Background Radiation-induced optic neuropathy (RION) is a severe complication after radiotherapy for head and neck cancer,which threatens the visual acuity and quality of life of patients.Till now,there is no recognized treatment for RION.It is of great significance to study the natural progression of the RION,and to prevent and treat RION.Objective This study was to establish an ideal radioactive optic nerve injury animal model.Methods Healthy 8-week SD rats with hygiene grade were randomly divided into normal control group and model group,with 6 rats in each group.The total 30 Gy dose of radiation with 3 portions was used to irradiate the head model group rats;ELISA was performed to analysis the changes of endothelin-1 (ET-1) and Von Willebrand factor (vWF) concentrations in blood 2,4 and 8 weeks after irradiation.Hematoxylin-eosin staining and transmission electron microscope were performed to observe the changes of optic structure.The use and care of the experimental animals complied with the ARVO statement.Results The concentrations of ET-1 in the model group were (23.18± 0.11),(27.98 ±0.22),(33.90 ±0.1 1),(65.25 ±0.38) and (43.82 ± 0.09) pg/ml before irradiation,1 day,2,4,6 weeks after irradiation,those in the normal control group were (22.65 ± 0.14),(23.18 ± 0.19),(23.68 ± 0.15),(24.23±0.12) and (23.58±0.16)pg/ml.The concentrations of vWF in the model group were (63.16±2.21),(88.32± 2.06),(123.38 ± 1.36),(191.40 ± 0.61) and (141.69 ± 0.82) pg/ml before irradiation,1 day,2,4,6 weeks after irradiation,those in the normal control group were (62.82 ± 1.56),(63.35 ±2.06),(64.12 ± 1.76),(63.52±2.02) and (63.48 ± 1.55)pg/ml.There were significant differences of ET-1 and vWF concentrations among different groups and time points (ET-1:Fgroup =32.160,P =0.012;Ftime =21.180,P =0.023.vWF:Fgroup =73.110,P=0.001;Ftime =46.180,P =0.002).The nerve fiber bundles was swelled with disordered arrangement and vacuolization 8 weeks after irradiation.Axon swell and atrophy,axons with myelin sheath layer plate separation were obtained.The rates of axon demyelination in the normal control group and model group were (1.35 ±0.79) ％ and (14.44±2.32)％,respectively.There was a statistically significant difference between the two groups (t =14.07,P＜0.01).Conclusions The total 30 Gy dose of radiation on the head of rats can make stable radioactive optic nerve injury model.This model making method is simple,cheap and practical,which is worth further study.

AIM: To investigate the behaviour of 3T3 fibroblast and macrophage co-culture on blood fibrin clot or adipose tissue with recombinant basic fibroblast growth factor (rhbFGF). METHODS: MTT method, inverted contrast microscopy, Giemsa staining as well as scanning electron microscope were used in the present study. RESULTS: The effect of rhbFGF on co-culture of 3T3 fibroblast and mouse macrophage on blood fibrin clot in low-serum DMEM with rhbFGF were monitored, and 3T3 fibroblast and macrophage growed well on the blood fibrin blot in low-serum DMEM with rhbFGF. CONCLUSION: The blood fibrin clot, with its low immunogenicity, could be used as a bionic support for three-dimensional tissue culture, and also a physiological carrier to distribute the growth factor rhbFGF for the cells.

Objective:To describe the clinical characteristics , overall survival as well as to evaluate the prognostic factors in Chinese diffuse large B cell lymphoma ( DLBCL) patients.Methods: DLBCL pa-tients who were initially diagnosed and treated in Peking University Cancer Hospital from January 1995 to December 2008 were identified and analyzed ,retrospectively .The 5-year OS rates were estimated with Ka-plan-Meier.Log-rank test was used to compare the survival curves of the different groups .The multivari-ate analysis of prognostic factors was conducted with Cox regression model , which included all statistically significant prognostic factors in the univariate analyses .Results:A total of 525 DLBCL patients were in-cluded in this retrospective analysis , of whom , 294 were male and 231 female ( male∶female=1 .27∶1 ) . The median age at the initial diagnosis was 55 (range 16-90) years, and 37.0% (n=194) were 60 years and above .Regarding the clinical staging at the initial diagnosis , 54 patients (10.3%) were diag-nosed as Stage Ⅰ of the disease, 152 (28.9%) as Stage Ⅱ, 117 (22.3%) as Stage Ⅲ and 202 (38.5%) as Stage Ⅳ.The ‘B symptoms’ and increased serum LDH were presented in 206 (39.2%) and 192 (36.6%) patients, respectively.A total of 197 (37.5%) patients were treated with rituximab (R).The survival follow-up continued till 31 January 2014 with a median follow-up time of 77.5 ( range:0-205) months.A total of 267 patients (50.9%) died during the follow-up period.The medi-al overall survival ( OS) time was 84 months, and 5-year OS rate was 52.3%.There were six statistically significant prognostic factors that were identified in both univariate and multivariate analyses : gender, Ann Arbor stage, B symptom, serum LDH, age at initial diagnosis and rituximab treatment .The relative risk ( RR) of these prognostic factors in the multivariate analyses were: age >60 years /≤60 years=1.380 (95%CI 1.078 -1.765), male /female =1.315 (95%CI 1.025 -1.687), stage Ⅲ/stageⅠ=3.034(95%CI 1.667-5.522), stage Ⅳ/Ⅰ=3.748(95%CI 2.102 -6.681), with B symp-toms/without B symptoms=1.278(95%CI 0.999-1.636),serum LDH increased/LDH not increased=1.351(95%CI 1.057 -1.726), without R treatment /with R treatment =1.543(95%CI 1.182 -2 .015 ) .Compared with the IPI , age >50 years/≤50 years was a statistically significant factor in both univariate and multivariate analyses RR =1.478 (95%CI 1.148-1.902), P=0.002.Conclusion:Six factors were related to DLBCL survival:gender, Ann Arbor stage, B symptom, serum LDH, age at initial diagnosis and rituximab treatment .Compared with the IPI , several specific factors may predict a poor prognosis in Chinese DLBCL patients:male , age>50 years and the presence of ‘B symptoms ’ .But this result is not conclusive until these factors are further tested .

Objective To investigate the phenotypes and the HIV-1-specific T cell responses of KIR3DL1 positive CD8 cells in patients with early HIV-1 infection. Methods Fifty-six HIV-1 antibody negative individuals and thirty-two patients with early HIV-1 infection were enrolled in the study. Fluores-cence-activated cell sorting (FACS) was performed to detect the phenotypes of KIR3DL1 receptor expressed on the surface of CD8 cells. The levels of IFN-γwere measured by intracellular cytokine staining assay after the PBMCs were stimulated with an HIV-1 Gag peptide pool. Results The percentages of KIR3DL1+CD8 T cells in HIV-1 negative individuals and patients with early HIV-1 infection were 1. 45% (0. 12%-8. 4%) and 0. 82% (0. 14%-6. 14%), respectively, and there was no significant difference between them. The percentages of KIR3DL1+CD8 Temra cells in HIV-1 negative individuals and patients with early HIV-1 infec-tion were (4. 55±3. 84)% and (6. 71±8. 50)%, respectively, which were significantly higher than the per-centages of KIR3DL1+CD8 Tem cells, which were (0. 50±0. 59)% and (1. 18±1. 39)%, respectively (all P<0. 01). Moreover, the percentages of KIR3DL1+CD8 Tem cells in patients with early HIV-1 infection were higher than those in HIV-1 negative individuals (P=0. 001 2). The percentage of KIR3DL1+CD8 Temra cells was positively correlated with the HIV-1 viral load in patients with early HIV-1 infection ( rs=0. 576,P=0. 000 9). The percentages of KIR3DL1+CD8 Temra cells in HIV-1 patients, whose viral loads were larger than 4. 0log, were much higher than those in HIV-1 patients with viral loads less than 4. 0 log (P=0. 002). Additionally, the levels of IFN-γsecreted by KIR3DL1 positive CD8 cells were much lesser than those secreted by KIR3DL1 negative CD8 cells (P<0. 000 1). Conclusion The receptor of KIR3DL1 was mainly expressed on CD8 Temra cells in both HIV-1 negative subjects and patients with early HIV-1 infec-tion. High HIV-1 viremia was associated with the high percentage of KIR3DL1+CD8 Temra cells. The KIR3DL1 positive CD8 cells induced lower HIV-1-specific T cell responses.

Objective To evaluate the preventive effect of orifices-dredging and stasis-removing therapy on retinal vascular endothelium and optic nerve damage induced by radiation in rats. Methods Thirty-six SD rats were randomly divided into 3 groups, namely blank control group, model group and therapy group. Rats in the model group and therapy group were exposed to X-ray radiation once a week for three weeks. Two weeks before the radiation, therapy group was pretreated with intraperitoneal injection of Astragalus injection ( 4.0 g/kg) , Ligustrazine Hydrochloride injection ( 15 mg/kg) and Xingnaojing injection ( 2.5 mL/kg) once a day, blank control group and model group were given intraperitoneal injection of same volume of saline once a day. Before radiation, one day, and 2, 4 and 6 weeks after radiation, we detected the blood concentrations of endothelin-1 ( ET-1) and Von willebrand factor (vWF) in all of the rats by enzyme-linked immunosorbent assay (ELISA) , and analyzed the dynamic changes and intergroup difference. Demyelination of optic nerve was observed under transmission electron microscope, and demyelination percentage was counted 2, 4, and 6 weeks after irradiation. Results Compared with the blank control group, the blood concentrations of ET-1 and vWF in model group were increased after irradiation (P<0.05) , and the peak value appeared on the fourth week after irradiation. Compared with the model group, the blood concentrations of ET-1 and vWF in the therapy group were decreased weeks 2 after irradiation ( P<0.05) . The demyelination percentage of optic nerve was significantly higher in the model group than that in the blank control group (P<0.05) 2, 4, and 6 weeks after irradiation. Compared with the model group, the demyelination percentage of optic nerve in therapy group showed insignificant changes 2 and 4 weeks after irradiation (P>0.05) , but was decreased obviously 6 weeks after irradiation (P<0.05) . Conclusion Pretreatment with orifices-dredging and stasis-removing therapy can decrease the blood concentrations of ET-1 and vWF in the radiation-induced retinal damage rats, and can reduce the demyelination of optic nerve in irradiated rats.

ObjectivesTo identify the related abnormalities of gray matter in pediatric patients with Tourette syndrome (TS) by using the optimized voxel-based morphometry (VBM).Methods Three dimensional T1WI was acquired in 31 TS children (28 boys,3 girts,mean age 8 years,range 4-15 years) and 50 age- and sex-matched controls on a 1.5 Tesla Philips scanner. Images were pre-processed and analyzed using a version of VBM 2 in SPM 2.The whole brain gray matter volume was compared between the study and control group by using t-test.Multivariate linear regression analysis was used for analyzing the correlation between the change of grey matter volume within each brain region (mm3 ) and YGTSS score and course of disease of TS patients.Statistical analyses were performed by using SPSS 13.0.ResultsUsing VBM,significant increases in gray matter volumes in left superior parietal lobule, right cerebellar hemisphere and left parahippocampal gyrus were detected in TS patients,and the volume changes were 4059,2126 and 84 mm3 ( t =3.93,3.71,3.58,P ＜ 0.05 ) respectively.Compared to the control group,decreased grey matter volumes were found in medulla and left pons,and the volume changes were 213 and 117 mm3( t =3.53,3.48,P ＜ 0.05 )respectively.Tic severity was not correlated with any volume changes of gray matter in brain (P ＞ 0.05,a small volume correction,KE ≥ 10 voxel).Tic course was negatively correlated with the gray matter volume of left parahippocampal gyrus ( Beta =- 0.391,P =0.039 ).ConclusionsUsing VBM technique,the gray matter abnormalities can be revealed in TS patients without obvious lesions on conventional MR imaging.The increasing volume of temporal and parietal lobes and cerebellar may be an adaptive anatomical change in response to experiential demand. The gray matter volume of the parahippocampal gyrus may be used as one potential objective index for evaluating the prognosis of TS.

OBJECTIVETo investigate the effects of pyrethroids on the concentrations of thyroid hormone in rat brain.

METHODPermethrin (PM) and deltamethrin (DM) were administered to the rats with daily doses of 100, 200 and 400 mg.kg-1.d-1 and 6.25, 12.5 and 25 mg.kg-1.d-1, respectivelly for 15 days. Serum and brain tissue determinations of thyroxin (T4) and triiodothyronine (T3) were performed by radioimmunoassay (RIA).

RESULTSPM induced a dose dependent decrease in the serum levels of T4, T3, fT4 and fT3 and an increase in the serum TSH levels, whereas DM was only able to induce a dose dependent decrease in the serum levels of T4. PM treatment reduced both the levels of T4 and T3 in homogenates of the cerebral cortex and hippocampus respectively, whereas the highest dose of DM decreased only the cerebral cortex levels of T4. The effects of subchronic treatment with PM and DM on the concentrations of T3 were further investigated in the subcellular fractions, namely nuclei, mitochondria, myelin and synaptosomes of the cerebral cortex and hippocampus. PM treatment induced a decrease in the nuclear and synaptosomal concentrations of T3 of either the cerebral cortex or hippocampus, whereas DM reduced the levels of T3 especially in the mitochondria of the cortex and hippocampus.

CONCLUSIONSTreatment with pyrethroids subchronically to the rats would affect the serum and brain tissue levels of T4 and T3. These results indicate that the pyrethroids-induced neurotoxicity may involve at least in part an impairment of the physiological action of T3 at its subcellular targets.

Animals ; Brain Chemistry ; drug effects ; Cell Nucleus ; chemistry ; drug effects ; Dose-Response Relationship, Drug ; Insecticides ; toxicity ; Nitriles ; toxicity ; Permethrin ; toxicity ; Pyrethrins ; toxicity ; Radioimmunoassay ; Rats ; Synaptosomes ; chemistry ; drug effects ; Thyroid Hormones ; analysis ; blood

Attention deficit hyperactivity disorder (ADHD) is a common neurodevelopmental disorder among children and adolescents, and it is commonly accompanied with other developmental and psychological disorders.The prevalence of obesity in children continues to rise, and it is also a major social public concern that threatens human health.As a somatic comorbidity with ADHD, obesity is characterized by a high incidence.In this paper, the focus would be placed on the underlying mechanisms of ADHD accompanied with obesity from the aspects of genetics, perinatal period, environmental and neurobiological factors, which could provide a theoretical basis and intervention strategies for the early identification, rational treatment and long-term comprehensive management, as well as prevention and treatment effects of ADHD and its comorbidities.

Objective:To investigate whether rumination and family functioning can predict the level of depression after 1 year of follow-up in patients with first-episode depression, and whether family functioning plays a mediating role between rumination and depression level.Methods:Sixty-five patients with first-episode depression who met the enrollment requirements were included, and all subjects were assessed the 17-item Hamilton depression scale(HAMD-17), rumination response scale(RRS) and family assessment device(FAD). All subjects were followed up for 1 year, and the predictive effects of rumination and family functioning at baseline on the level of depression after 1 year of follow-up were investigated by hierarchical linear regression analysis and mediation analysis.Results:At the baseline stage, rumination, role, affective involvement (AI) and general functioning (GF) were significantly positively associated with depression level after 1 year of follow-up in patients with first-episode depression ( r=0.49, P<0.01; r=0.30, P=0.02; r=0.43, P<0.01; r=0.50, P<0.01; respectively). Rumination, AI and GF at the baseline stage predicted depression level after 1 year of follow-up ( β=0.315, t=2.954, P=0.005; β=0.261, t=2.550, P=0.013; β=0.323, t=2.952, P=0.005). Mediation analysis showed that AI and GF partially mediated the relationship between rumination at baseline and depression level at 1 year follow-up (point estimate value for AI=0.040, 95% CI=0.012-0.090); point estimate value for GF=0.066, 95% CI=0.017-0.143). Conclusions:Rumination and family functioning at baseline in first-episode depressed patients can predict the depression level at 1 year follow-up.Family functioning partly mediates the relationship between the baseline rumination and the depression level at 1 year follow-up.

Objective:To predict and evaluate the antibacterial efficacy of linezolid, teicoplanin and daptomycin against Staphylococci bloodstream infections with Monte Carlo simulation, and to optimize the clinical administration program. Methods:A total of 1 847 Staphylococci strains isolated from blood samples between January 2018 to December 2019 were collected with the help of the Blood Bacterial Resistant Investigation Collaborative System (BRICS). Minimum inhibitory concentrations (MIC) of linezolid and daptomycin were detected by broth dilution method, while MIC of teicoplanin were detected by agar dilution method. The dosage regimens of linezolid were 800 mg once daily, 500 mg once every 12 hours, 600 mg once every 12 hours and 600 mg once every eight hours. The dosage regimens of teicoplanin were 400 mg once every 12 hours, 600 mg once every 12 hours, 800 mg once every 12 hours, and 1 000 mg once every 12 hours. The dosage regimens of daptomycin were 4 mg·kg -1·d -1, 6 mg·kg -1·d -1, 8 mg·kg -1·d -1, 10 mg·kg -1·d -1and 12 mg·kg -1·d -1. The probability of target attainment (PTA) and cumulative fraction of response (CFR) of three different dosage regimens were calculated by Monte Carlo simulation. A dosage regimen with CFR≥90.0% was a reasonable choice for empirical antimicrobial therapy. Results:PTA of linezolid against Staphylococci when MIC≤0.500 mg/L at four dosage regimens (800 mg once daily, 500 mg once every 12 hours, 600 mg once every 12 hours and 600 mg once every eight hours) were all over 90.0%. When MIC was 1.000 mg/L, the PTA of linezolid against Staphylococci under the dosages of 500 mg once every 12 hours, 600 mg once every 12 hours and 600 mg once every eight hours were 92.2%, 96.6% and 97.6%, respectively. The CFR of the four dosage regimens of linezolid were 73.9%, 83.7%, 90.8% and 95.3%, respectively. When MIC≤1.000 mg/L, PTA of teicoplanin against Staphylococci were all 100.0% at four dosage regimens (400 mg once every 12 hours, 600 mg once every 12 hours, 800 mg once every 12 hours and 1 000 mg once every 12 hours). When MIC was 2.000 mg/L, the PTA of teicoplanin (800 mg once every 12 hours and 1 000 mg once every 12 hours) against Staphylococci were both 100.0%. The CFR of the four dosage regimens of teicoplanin were 90.8%, 92.8%, 93.5% and 94.6%, respectively. When MIC≤0.500 mg/L, PTA of daptomycin against Staphylococci under the five dosages of 4 mg·kg -1·d -1, 6 mg·kg -1·d -1, 8 mg·kg -1·d -1, 10 mg·kg -1·d -1 and 12 mg·kg -1·d -1 were all over 90.0%. When MIC was 1.000 mg/L, the PTA of daptomycin against Staphylococci under the three dosages of 8 mg·kg -1·d -1, 10 mg·kg -1·d -1 and 12 mg·kg -1·d -1were 96.9%, 100.0% and 100.0%, respectively. The CFR of the five dosage regimens of daptomycin against Staphylococci were 97.4%, 99.2%, 99.9%, 100.0% and 100.0%, respectively. Conclusions:Linezolid (600 mg once every 12 hours), teicoplanin (400 mg once every 12 hours) and daptomycin (4 mg·kg -1·d -1) can achieve satisfactory antibacterial activity for Staphylococci bloodstream infections.