new drug research,including lots of references.These data accumulate into institutional repository.Up to now,the management of document knowledge base in the process of new drug research has not yet been published.The paper uses the reference management software,combined with the document knowledge management system,to analyze and research the management model and method for establishing institutional repository.

Objective To deepen the understanding of chronic eosinophilic leukemia (CEL).Methods The course of diagnosis and treatment in a case of FIP1L1/PDGFRα fusion gene negative CEL was reported. Flow cytometry was used to analyze the immunophenotype of the cells in peripheral blood and pleural fluid. Karyotype was analyzed with G-banding. The expression of FIP1L1/PDGFRα fusion gene was detected by RT-PCR technique. Routine pathological examination of the tissues from bone marrow, lung and spleen were performed. Result A sixteen-year-old girl had severe anemia, fever, splenomegaly,thrombocytopenia and dominant hypereosinophilia lasting for 22 months. Trephine biopsy showed a hypercellular marrow with eosinophilic proliferation and moderate reticular fibrosis. Eosinophilic infiltration was found in lung and spleen and embolism was also found in spleen. She had a clonal chromosomal abnormality t(5;12)(q31;p13). The expression of FIP1L1/PDGFRα was negative. An abnormal clone of T cells expressing CD3-,CD4-,CD8- was found in peripheral blood and pleural fluid, in which the cional T cell accounted for 5.43% and 1.66% of the total lymphocytes respectively. The patient was refractory to treatment with hydroxyurea, prednisone and interferon alpha. She had poor response to a combination of therapy with low dose cytosine arabinoside, mitoxantrone, vincristine, cyclophosphamide, methotrexate and prednisone. She did not respond to imatinib and died of multiple organ failure. Conclusion The present case fulfilled the WHO diagnostic criteria of FIP1L1/PDGFRα(-) CEL which did not respond to routine treatment and imatinib. Allogenic stem cell transplantation should be considered as early as possible in this case. It is noteworthy that clonal CD3-,CD4-,CD8- T-cell abnormality is related to the pathogenesis of CEL.

Objective To investigate the effect of mitogen-activated protein kinases (MAPKs) activation on the heat stressinduced apoptosis of pulmonary microvascular endothelial cells (PMVECs).Methods A mouse model of severe heat stroke was made and TUNEL and immunohistochemistry were employed to detect lung tissue damage.MACS separation was used for isolation of neonatal PMVECs,and TUNEL was utilized to detect the apoptosis of PMVECs.Western blotting was used for determining the MAPKs activation during heat stress recovery (0,2,6h).The monolayer permeability of endothelial cells was detected in terms of transmembrane resistance (TEER) and horseradish peroxidase (HRP).Cells were pretreated with MAPKs activation inhibitors to examine the effect of heat stress on the monolayer cell permeability and apoptosis.Results In mice with severe heat stroke,extensive apoptosis of PMVECs was found in their pulmonary tissues.TUNEL revealed that the number of apoptotic cells increased over time during heat stress recovery period and heat stress could activate MAPKs in PMVECs.Compared with heat stress group,in the cells pretreated with p38 or ERK activation inhibitor PD98059 and SB203580,the monolayer permeability and apoptosis increased while in cells pretreated withJNK inhibitor SP600125,the cellular permeability and apoptosis decreased.Conclusion In mice with severe heat stoke,PMVECs might experience apoptosis and p38 and ERK could inhibit apoptosis while JNK could promote apoptosis.

OBJECTIVETo compare therapeutic effects of local injection with autoallergic platelet rich plasma (PRP) or autoallergic whole blood (AWB) for the treatment of chronic tennis elbow.

METHODSFrom January 2011 to January 2014, 40 patients with chronic tennis elbow were divided into 2 groups, 20 cases in each group: PRP group and AWB group. There were 20 patients in PRP group treated with local injection of autoallergic platelet rich plasma, including 5 males and 15 females, with an average age of (47.50 ± 9.86) years old; and the average course of disease was (4.67 ± 3.27) months. Among the 20 patients in AWB group treated with local injection of autoallergic whole blood, 3 patients were male and 17 patients were female, with an average age of (46.50 ± 9.96) years old;and the average course of disease was (4.53 ± 2.27) months. The elbow joint was fixed with elastic stockings after injection. All the patients were guided to do strengthening and extension exercises during the follow-up period. Visual analog scale (VAS), Mayo scores for elbow and pressure pain threshold (PPT) were used to evaluate clinical effects after injection immediately and 4,8 weeks after treatment. Results:All the patients were followed up,there were no infections and swelling occurred. The VAS, Mayo and PPT scores of patients in PRP group were improved from pre-therapy 7.22 ± 1.32, 56.71 ± 10.90 and 17.47 ± 4.62 to 2.73 ± 1.00, 91.59 ± 6.95 and 21.35 ± 4.80 respectively 8 weeks after treatment. The VAS, Mayo and PPT scores of patients in AWB group were improved from pre-therapy 7.16 ±1.27, 54.72 ± 8.36 and 17.06 ± 4.83 to 3.81 ± 1.36, 82.06 ± 7.89 and 20.12 ± 4.97 respectively 8 weeks after treatment. All the pain and functional variables including VAS, PPT, and Mayo scores were improved significantly in both groups 4 weeks after injection. On the 4th week after injection, there was no statistically significant difference in PPT between two groups; while the VAS and Mayo score of AWB group were lower than those of PRP group. On the 8th week after injection, the VAS of AWB group was higher than that of PRP group; but the Mayo and PPT scores of AWB group were lower than those of PRP group.

CONCLUSIONPRP and AWB injections are both effective to treat chronic lateral epicondylitis. Compared with AWB injection, PRP injection may be more effective in releasing pain and improving function for a longer time.

Adult ; Blood Transfusion ; Case-Control Studies ; Female ; Humans ; Male ; Middle Aged ; Pain Threshold ; Platelet-Rich Plasma ; Tennis Elbow ; therapy ; Visual Analog Scale

The aim of this paper is to compare the cytotoxicity and cellular uptake efficiency of three kinds of poly(b-benzyl-L-amino) block-poly(ethylene glycol) nanoparticles (PXA-PEG-NPs) using Calu-3 cells, and select one as a nasal drug delivery vector for curcumin (Cur). Poly(gamma-benzyl-L-glutamate) block-poly(ethylene glycol) nanoparticles (PBLG-PEG-NPs), poly(gamma-benzyl-L-lysine) block-poly(ethyleneglycol) nanoparticles (PZLL-PEG-NPs) and poly(gamma-benzyl-L-aspartate) block-poly(ethylene glycol) nanoparticles (PBLA-PEG-NPs) were prepared by emulsion-solvent evaporation method. MTT assays were used to evaluate the cytotoxicity of PXA-PEG-NPs against Calu-3 cells. The cellular uptake of nanoparticles was visualized by an inverted fluorescence microscope and quantified by a flow cytometer. The results indicated that even at high concentration of 2 mg x mL(-1) the three nanoparticles had no cytotoxicity on Calu-3 cells. Compared to the curcumin solution, the three curcumin-loaded PXA-PEG-NPs showed significantly higher cellular uptake efficiency on Calu-3 cells (at equal concentration of curcumin with 5 microg x mL(-1) Cur solution), PBLG-PEG-NPs group was the highest. The cellular uptake increased with incubation time, and has positive correlation with nanoparticle concentration. In brief, PXA-PEG-NPs are conducive to delivery Cur into cells, and PBLG-PEG-NPs might be provided as a good nasal drug delivery carrier.
Adenocarcinoma ; metabolism ; pathology ; Administration, Intranasal ; Anti-Inflammatory Agents, Non-Steroidal ; administration & dosage ; metabolism ; Aspartic Acid ; chemistry ; toxicity ; Cell Line, Tumor ; Cell Survival ; drug effects ; Curcumin ; administration & dosage ; metabolism ; Drug Carriers ; Ethylene Glycol ; chemistry ; toxicity ; Humans ; Lung Neoplasms ; metabolism ; pathology ; Lysine ; chemistry ; toxicity ; Nanoparticles ; Particle Size ; Polyethylene Glycols ; chemistry ; toxicity ; Polyglutamic Acid ; analogs & derivatives ; chemistry ; toxicity

OBJECTIVETo study the curative effects of pirfenidone (PF) on pulmonary fibrosis induced by paraquat (PQ) in mice and to provide the theoretical basis for clinical treatment.

METHODSNinety adult healthy male ICR mice were randomly divided into six groups: control group, PQ group, 2 mg/kg Dexamethasone group, 25 mg/kg PF group, 50 mg/kg PF group and 100 mg/kg PF group, there were 15 mice in each group. The corresponding volume of normal saline was given to the each mouse in control group according to the weight, after 2 h 0.1% CMC was given to the each mouse of control group one time by intragastric administration, then the CMC was administrated at regular time until sacrifice. All mice for other 5 groups were exposed to 100 mg/kg PQ by intragastric administration. At 2 h after exposure to PQ, 0.02 ml/10 g dexamethasone and 25, 50, 100 mg/kg PF were given to mice for dexamethasone group and for 3 PF groups by intragastric administration each day for 49 days, respectively. The lung coefficient was calculated and pathological changes of lung tissue were observed by HE staining for each mouse. The hydroxyproline (HYP) level in lung tissue was measured for each mouse. The mRNA level of and the protein level of TGF-β(1) in lung tissue for each mouse were determined, and the protein level of TGF-β(1) in the bronchus-alveolus lavage fluid (BALF) of each mouse was detected.

RESULTSThe survival rates on the 3rd day in PQ group, 3 PF groups and dexamethasone group were 53.33%, 46.67%, 73.33%, 86.67% and 80%, respectively. The survival rates on the 3rd day in dexamethasone group, 50 mg/kg and 100 mg/kg PF groups were significantly higher than those of PQ group and 25 mg/kg PF group (P < 0.05). The lung coefficients of 3 PF groups were significantly lower than that of the PQ group (P < 0.05). The lung tissue HYP levels of dexamethasone group and 3 PF groups were 50.95 ± 11.65, 44.52 ± 9.48, 43.27 ± 6.01 and 40.82 ± 5.90 mg/g respectively, which were significantly lower than that (74.27 ± 3.68) of PQ group (P < 0.01). The TGF-β(1) protein levels of BALF in dexamethasone group, 50 and 100 mg/kg PF groups were 22.03 ± 7.27, 27.75 ± 5.84 and 21.31 ± 6.82 ng/ml respectively, which were significantly lower than that (52.52 ± 15.51) ng/ml of PQ group (P < 0.01) The expression level of TGF-β(1) mRNA in 100 mg/kg PF group decreased significantly, as compared with PQ group (P < 0.01).

CONCLUSIONPF could reduce the collagen deposition and pulmonary fibrosis induced by PQ in mice lungs.

Animals ; Disease Models, Animal ; Lung ; metabolism ; pathology ; Male ; Mice ; Mice, Inbred ICR ; Paraquat ; poisoning ; Pulmonary Fibrosis ; chemically induced ; drug therapy ; pathology ; Pyridones ; therapeutic use ; Transforming Growth Factor beta ; metabolism

ONYX-015 and H101 are E1B 55-kDa protein-deficient replicating C group adenoviruses that are currently in clinical trials as antitumor agents. However, their application in cancer gene therapy is limited by the native tropism of C group adenoviruses. This is in part due to low expression of the C group adenovirus receptor (coxsackievirus-adenovirus receptor, CAR) on malignant tumors. An H101-based chimeric virus vector containing sequences encoding the Ad35 fiber domain instead of the Ad5 fiber (H101-F35) was constructed. This modification allowed infection of tumor cells through CD46, a membrane protein over-expressed on tumors. The CAR and CD46 RNA expression was evaluated by RT-PCR method. H101-F35 conferred a stronger cytocidal effect than H101 and ONYX-015 in tumor cell lines that lacked CAR expression (MDA-MB-435 and MCF-7), while the cytocidal effect of H101-35, H101 and ONYX-015 was similar in high-level CAR expressing cancer cell lines (A549, NCI-H446, Hep3B, LNCaP, ZR-75-30 and Bcap-37). In an MDA-MB-435 xenograft mouse tumor model, tumor growth in mice receiving H101-F35 was significantly inhibited compared with mice injected with H101. These results suggest that the chimeric oncolytic adenovirus H101-F35 vector might be a useful candidate for gene therapy of cancer.

OBJECTIVEThe aim of this study was to investigate whether the induction of caspase-8 by γ-interferon (IFNγ) renders neuroblastoma (NB) cells sensitive to tumor necrosis factor related apoptosis inducing ligand(TRAIL).

METHODSCaspase-8 mRNA expression was determined by RT-PCR. The effects of IFNγ, TRAIL, IFNγ +TRAIL and caspase-8 inhibitor+ TRAIL on the growth and apoptosis of NB cells were detected with the methods of reduction rate of Alamar Blue assay and flow cytometry. The relative caspase-8 activity was measured with colorimetric assay.

RESULTSCaspase-8 expression was detectable in CHP212 cells which were sensitive to TRAIL, with an increased expression after treatment with IFNγ. Caspase-8 was undetectable in SH-SY5Y(SY5Y) cells which were resistant to TRAIL, but an increased expression of caspase-8 mRNA was found after treatment with IFNγ. Moreover, TRAIL combined with IFNγ induced apoptosis in SY5Y cells. The relative caspase-8 activity of CHP212 cells increased with the prolonged TRAIL action time. The relative caspase-8 activity of SY5Y cells in the IFNγ+TRAIL group was significantly higher than those of the control, IFNγ, TRAIL and inhibitor groups.

CONCLUSIONSNB cells expressing caspase-8 are sensitive to TRAIL. TRAIL induces apoptosis in NB cells with an increase of relative caspase-8 activity.

Apoptosis ; drug effects ; Caspase 8 ; physiology ; Cell Line, Tumor ; Flow Cytometry ; Humans ; Interferon-gamma ; pharmacology ; Neuroblastoma ; drug therapy ; pathology ; Reverse Transcriptase Polymerase Chain Reaction ; TNF-Related Apoptosis-Inducing Ligand ; pharmacology

OBJECTIVETo explore the clinical efficacy of the percutaneous kyphoplasty for the treatment of osteoporotic Kummell's disease.

METHODSFrom May 2010 to February 2012, 8 patients with osteoporotic Kummell's disease were treated with percutaneous balloon kyphoplasty. There were 2 males and 6 females, with a mean age of 73.4 years. All the patients suffered from lower back pain for 4.7 months, which affected seriously the patient's quality of life. The anterior vertebral height and Cobb angel was measured on standing lateral radiograph at pre- and post-operatively (2 days after operation) and during the final follow-up. Visual analog scale (VAS), Japanese Orthopedic Association (JOA) and Oswestry disability index (ODI) were used to evaluate pain and function.

RESULTSIncision of all patients healed normally without infection. The level of back pain decreased remarkably after surgery. The mean time of ambulation was 4.3 days (ranged, 1 to 10 days). Cement leakage occurred in 1 case with no symptom. The anterior vertebral height and Cobb angel of the fractured vertebra recovered respectively from preoperative (30.4 +/- 7.4)% and (31.3 +/- 9.9) degree to (70.3 +/- 3.3)% and (9.1 +/- 3.0) degree at the 2nd day after operation. VAS and JOA scores, ODI improved from preoperative 8.7 +/- 1.2, 12.3 +/- 1.7 and (93.3 +/- 4.6)% to 3.1 +/- 1.1, 24.9 +/- 1.6 and (32.2 +/- 5.4)% respectively at the 2nd day after operation. All the patients were followed up, and the duration ranged from 3 to 24 months, with a mean of 4.7 months. At the latest follow-up, the anterior vertebral height and Cobb angel of the fractured vertebra were (69.9 +/- 3.2)% and (10.9 +/- 2.4) degree; the VAS and JOA scores and ODI were 2.2 +/- 1.0, 26.4 +/- 1.4 and (29.2 +/- 4.5)% respectively, which had no obvious difference compared to those results at the 2nd day after operation.

CONCLUSIONBalloon kyphoplasty is safe and effective treatment for osteoporotic Kummell's disease.

Aged ; Aged, 80 and over ; Female ; Humans ; Kyphoplasty ; methods ; Male ; Osteoporosis ; surgery ; Treatment Outcome

BACKGROUND:Schwann cells are important celllines in the process of repairing peripheral nerve injury, and human amniotic homogenate supernatant is shown to secrete a variety of cytokines, which could promote the proliferation of Schwann cells.
OBJECTIVE:To investigate the effect of different concentrations of human amniotic homogenate supernatant on the proliferation of rat Schwann cell96.
METHODS:Schwann cell96 was cultured with high-glucose DMEM containing 20%fetal bovine serum, and the second generation of Schwann cell96 was applied for experiments. The cultured cells were divided into five groups according to different volume fractions of human amniotic homogenate supernatant (0%, 10%, 15%, 20%, 25%) in the medium.
RESULTS AND CONCLUSION:The total protein concentration of human amniotic homogenate supernatant was 675μg/mL, in which the concentration of epidermal growth factor, basic fibroblast growth factor and vascular endothelial growth factor were respectively (470.625±2.546), (4.121±0.026) and (0.172±0.002) ng/L. At 1-7 days, the cellproliferation rate of the 10%and 15%concentration groups was greater than that in 20%and 25%concentration groups (P<0.05);10%and 15%concentrations promoted cellproliferation, while 20%and 25%concentrations inhibited cellproliferation. There were no significant difference in the viability of Schwann cell96 between the control group and the experimental group (P>0.05). Low concentrations (10%, 15%) of human amniotic homogenate supernatant promote the proliferation of Schwann cell96, while high concentrations (20%, 25%) of human amniotic homogenate supernatant inhibit cellproliferation.