Child ; Clinical Trials as Topic ; ethics ; Drugs, Investigational ; Humans

Aged ; Antineoplastic Agents ; therapeutic use ; Benzamides ; therapeutic use ; Drug Resistance, Neoplasm ; Exons ; Gastrectomy ; methods ; Gastrointestinal Neoplasms ; drug therapy ; metabolism ; pathology ; surgery ; Gastrointestinal Stromal Tumors ; drug therapy ; metabolism ; pathology ; surgery ; Humans ; Imatinib Mesylate ; Liver Neoplasms ; drug therapy ; secondary ; Male ; Piperazines ; therapeutic use ; Point Mutation ; Proto-Oncogene Proteins c-kit ; genetics ; metabolism ; Pyrimidines ; therapeutic use

Objective To discuss the therapeutic effect of transcatheter arterial embolization using hardening agent combined with oral propranolol in treating giant hemangioma at maxillofacial region in infants. Methods During the period from October 2013 to December 2014 at Imaging Center of Anhui Provincial Children's Hospital, transcatheter arterial embolization using hardening agent combined with oral propranolol was employed in a total of 27 infants with giant hemangioma at maxillofacial region. The age of the infants ranged from 2 months to 22 months (mean 5.9 months) and the body weight was 4.5-10 kg with a mean of 6.32 kg. Angiography via femoral artery was performed, which was followed by super-selective catheterization of hemangioma-feeding artery, and then pingyangmycin lipiodol emulsion was injected into the hemangiomas with subsequent injection of PVA particles to obstruct the hemangioma-feeding artery. After the embolization treatment, the patient received oral propranolol for 3-6 months. Results All the infant patients were followed up for 3-6 months. Clinical examination and ultrasonography indicated that the hemangioma was cured in 20 infants (75%) and the therapeutic result was effective in 7 infants (25%). Skin necrosis at hemangiomas site was observed in 2 infants (7.5%), which was cured after symptomatic treatment. No serious complications such as pulmonary embolism, cerebral embolism occurred, and no recurrence was observed. Conclusion For the treatment of giant hemangioma at maxillofacial region in infants, transcatheter arterial embolization using hardening agent combined with oral propranolol is minimally invasive, quickly effective and highly safe;and this treatment leaves no scar formation in most cases. Therefore, this technique is worthy of clinical application.

Objective To investigate the percentages of Th17 and CD4+CD25+FoxP3+ regulatory T(Tr) cells and the levels of related cytokines IL-6,IL-23,IL-17 and TGF-β in serum of patients with anlylosing spondylitis(AS).Methods Forty patients with AS and 37 age-matched healthy donors were studied.Flow cytometry Was used to analyze the percentages of blood Th17 and CD4+CD25+FoxP3+Tr cells.The levels of serum IL-6,IL-23,IL-17 and TGF-β were assayed by enzyme-linked immunosorbent assay ( ELISA).Results The proportion of Th17 cells in AS group was significantly higher than those in normal group [ (1.02±0.34)％ vs (0.68±0.29)％,P＜0.05) ],and the proportion of CD4+CD25+FoxP3+ cells was lower in AS group comparing with normal group [(3.77±0.81)％ vs (4.69±1.23)％,P＜0.05)].Meanwhile,serum levels of IL-6,IL-23 and IL-17 were significantly higher in AS group than those in normal group [ (6,15±2.71) ng/L vs (3.31±1.65) ng/L; (9.44±3.12) ng/ml vs (5.82±2.61) ng/ml;(10.53±4.97) ng/L vs (6.78±3.26) ng/L,all P＜0.01 ].In contrast,TGF-β level was decreased in AS group compares with the normal group [ ( 4.76±2.15) ng/ml vs (5.16±2.02) ng/ml,P＞0.05 ],but the difference was not significant.No associations of serum eytokine levels with clinical and laboratory parameters were found in AS.Conclusion The abnormality Th17 cells and Tr cells and their related cytokines IL-6,IL-23,IL-17 and TGF-β changes in patients with AS,which may be involved in immunological pathogenesis of AS.

Objective To prepare a novel extravascular human epithelial growth factor receptor 2 (HER2)-targeted polylactic-co-glycolic acid (PLGA)-COOH ultrasound contrast agent with liquid perfluorocarbons(PFH-PLGA-tra),and to observe it's general properties and it's effects on ultrasound imaging in vitro.Methods Polymeric nanocapsules of liquid perfluorocarbons were prepared by the single emulsion technique and conjugated with trastuzumab monoclonal antibody by EDC/NHS.The general characteristics were observed.The conjugation was demonstrated by immunofluorescence and the targeting performance of the agent was checked in human MCF-7 cells line in vitro.The encapsulation of liquid fluorocarbons was detected by heating in vitro.The effects on ultrasound imaging were observed in vitro.Results The mean diameter of agents was (261 ± 28)nm.The targeted nanocapsules were positive in immunofluorescence.In the targeted study,it was shown that a number of targeted nanocapsules conjugated with MCF-7 cells in vitro.Droplet-to-bubble transition experiment in vitro showed that there were no nano/microbubbles formed by heating in control groups at 80℃,while there were a lot of nano/microbubbles appeared in nanocapsules formulations at 80 ℃.The agents presented a good ultrasound imaging in vitro.Conclusions The HER2-targeted polymeric nanocapsules of liquid perfluorocarbons are successfully prepared,which may become a novel extravascular targeted ultrasound contrast agents.

objective To observe the distribution of vitamin D receptor(VDR)gene polymorphisms in children of Han nationality and investigate the relationship between VDR gene polymorphisms and the susceptibility to children's dental fluorosis of Han nationality.Methods From October of 2008 to March of 2009,a case-control study was conducted among children between 8 and 12 years old with(n=101)and without(n=102)dental fluorosis using Dean method in Guandian countyside of Fengtai county in Anhui province.DNA was extracted from blood samples ofthese children.The Apa I,Bsm I,Fok I and raq I polymorphisms in the VDR gene were genotyped using polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP).The distribution of the genotypes in patients and the control group were analyzed. Results Different genotypes of the VDR gene existed in children of Han nationality with the highest distribution frequency of Aa, bb, Ff, TT, which respectively was 51.7% ( 105/203 ), 89.7% (182/203), 52.7% (107/203), 93.1% (189/203), followed by genotype distribution frequency of aa, Bb, FF, Tt, being 39.9% (81/203),7.9% (16/203),31.5% (64/203) ,6.9% (14/203), respectively. AA,BB, ff, tt distribution frequency was the lowest as follows, 8.4% ( 17/203 ), 2.4% (5/203), 15.8% (32/203),0 (0/203). The frequency distribution of VDR Apa I genotype was AA 7.9% (8/101), Aa 55.4% (56/101), aa 36.7%(37/101) in children with fluorosis, and AA 8.8% (9/102), Aa 48.0% (49/102), aa 43.3% (44/102) in children without fluorosis, respectively. There were no significant differences in the two groups(χ2= 1.13, P > 0.05).The frequency distribution of VDR Bsm I genotype was BB 3.0%(3/101), Bb 5.9%(6/101 ), bb 91.1% (92/101) in children with fluorosis, and BB 2.0% (2/102), Bb 9.8% (10/102), bb 88.2% (90/102) in children without fluorosis, respectively. There were no significant differences in the two groups(χ2 = 0.55, P > 0.05). The frequency distribution of VDR Fok I genotype was FF 28.7%(29/101), Ff 56.4% (57/101), ff 14.9%(15/101) in children with fluorosis, and FF 34.3% (35/102), Ff 49.0% (50/102), ff 16.7% (17/102) in children without fluorosis,respectively. There were no significant differences in the two groups(χ2 = 1.14, P > 0.05). The frequency distribution of VDR Taq I genotype was TT 93.1%(94/101), Tt 6.9%(7/101) in children with fluorosis, and TT 93.1% (95/102), Tt 6.9%(7/102) in children without fluorosis, respectively. The tt genotype was not found. There were no significant differences in the two groups (χ2 = 0.00, P > 0.05 ). Conclusions Different genotypes of the VDR gene existed in children of Han nationality. There were no correlation between VDR Apa I , Bsm I , Fok I , Taq I gene polymorphisms and children's dental fluorosis of Han nationality in this area.

Objective To examine the effects and mechanisms of siRNA targeting aquaporin 4 (AQP 4) in combination with hyperbaric oxygen therapy(HBO) on cerebral edema and apoptosis in the brain tissue of rats after hemorrhage.Methods Rats were randomly divided into four groups,the control group,the hyperbaric oxygen group,the AQP-4 siRNA group and the combination therapy group (24 rats).Thrombin Ⅶ was injected into the caudate nucleus to establish the hemorrhage model.Construction of siRNA targeting aquaporin 4 was conducted.The mRNA expression of AQP-4 was detected by RT-PCR at day 3.Changes in brain moisture and blood-brain barrier perme ability were measured by a wet/dry weight method and Evans blue fluorometry.The nerve cell apoptosis rate was analyzed by Annexin V andTdT-mediated dUTP-biotin nick end labeling (TUNEL).The expression of proteins including AQP-4,MMP-2,MMP-9,Bcl-2 and caspase-3 was detected by Western Blotting.All the animals were given a score for their nerve function at day 3.Results AQP-4 siRNA treatment obtained better effects than HBO in decreasing the brain edema leveland silencing AQP-4 mRNA(P＜0.05)while,the combination therapy group achieved the best results(P＜ 0.05).Compared with the control group,the percentage of apoptotic cells decreased in all the three treatment groups,with the most marked decrease observed in the combination treatment group(4.24± 0.04)％(F=13.76,P=0.001).The expression of AQP-4,MMP-2,MMP-9 and caspase-3 was lower (P＜0.05) and the expression of Bcl-2 was higher(P＜0.01)in the combination treatment group than in the other three groups.Compared with the control group,all the other three groups received better scores on nerve function defect evaluation at day 3 after hemorrhage(P＜0.05),with the combination treatment group again achieving the most favorable score (4.7 ± 1.1) (F=7.21,P =0.013).Conclusions Targeted siRNA interference combined with hyperbaric oxygen can effectively reduce cerebral edema after cerebral hemorrhage,inhibit neuronal apoptosis and promote neuron function recovery.The underlying mechanisms may be related to down-regulation of AQP-4,MMP 2,MMP-9 and caspase-3 expression and up-regulation of Bcl-2 expression.

OBJECTIVETo investigate the anti-metastatic effect of vascular endothelial growth factor receptor 2 extracellular domain gene-modified dendritic cell (DC-sVEGFR-2) vaccination.

METHODSDendritic cells (DC) were electroporated with pcDNA3. 1/sVEGFR-2 plasmid DNA. Expression of sVEGFR-2 was determined by ELISA. For immunization, C57BL/6 mice were intravenously injected three times with 1 x 10(5) cells per mouse of DC, pcDNA3. 1-transfected DC (DC-vector) , DC-sVEGFR-2, or 100 microl of PBS at 7-day intervals. At 10 days after the last immunization, the immunized mice were subjected to assessment of cytotoxic T lymphocyte ( CTL) response to VEGFR-2, alginate bead analysis of tumor cell-induced angiogenesis, and observation of the anti-metastatic effect in B16 melanoma metastasis model. CTL activity was determined by a standard 4-h 51Cr release assay against VEGFR-2 + vascular endothelial cell line H5V, 3LL cells stably transfected with pcDNA3. 1/sVEGFR-2 (3LL,-sVEGFR-2), and VEGFR-2- cell lines EL-4 and 3LL. Monoclonal antibodies GK1.5 anti-CD4 and 2.43 anti-CD8 were used to deplete in vivo CD4 + T cells and CD8' T cells, respectively.

RESULTSDC-sVEGFR-2 could effectively express sVEGFR-2, whereas DC-vector and DC could not. Immunization of mice with DC-sVEGFR-2 significantly induce CTL activity against VEGFR-2 + cell lines H5V and 3LL-sVEGFR-2, however, no significant CTL activity was observed when VEGFR-2- syngeneic cell lines EL-4 and 3LL. were used as target cells, implying this CTL activity was VEGFR-2 specific. Alginate bead analysis of in vivo neoangiogenesis showed that the inhibition reached 50% in mice vaccinated with DC-sVEGFR-2 compared with mice vaccinated with DC, DC-vector or PBS. Anti-metastatic experiment showed that profound reduction in pulmonary metastases was found in mice immunized with DC-sVEGFR-2, while mice immunized with PBS, DC, DC-vector developed extensive pulmonary metastases. The number of tumor nodules on lung surface decreased by 81.9% in mice immunized with DC-sVEGFR-2 when compared with mice immunized with DC-vector (49.7+/-12.7 vs. 9.0+/-3.2). In vivo T cell subset depletion experiments showed that the anti-metastatic effect of DC-sVEGFR-2 vaccination was abrogated in CD8 + T cell-depleted but not in CD4+ T cell-depleted mice.

CONCLUSIONImmunization of mice with DC-sVEGFR-2 could break self-tolerance and induce a significant CTL response to VEGFR-2, leading to profound inhibition of tumor-cell induced angiogenesis and metastasis. This anti-metastatic effect is mainly mediated by CD8+ T cells.

Animals ; CD8-Positive T-Lymphocytes ; immunology ; Cancer Vaccines ; immunology ; Carcinoma, Lewis Lung ; blood supply ; immunology ; pathology ; Cell Line, Tumor ; Dendritic Cells ; immunology ; metabolism ; Electroporation ; Female ; Immunotherapy, Adoptive ; methods ; Lung Neoplasms ; secondary ; therapy ; Mice ; Mice, Inbred C57BL ; Neovascularization, Pathologic ; immunology ; therapy ; T-Lymphocytes, Cytotoxic ; immunology ; Vascular Endothelial Growth Factor Receptor-2 ; biosynthesis ; genetics

Objective To investigate the brain mechanisms of aging of the visual attention. Methods Through the precue-target visual search paradigm using the event-related potentials technique,16 young and 16 elderly subjects participated the electrophysiological experiment.The background was comprised of three homocentric black circles and eight English capital letters consisted of each circle.The letter “T” was designed as the target stimulus.T was a target only when it located the circle clued to the same size of the precue.For example,when the cue was the “large”,“T” may appear within 3 circles.When the cue was the “median”,“T” may appear within either the median or small circles.When the cue was small,the target “T” may appear only within the small circle. Results The reaction time of the two groups of subjects became quick with the reduction of the cue scale,while the amplitudes of P1 and N1 components of event-related potentials increased with the decrease of the cue scale.Old subjects showed longer response time than did young subjects,and the posterior P1 component was enhanced significantly and N1 component was inhibited obviously.The P2 component was manifested as significantly inhibitory effect not only in the amplitude but also in the abnormal and unstable waveform.Conclusions The cognitive function of elderly subjects declines in the research of target stimuli,which suggests that the age-related changes could lead to deficit in the posterior area of the brain to visual spatial attention (involuntary attention).

Recent years have seen an increasing incidence of prostate cancer (PCa) and a more frequent occurrence of the disease in younger men. Damage to cavernous nerves caused by radical prostatectomy is the main reason for post-operative erectile dysfunction. So reconstruction of cavernous nerves at the time of radical prostatectomy may restore the patient's erectile function. At present, clinical studies of using autologous sural nerve grafts to bridge transected cavernous nerves have achieved modest success, and laparoscopic sural nerve grafting during radical prostatectomy has also been proved safe and feasible. Besides, various grafts have been used to reconstruct cavernous nerves in animal models, among which biodegradable conduits containing growth-promoting factors or cells are a promising option for the repair of damaged cavernous nerves.
Animals ; Erectile Dysfunction ; etiology ; surgery ; Humans ; Male ; Nerve Regeneration ; Neurosurgical Procedures ; methods ; Penis ; innervation ; Prostatectomy ; adverse effects ; Prostatic Neoplasms ; surgery ; Rats ; Sural Nerve ; transplantation