Thyroid cancer is the most common malignancy in the endocrine system .In recent years ,the incidence of thyroid cancer has increased year by year ,which sparked people′s attention.With the development of thyroid cancer research ,it is found that cytokines play a key role in the occurrence and development of tumor .At present ,the cause of thyroid carcinoma and mechanism is not yet entirely clear ,however ,the occurrence of thyroid cancer is possiblely associated with the body regulating cellular immune dysfunction .Cytokines play an important role in the whole process ,in which the relationship between cytokines IFN -γ,IL-6 and thyroid carcinoma is closely related .

10.3969/j.issn.2095-4344.2013.23.010

OBJECTIVETo investigate the expression of the key marker of endoplasmic reticulum stress (ERS) IRE1 mRNA and neuronal apoptosis in the rat hippocampus after status convulsivus (SC), and the intervention effects of edaravone, a novel free radical scavenger.

METHODSSprague-Dawley (SD) rats aged 19-21 days were randomly assigned to three groups: normal control, SC and edaravone-treated SC. SC was induced in the later two groups. The two groups were subdivided into 5 groups sacrificed at 4, 12, 24, 48, and 72 hrs after SC induction. IRE1 mRNA expression in the hippocampus was detected by RT-PCR. Neuronal apoptosis was observed by TdT-mediated dUTP nick end labeling (TUNEL). The ultramicrostructural changes of neuron were observed by electron microscopy.

RESULTSIRE1 mRNA expression was obviously up-regulated 4 and 12 hrs after SC compared with the normal control group (P<0.01). IRE1 mRNA expression in the edaravone-treated SC group was notably higher than the untreated SC group 4, 12 and 24 hrs after SC and the normal control group (P<0.01). TUNEL positive cells in the hippocampus in the untreated SC group were significantly more than those in the normal control group (P<0.01). The number of TUNEL positive cells increased with the prolonged convulsion time. TUNEL positive cells in the edaravone-treated SC group were significantly reduced compared with those in the untreated SC group 12, 24, 48 and 72 hrs after SC (P<0.05 or P<0.01), but remained higher than the normal control group (P<0.05 or P<0.01). The peri-nucleus cell organ injuries were observed 4 hrs after SC and karyopycnosis and cytoplasm condensation were observed 12 hrs after SC in the SC and the edaravone-treated SC groups. The edaravone-treated SC group demonstrated less severe apoptosis than the untreated SC group.

CONCLUSIONSEdaravone may have neuroprotections against SC by an up-regulation of IRE1 expression. It might serve as an effective agent for reducing ERS in vivo.

Animals ; Antipyrine ; analogs & derivatives ; pharmacology ; therapeutic use ; Apoptosis ; drug effects ; Disease Models, Animal ; Hippocampus ; drug effects ; metabolism ; ultrastructure ; In Situ Nick-End Labeling ; Male ; Membrane Proteins ; genetics ; Neurons ; drug effects ; ultrastructure ; Protein-Serine-Threonine Kinases ; genetics ; RNA, Messenger ; analysis ; Rats ; Rats, Sprague-Dawley ; Status Epilepticus ; drug therapy ; metabolism ; pathology

OBJECTIVETo detect unilateral spatial neglect phenomenon in children with attention deficit hyperactivity disorder (ADHD) and to test the hypothesis that the phenomenon is associated with ADHD.

METHODSThirty two boys met with ADHD diagnostic criteria of DSM-IV(TM) (ADHD group) and the 32 healthy boys without ADHD as control group participated in this study. All the participants received the flowing managements. The spatially sensitive tools of the Line Bisection test and the Star Cancellation test and some general measures (non-spatial) were used to evaluate spatial attention.

RESULTS(1) The score of Line Bisection test of boys with ADHD was (-9.37 +/- 6.57), and that of the control group was (-5.46 +/- 4.69), the difference between two groups was significant (t = -2.735, P < 0.01); the difference in left side score of the Star Cancellation test was statistically significant (t = -3.78, P < 0.01) in the ADHD group versus the control group (11.44 +/- 5.55 vs. 16.34 +/- 4.82), and the left side score was also lower than the right side one (17.13 +/- 6.36), the difference was significant (t = -3.09, P < 0.01). (2) Both groups' scores of the Line Bisection test were biased to the right side of "0" value respectively (ADHD group: t = -8.064, P < 0.01; control group: t = -6.585, P < 0.01), each side of which was lower versus "expected value" "27/27" on right side (ADHD group: t = -8.78, P < 0.01; control group: t = -7.39, P < 0.01) and left side (ADHD group: t = 15.85, P < 0.01; control group: t = -12.52, P < 0.01).

CONCLUSIONSThe results suggest that left spatial neglect may be a common general phenomenon of school age boys. Compared with normal children, children with ADHD may have obvious left spatial neglect, which suggest that there be a common neurophysiologic mechanism between left spatial bias and ADHD.

Adolescent ; Attention Deficit Disorder with Hyperactivity ; psychology ; Case-Control Studies ; Child ; Humans ; Male ; Perceptual Disorders ; Space Perception

Objective: To explore the time and genotype distribution of human enterovirus (HEV) isolated from sewage in Shanghai in 2013-2014. Methods: One sewage sample each was collected from two local sewage plants located in Minhang District and Jiading District on the same day at the day 24-28 of every month from 2013 to 2014. Each sample weighed 1 L. The specimens were concentrated by anionic membrane absorption, eluted with beef extract solution, and then used to inoculate RD, HEp-2, and L20B cell lines. A total of 249 enterovirus strains were isolated from sewage samples during the study period, including 185 non-polio enterovirus (NPEV) and 64 poliovirus (PV) strains, which were identified as vaccine strains. RT-PCR and Sanger sequencing were performed to identify HEV genotypes. Homologous analysis of VP1 sequences was conducted using BioEdit (version 7.0.0). Phylogenetic analysis was performed using the neighbor-joining method based on the alignment of VP1 gene sequences using MEGA (version 4.0.2). Results: Among 185 NPEV strains, 178 strains were successfully sequenced and classified into 15 genotypes, including coxsackievirus group B (CVB) 2, 3, and 5; enteric cytopathic human orphan (ECHO) virus 1, 3, 6, 7, 11, 13, 19, 20, 24, 25, and 30; and coxsackievirus group A 4. CVB5 and ECHO6 genotypes accounted for 33.5% (56 strains) and 24.9% (43 strains) of NPEV isolates, respectively. During the study period, HEV isolates were mainly isolated in summer and autumn in Minhang District. ECHO6 strains were frequently isolated from June 2013 to July 2014. Thereafter, the number of ECHO6 strains gradually reduced in the second half of 2014. CVB5 strains demonstrated scattered distribution from 2013 to the first half of 2014 and gradually increased in the second half of 2014. The distribution of ECHO6 and CVB5 strains in Jiading District was similar to that in Minhang District. In 2013-2014, CVB5 strains comprised C6 and C8 subgenotypes, which belong to two transmission chains and show large differences compared with foreign strains isolated during the same period. ECHO6 strains comprised C6, C8, and D9 subgenotypes, which belong to three transmission chains. Moreover, ECHO6 subgenotype D9 was a dominant subgenotype in Shanghai, with broad geographical distribution both at home and abroad. Conclusion Poliovirus was identified as a vaccine strain in environmental surveillance from June 2013 to April 2014 in Shanghai. Several transmission strains of ECHO6 and CVB5 were identified, which were the dominant serotypes.

Objective:Apt-A10-3.2 (aptamer of prostate specific membrane antigen (PSMA)) can be used as a specific ligand for early diagnosis and targeted treatment of prostate cancer. Mouse double minute 2 homolog (MDM2) is closely related to the malignancy of prostate cancer, and MDM2 small interfering RNA (siRNA) can silence MDM2 gene through RNA interference. To design a novel chimera of PSMA Apt-MDM2 siRNA and combine it with docetaxel (DTX) to explore a new diagnosis and treatment model combining targeted therapy of PSMA-positive prostate cancer with 99Tc m-chimera imaging monitoring. Methods:Apt-siRNA were obtained by covalent connection of PSMA Apt-A10-3.2 and MDM2 siRNA, which was combined with DTX to treat PSMA-positive prostate cancer cell lines (22RV1 and LNCaP). Cell lines were treated with Apt-siRNA alone or in combination with DTX. The levels of MDM2 and apoptosis-related proteins (B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X (Bax), poly ADP-ribose polymerase (PARP), caspase-3) were detected by Western blot, which were used to evaluate the therapeutic effect. Fifteen BALB/c mice bearing 22RV1 xenografts were treated with PBS, DTX+ Apt-siRNA (200 pmol) and DTX+ Apt-siRNA (400 pmol), respectively. Tumor volume and MDM2 level were observed, and 99Tc m-Apt-siRNA SPECT imaging was performed to obtain the tumor/muscle (T/M) ratio. One-way analysis of variance, Tukey′s test and linear regression analysis were used for data analysis. Results:The levels of MDM2 protein were significantly decreased by Apt-siRNA (0.25±0.02, F=183.40, P<0.001; 0.56±0.03, F=37.15, P<0.001) in 22RV1 and LNCaP cells. After the treatment of Apt-siRNA+ DTX, the levels of Bcl-2 were significantly decreased, and the levels of Bax, PARP and caspase-3 were significantly increased. MDM2 protein level (400 pmol: 0.59±0.12; F=49.99, P=0.023) and tumor volume (400 pmol: (0.22±0.07) cm 3;F=71.30, P=0.039) were significantly inhibited by Apt-siRNA+ DTX in mice bearing 22RV1 xenografts. As for 99Tc m-Apt-siRNA SPECT imaging in vivo, T/M ratio of treatment group was significantly decreased (400 pmol: 2.07±0.22; F=34.99, P=0.022), and there was a linear regression relationship between T/M ratio and the expression level of MDM2 ( R2=0.875, P<0.001). Conclusion:Apt-siRNA combined with DTX can effectively inhibit the progression of prostate cancer, and realize visual targeted diagnosis and treatment of PSMA-positive prostate cancer by coupling radionuclide technetium.

Objective To investigate whether decursin(Dec) could inhibit EC109 cells proliferation by suppression of janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) signaling pathway in human esophageal squamous cell carcinoma.Methods The EC109 cells were treated with Dec(20,40,and 80 pmmol/L) for48 h.The cell viability was evaluated by MTT;the apoptotic cells was labelled by TUNEL;the mitochondrial oxidative stress level was detected by fluorescent staining;and western blotting was used to analyze the proteins of JAK2/STAT3 signaling and apoptosis in EC109 cells,respectively.After co-application of JAK2 / STAT3 antagonist(AG490),the inhibitory ability of Dec to EC109 was observed from the in vivo and in vitro levels.Results Compared to the control group,different concentrations of Dec dose-dependently down-regulated expressions of p-JAK2 [(55.89 ± 6.04) ％] and p-STAT3 [(45.27 ± 8.65) ％],repressed EC109 cell activity(0.43 ± 0.078),increased apoptotic rate[(35.31 ± 8.41)％],reduced MMP levels[(37.23 ± 6.89)％],promoted reactive oxygen species(ROS) [(231.81 ± 19.63)％],decreased glutathione (GSH) activity [(46.78 ± 6.91)％,P＜0.05].However,Dec did not significantly affect the activity of the normal esophageal epithelium HET-1A cells(P ＞0.05).Meanwhile,Dec obviously leaded to reduction of Bcl2,increment of Bax,and augment of Caspase-3 cleavage (P ＜0.05).Additionally,the inhibitory effect of Dec on EC109 was specifically intensified after co-application of AG490 in vivo and in vitro levels(P ＜0.05).Conclusion Dec can fight against human esophageal squamous cell carcinoma in vitro and in vivo via activation of mitochondrial oxidative stress-induced apoptosis which was mediated by JAK2/STAT3 pathway.

Female ; Humans ; Male ; Diabetes Mellitus, Type 2/genetics* ; Genetic Predisposition to Disease/genetics* ; Postmenopause ; Risk Factors ; Sex Hormone-Binding Globulin/genetics* ; Testosterone

Background::Prenatal and postnatal factors may have joint effects on cardiovascular health, and we aimed to assess the joint association of birth weight and ideal cardiovascular health metrics (ICVHMs) prospectively in adulthood with incident cardiovascular disease (CVD).Methods::In the UK Biobank, 227,833 participants with data on ICVHM components and birth weight and without CVD at baseline were included. The ICVHMs included smoking, body mass index, physical activity, diet information, total cholesterol, blood pressure, and hemoglobin A1c. The Cox proportional hazards model was used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) in men and women.Results::Over a median follow-up period of 13.0 years (2,831,236 person-years), we documented 17,477 patients with incident CVD. Compared with participants with birth weights of 2.5-4.0 kg, the HRs (95% CIs) of CVD among those with low birth weights was 1.08 (1.00-1.16) in men and 1.23 (1.16-1.31) in women. The association between having a birth weight <2.5 kg and CVD risk in men was more prominent for those aged <50 years than for those of older age ( P for interaction = 0.026). Lower birth weight and non-ideal cardiovascular health metrics were jointly related to an increased risk of CVD. Participants with birth weights <2.5 kg and ICVHMs score 0-1 had the highest risk of incident CVD (HR [95% CI]: 3.93 [3.01-5.13] in men; 4.24 [3.33-5.40] in women). The joint effect (HR [95% CI]: 1.36 [1.17-1.58]) could be decomposed into 24.7% (95% CI: 15.0%-34.4%) for a lower birth weight, 64.7% (95% CI: 56.7%-72.6%) for a lower ICVHM score, and 10.6% (95% CI: 2.7%-18.6%) for their additive interaction in women. Conclusions::Birth weight and ICVHMs were jointly related to CVD risk. Attaining a normal birth weight and ideal ICVHMs may reduce the risk of CVD, and a simultaneous improvement of both prenatal and postnatal factors could further prevent additional cases in women.

ObjectiveTo analyze the genetic characteristics of the hemagglutinin （H） gene of measles virus （MeV） in Shanghai， 2001‒2018. MethodsNasopharyngeal swab specimens were collected from suspected measles cases reported in Shanghai from 2001 to 2018， and the isolation of measles virus was conducted with Vero/hSLAM cell line. RT-PCR amplification and sequencing were conducted after RNA extraction to analyze the genetic characteristics of the complete H gene. ResultsIn total， 5 665 nasopharyngeal swab samples were collected by suspected measles case surveillance from 2001 to 2018， and 1 394 measles virus strains were isolated. The homology of nucleotide acid and amino acid among 349 representative measles virus isolates was 87.4%‒100.0% and 85.1%‒100.0%， respectively. The homology of nucleotide acid and amino acid between representative measles virus isolates and China vaccine strain （S191） was 85.7%‒100.0% and 84.1%‒100.0%， respectively. All the sub-genotype H1a MeV isolates had an amino acid substitution （Ser240Asn）， which removed a predicted N-linked glycosylation site. ConclusionMost of the MeV isolates are sub-genotype H1a analyzed based on H gene， which are identical to those of the N gene. The predicted amino acid sequences of the H protein are relatively conserved at most of the functionally significant amino acid positions.