To investigate the correlation of polymorphisms at the rs1837253 and rs3806933 loci of the thymic stromal lymphopoietin(TSLP)gene with asthma susceptibility and Eos,IgE,and FeNO levels in children.A total of 143 asthmatic children were selected as the study group,and 112 healthy children undergoing routine health examinations at the same hospital were chosen as the control group.The MassARRAY SNP genotyping technology was used to detect the genotypes at two loci,while serum IgE levels were determined by using the turbidimetric scattering method.The distribution differences in genotype and allele frequencies between the two groups were analyzed,along with the effects of different genotypes on Eos,IgE,and FeNO levels.There was no statistically significant difference in the distribution of rs1837253 allele and genotype frequencies as well as rs3806933 allele frequencies between the two groups(P＞0.05).However,asthma group rs3806933 CT genotype frequency was higher than the control group,and CC genotype frequency was lower than the control group(P＜0.05).Compared with the wild-type genotypes,children who carried rs1837253 CT+CC and rs3806933 CT,CT+TT genotypes had an increased risk of asthma(CT+CC vs TT:OR=2.737,95%CI:1.514-4.945;CT vs CC:OR=2.058,95%CI:1.194-3.543;CT+TT vs CC:OR=1.843,95%CI:1.109-3.062).There was an overall statistical difference in Eos counts among the three genotypes at the rs1837253 locus in the asthma group(P＜0.05,correction for multiple comparisons P＞0.05),but not in the control group(P＞0.05).There were no statistically significant differences in Eos%,IgE,and FeNO levels among the genotypes at the two loci and no significant difference in Eos counts among genotypes at the rs3806933 loci(P＞0.05).Taken together,polymorphisms at rs1837253 and rs3806933 loci in the promoter region of the TSLP gene are associated with asthma susceptibility in children.rs3806933 CT genotype may serve as a potential genetic marker for asthma,and rs1837253 CT+CC and rs3806933 CT+TT genotypes are risk factors for asthma in children;the rs1837253 locus polymorphism tended to affect blood Eos counts,while the two SNPs were not associated with Eos%,serum IgE,and FeNO levels.

Long noncoding RNAs (lncRNAs) play a crucial regulatory role in the development and progression of multiple cancers. However, the potential mechanism by which lncRNAs affect the recurrence and metastasis of ovarian cancer remains unclear. In the current study, the lncRNA LOC646029 was markedly downregulated in metastatic ovarian tumors compared with primary tumors. Gain- and loss-of-function assays demonstrated that LOC646029 inhibits the proliferation, invasiveness, and metastasis of ovarian cancer cells in vivo and in vitro. Moreover, the downregulation of LOC646029 in metastatic ovarian tumors was strongly correlated with poor prognosis. Mechanistically, LOC646029 served as a miR-627-3p sponge to promote the expression of Sprouty-related EVH1 domain-containing protein 1, which is necessary for suppressing tumor metastasis and inhibiting KRAS signaling. Collectively, our results demonstrated that LOC646029 is involved in the progression and metastasis of ovarian cancer, which may be a potential prognostic biomarker.
Humans ; Female ; MicroRNAs/metabolism* ; RNA, Long Noncoding/metabolism* ; RNA, Competitive Endogenous ; Cell Line, Tumor ; Ovarian Neoplasms/genetics* ; Cell Proliferation/genetics* ; Gene Expression Regulation, Neoplastic ; Cell Movement/genetics* ; Adaptor Proteins, Signal Transducing/metabolism*

ObjectiveTo establish an ischemia-reperfusion model in cynomolgus macaques and to analyse the effects of edaravone intervention. MethodsA total of fifteen adult male cynomolgus macaques were randomly divided into three groups: sham operation (Sham group, n=3), ischemia-reperfusion model (Model group, n=6) and edaravone treatment (Edaravone group, n=6). Ischemic-reperfusion model of cynomolgus macaques was established by clamping the M1 branch of the left cerebral artery for 1 h. After 2 h of reperfusion, the animals in Edaravone group were injected with 0.5 mg/kg edaravone intravenously for intervention treatment, while the animals in Sham and Model groups were injected with an equal volume of normal saline intravenously, twice a day, from the 2nd to 7th day. The behavioral video recordings, clinical observations and neurological deficit scores of cynomolgus macaques were obtained, and brain edema volume and cerebral ischemia volume were statistically analyzed. ResultsCompared with the Sham group, the animals in Model group showed typical symptoms of ischemic stroke, with a significant increase in the neurological deficit score， the volumes of edema and infarct of brain tissue (all P＜0.01). Compared with Model group, the neurological deficit score, the volumes of edema and infarct of brain tissue were significantly reduced in Edaravone group (all P＜0.05). ConclusionAn animal model of ischemia-reperfusion in cynomolgus macaques was successfully established, and edaravone was confirmed to alleviate the damage caused by ischemia-reperfusion.

Objective To investigate the relationship of extracellular regulated protein kinases activation and neural cells autophagy in rats after subarachnoid hemorrhage.Methods One hundred twenty male SD rats were randomly divided into sham operated group,SAH group,ERK1/2 inhibitor U0126 group,autophagy inducer rapamycin (Rap) group.The animal models were established by injecting the autologous blood into cisterna magna twice.U0126 (5μ g/μL) and Rap (10nmol/μL) were injected into lateral ventricles in U0126 group and Rap group 30min before SAH.The morphology of hippocampal nerve cells were examined by using light microscopy.The expression levels of phosphorylated ERK 1/2 (p-ERK 1/2),ERK 1/2mRNA and autophagy markers (Beclin-1 and Beclin-1 mRNA、LC3-Ⅱ and LC3mRNA) in the hippocampus were detected by using inmunohistochemistry and real-time fluorescence quantitative PCR.Result Compared with sham group,the rate of dead nerve cells,the mRNA levels of ERK1/2,Beclin-1 and LC3 as well as the levels of the p-ERK1/2,Beclin-1 and LC3-Ⅱ increased in SAH group (P＜0.05).Compared with SAH group,the rate of dead nerve cells increased(P＜0.05),the ERK1/2 mRNA,Beclin-1 mRNA and LC3 mRN A,and p-ERK1/2,Beclin-landLC3-Ⅱ in U0126 group decreased(P＜0.05);the rate of dead nerve cells decreased (P＜0.05),the Beclin-1 mRNA and LC3 mRNA,the Beclin-1and LC3-Ⅱ level increased in Rap group(P＜0.05),but ERK 1/2 mRNA and p-ERK 1/2 remained unchanged (P＞0.05).Conclusion Activation of the ERK1/2 signaling pathway after SAH,can induce nerve cells death by increasing Beclin-1 and LC3-Ⅱ expressions.

Objective To investigate the effect of MAPK activation on autophagy in the hippocampus of rats with subarachnoid hemorrhage.Methods A total of 100 male SD rats were divided into 5 groups randomly:sham operated group,SAH group,inhibitor U0126 group,inhibitor SB203580 group,SP600125 group.The animal model was established by injecting the autologous blood into cisterna magna twice.The morphological changes of hippocampus nerve cells of rat brain were detected with HE.The mRNA levels of ERK1/2,p38MAPK,JNK and LC3 in hippocampus were detected with quantitative real time PCR and the expression of phosphorylated ERK1/2,phosphorylated p38MAPK,phosphorylated JNK and LC3-Ⅱ in hippocampus of rat brain were detected by immunohistochemistry.Results Compared with the Sham group,the survival rate of neurons in SAH group decreased (6 h:(84.982 ± 5.723) ％,24 h:(74.383± 9.860) ％,48 h:(62.860± 10.820) ％,72 h:(52.260± 10.960) ％) (all P＜0.05).The levels of ERK1/2 mRNA,p38MAPK mRNA,JNK mRNA and LC3 mRNA in hippocampus increased (all P＜ 0.05) and the expression of p-ERK1/2,p-p38MAPK,p-JNK,LC3-Ⅱ proteins increased(all P＜0.05).Compared with the SAH group,the survival rate of neurons in U0126 group was decreased (6 h:(71.620±6.542) ％,24 h:(66.221±7.742)％,48 h:(55.208±8.802) ％,72 h:(46.242±7.782) ％),and the ERK1/2 and LC3 in hippocampus decreased both in mRNA level and in protein level(all P＜0.05).Compared with the SAH group,the survival rate of neurons in SB203580 groups was increased (6 h:(89.082±6.602)％,24 h:(85.840±9.726) ％,48 h:(74.96± 10.916) ％,72 h:(69.211 ± 10.745) ％),and the p38MAPK,LC3-Ⅱ in hippocampus decreased at both mRNA and protein levels (all P＜0.05).Compared with the SAH group,the survival rate of neurons in SP600125 groups was increased (6 h:(91.620± 7.542) ％,24 h:(86.221 ± 10.742) ％,48 h:(75.208±11.802) ％,72 h:(70.242± 11.782) ％).The expression of JNK was decreased while the LC3-Ⅱ was increased in hippocampus (P＜0.05).Conclusion MAPK activation is involved in the autophagy of hippocampal neurons after SAH,in which ERK1/2 activation plays a positive role in the regulation of autophagy in hippocampal neurons after SAH,while p38MAPK and JNK activation plays a negative role in autophagy.

Objective To establish reference values for blood pressure in cynomolgus monkeys in different ages.Methods The blood pressures and blood lipids indexes were detected in 521 cynomolgus monkeys using an American BECKMAN-CX4 automatic biochemical analyzer and a wrist electronic blood pressure monitor.Statistical tests were performed to analyze the data.Results Significant differences were found in blood pressure values of cynomolgus monkeys in different ages.Blood pressure values in the elderly group were higher than those of other groups.The morbidity of hypertension in the elderly group was higher than those of the other groups.Body mass index (BMI) in the hypertension group was higher than that of normal group in the same age.The incidence of hypertension in the elderly group with hyperlipemia was higher than that of other groups.Logistic regression analysis showed that age, BMI and hyperlipidemia in the hypertensive group were 1.435, 1.218, and 2.337 times higher than those of the normal group when predicting the risk of hypertension.Conclusions We have initially established reference values of blood pressure in cynomolgus monkeys in different ages.Age, BMI and hyperlipidemia are risk factors of spontaneous hypertension in cynomolgus monkeys, and the measurement of blood pressure may provide a basis for the screening of cynomolgus monkey model of spontaneous hypertensive and related research.

According to the phenomenon that the curriculum of psychological health education for college students is theoretical,lack of experience and the teaching form is single,this research attempts to private a blended teaching which is based on the small private online course (SPOC) and experiential teaching.The content of mental health is divided into theoretical knowledge and experience knowledge.And the theoretical knowledge is taught through online teaching in the form of massive open online courses (MOOC),while the experiential knowledge is taught by pure experiential teaching in the classroom.The study has summed up 3 stages of learning mode:learning before class,teaching experience and reflection after class.This changes the single classroom theory teaching to students experience learning.Besides,formative evaluation is used as assessment methods,which has enhanced the effectiveness of the course and at the same time,it has also promoted the improvement of teachers' teaching level effectively.

Objective To observe the effect of aerobic exercise preconditioning on growth-associated protein-43 (GAP-43) and Nogo-A in rats after cerebral ischemia/reperfusion. Methods Sprague-Dawley rats were equally divided into sham group (n=40), cerebral ischemia/reperfusion group (n=40) and aerobic exercise preconditioning group (n=40), and global cerebral ischemia model was formed with modified four-vessel occlusion. The rats was sacrificed six hours, one day, three days and seven days after ischemia, respectively. The hippocampus neural cells were observed in five rats with HE staining and immunohistochemistry of GAP-43 and Nogo-A, and the other five rats were test-ed with RT-PCR of GAP-43 and Nogo-A. Results Compared with those in the cerebral ischemia/reperfusion group, the apoptotic neurons and expression of GAP-43 significantly increased all the time points in the aerobic exercise preconditioning group (P<0.01), while the ex-pression of Nogo-A decreased (P<0.01). Conclusion Aerobic exercise preconditioning can promote the regeneration of neuronal cells and axon after cerebral ischemia/reperfusion injury, which is related to the regulation of GAP-43 and Nogo-A.

Objective To observe the effect of exhaustive exercise preconditioning on GAP?43 and Nogo?A in rats with cerebral ischemia reperfusion. Methods 90 rats were randomly divided into sham oper?ation group,group of cerebral ischemia reperfusion(I/R) and exhaustive exercise preconditioning group.Rats were sacrificed at 6 h,1 d,3 d and 7 d respectively after injury. Neural functions were detected by shuttle box. Morphological changes of hippocampal neural cells were observed by HE staining. Expressions of GAP?43 and Nogo?A were detected respectively by immunohistochemistry and RT?PCR technology. Re?sults Compared with the sham group,the death rate of apoptotic neurons in I/R group was decreased( 6 h:(30.97±2.09)%,1 d:(38.41±1.10)%,3 d:(46.81±2.04)%,1 d:(43.46±1.57)%),the index of learning and memory ability(AARR?7 d:(38.00±12.60)%,PAL?7 d:(27.90±1.79)s) and expression of GAP?43 were decreased(6 h:(2.89±0.85),1 d:(4.06±0.25),3 d:(4.78±0.98),7 d:(7.02±0.21)),the expression of Nogo?A was increased(6 h:(2.93±0.19),1 d:(5.47±0.32),3 d:(4.62±0.26),7 d:(4.12±1.11))(P<0.05).Compared with I/R group,the death rate of apoptotic neurons in exhaustive exercise preconditioning group were decreased,the index of learning and memory ability(AARR?7 d:(20.66±7.60)%,PAL?7 d:(35.53±2.41)s) and expression of GAP?43 were decreased(6 h:(2.03±0.14),1 d:(2.92±0.27),3 d:(3.35±0.34),7 d:(5.24±0.52)),the expression of Nogo?A were increased(6 h:(3.92±0.51),1 d:(6.90± 0.79),3 d:(5.87±0.48),7 d:(5.37±0.50))(P<0.05). Conclusion Exhaustive exercise preconditioning ag? gravates the injury of neurons and neural function,which is related to the regulation of GAP?43 and Nogo?A in the hippocampus of rats.

This article was aimed to study the proteomic spectra expression of traditional Chinese medicine (TCM) cold and heat constitution rats with two-dimensional gel electrophoresis (2-DE), in order to search for the cold and heat-associated proteins for the investigation of the biological basis of TCM cold and heat body constitution formation. The total protein in rat’s liver cell was extracted. The 2-DE and MALDI-TOF/TOF mass spectrometry (MS) were used in the screening and identification of differentially expressed proteins of cold and heat constitution rats. The results showed that a total of 10 different points in the protein expression were obtained with statistical significance after screening and MS, which were carbamoyl-phosphate synthase, protein disulfide isomerase associated 3, catalase, hydroperoxide isomerase, cytosol aminopeptidase, glutamate dehydrogenase 1, 3-hydroxy-3-methylglutaryl-coenzyme A synthase 2, heat shock protein 60 (Hsp60) precursor, homocysteine, 78 kDa glucose-regulated protein precursor. It was concluded that some differences were existed in the proteomic spectra expression of TCM cold and heat constitution rats. The abnormality of enzyme protein metabolism may be one of the material bases for the formation of cold and heat constitution.