Objective To explore the therapeutic mechanism of Euonymus alatus for diabetic kidney disease(DKD).Methods TCMSP,PubChem and Swiss Target Prediction databases were used to obtain the active ingredients in Euonymus alatus and their targets.GEO database and R language were used to analyze the differentially expressed genes in DKD.The therapeutic targets of DKD were obtained using GeneCards,DisGeNet,OMIM and TTD databases.The protein-protein interaction network and the"drug-component-target-disease"network were constructed for analyzing the topological properties of the core targets,which were functionally annotated using GO and KEGG pathway enrichment analyses.Molecular docking was performed for the core targets and the main pharmacologically active components,and the results were verified in db/db mice.Results Analysis of GSE96804,GSE30528 and GSE30529 datasets(including 60 DKD patients and 45 normal samples)identified 111 differentially expressed genes in DKD.Network pharmacology analysis obtained 161 intersecting genes between the target genes of Euonymus alatus and DKD,including the key core target genes SRC,EGFR,and AKT1.The core active ingredients of Euonymus alatus were quercetin,kaempferol,diosmetin,and naringenin,which were associated with responses to xenobiotic stimulionus and protein phosphorylation and regulated EGFR tyrosine kinase inhibitor resistance pathways.Molecular docking suggested good binding activities of the core active components of Euonymus alatus with the core targets.In db/db mouse models of DKD,treatment with Euonymus alatus obviously ameliorated kidney pathologies,significantly inhibited renal expressions of SRC,EGFR and AKT1,and delayed the progression of DKD.Conclusion Euonymus alatus contains multiple active ingredients such as quercetin,kakaferol,diosmetin,naringenin,which regulate the expressions of SRC,EGFR,and AKT1 to affect the EGFR tyrosine kinase inhibitor resistance signaling pathway to delay the progression of DKD.

Objective To explore the therapeutic mechanism of Euonymus alatus for diabetic kidney disease(DKD).Methods TCMSP,PubChem and Swiss Target Prediction databases were used to obtain the active ingredients in Euonymus alatus and their targets.GEO database and R language were used to analyze the differentially expressed genes in DKD.The therapeutic targets of DKD were obtained using GeneCards,DisGeNet,OMIM and TTD databases.The protein-protein interaction network and the"drug-component-target-disease"network were constructed for analyzing the topological properties of the core targets,which were functionally annotated using GO and KEGG pathway enrichment analyses.Molecular docking was performed for the core targets and the main pharmacologically active components,and the results were verified in db/db mice.Results Analysis of GSE96804,GSE30528 and GSE30529 datasets(including 60 DKD patients and 45 normal samples)identified 111 differentially expressed genes in DKD.Network pharmacology analysis obtained 161 intersecting genes between the target genes of Euonymus alatus and DKD,including the key core target genes SRC,EGFR,and AKT1.The core active ingredients of Euonymus alatus were quercetin,kaempferol,diosmetin,and naringenin,which were associated with responses to xenobiotic stimulionus and protein phosphorylation and regulated EGFR tyrosine kinase inhibitor resistance pathways.Molecular docking suggested good binding activities of the core active components of Euonymus alatus with the core targets.In db/db mouse models of DKD,treatment with Euonymus alatus obviously ameliorated kidney pathologies,significantly inhibited renal expressions of SRC,EGFR and AKT1,and delayed the progression of DKD.Conclusion Euonymus alatus contains multiple active ingredients such as quercetin,kakaferol,diosmetin,naringenin,which regulate the expressions of SRC,EGFR,and AKT1 to affect the EGFR tyrosine kinase inhibitor resistance signaling pathway to delay the progression of DKD.

Objective： ：To investigatetheeffectofsalidroside(SAL)onthephenotype of dendritic cells (DCs) and the antitumor ability of cytotoxic T lymphocytes (CTL). Methods： ：Lewis lung cancer cell line 3LL, wild type (WT) C57BL/6 mice and TLR4-/- C57BL/6 mice were chosen for this study. Mice bone marrow derived DC precursor cells were obtained to differentiate into immature DCs, which were harvested on the sixth day of culture. CD11c+ DCs were obtained by magnetic beads screening, and further divided into PBS group, SAL group and lipopolysaccharide (LPS) group.After being cultured for 48 h, the effects of SAL on surface molecules and phagocytosis of DCs as well as the efffect of TLR4 pathway on the killing effect of T cells were detected by Fow cytometry. Results： ： Compared with PBS group, expressions of DC surface molecules CD80, CD86 and MHC Ⅱ significantly increased (all P<0.05), phagocytosis significantly decreased (P<0.05), and TLR4 expression level significantly increased (P<0.01) in SAL group; Compared with WT group, after being treated with SAL or LPS, the expressions of DC surface molecules CD80, CD86 and MHC Ⅱ decreased significantly in TLR4-/- group (all P<0.05); ComparedwithPBSgroup,theactivatedCTLinSALgroupexhibited a significantly elevated killing effect against lung cancer 3LLcells (P<0.05). Conclusion：SAL can induce DC maturation by regulating TLR4, thus improving the killing ability of T cells.

Objective To investigate the association between serum 25(OH) D levels and the inci-dence of early-onset sepsis(EOS) in the very low birth weight infants(VLBWI) and the gestational age be-low 34 weeks. Methods The cord blood of 159 VLBWI were collected between January and December 2017,including 31 clinically diagnosed EOS and 128 non-EOS patients. Serum 25(OH)D<10 ng/ml was de-fined as severe vitamin D deficiency,25(OH)D 10 to 20 ng/ml as vitamin D deficiency,25(OH)D 20 to 30 ng/ml as vitamin D insufficiency and 25(OH)D >30 ng/ml as vitamin D sufficiency. Results There were no differences in gender,gestational age,birth weight and Apgar score between the EOS group and the non-EOS group(P>0. 05). Serum 25(OH) D was(9. 08 ± 4. 21) ng/ml in the EOS group and(11. 91 ± 5. 37) ng/ml in the non-EOS group(P＝0. 007). The rate of severe vitamin D deficiency was 67. 7%(21/31)in the EOS group and 41. 4%(53/128) in the non-EOS group. The rate of vitamin D deficiency was 32. 3%(10/31)in the EOS group and 52. 3%(67/128)in the non-EOS group. But there was no difference of vitamin D deficiency distribution in the two groups(P＝0. 152). The cut-off value of serum 25(OH)D level in predic-ting EOS was 10. 06 ng/ml. Conclusion The incidence of vitamin D deficiency is as high as 95%,calling for urgent attention on vitamin D supplementation in those VLBWI. Low 25(OH)D level( <10 ng/ml)might be predictive of EOS.

MicroRNA-132 (miR-132), a small RNA that regulates gene expression, is known to promote neurogenesis in the embryonic nervous system and adult brain. Although exposure to psychoactive substances can increase miR-132 expression in cultured neural stem cells (NSCs) and the adult brain of rodents, little is known about its role in opioid addiction. So, we set out to determine the effect of miR-132 on differentiation of the NSCs and whether this effect is involved in opioid addiction using the rat morphine self-administration (MSA) model. We found that miR-132 overexpression enhanced the differentiation of NSCs in vivo and in vitro. Similarly, specific overexpression of miR-132 in NSCs of the adult hippocampal dentate gyrus (DG) during the acquisition stage of MSA potentiated morphine-seeking behavior. These findings indicate that miR-132 is involved in opioid addiction, probably by promoting the differentiation of NSCs in the adult DG.
Animals ; Cell Differentiation ; Cell Line, Tumor ; Dentate Gyrus ; metabolism ; Gene Expression Regulation ; Male ; MicroRNAs ; metabolism ; Neural Stem Cells ; metabolism ; Opioid-Related Disorders ; metabolism ; Rats, Sprague-Dawley

Objective To find out the expression relation between TP53 and NOTCH1,and to explore their effects in head and neck squamous cell carcinoma.Methods Obtained the differentially expressed genes data of head and neck squamous cell carcinoma from 279 samples in TCGA database.Analyzed the co-expression relation between TP53 and NOTCH1 through Pearson and Spearman method.Cbioportal was used to analyze their co-expressed genes.Establish the co-expression network of TP53 and NOTCH1 with String database.The pathway and function of co-expression network was identified through KEGG and DAVID database respectively.Results Among the 279 samples,TP53 and NOTCH1 was co-expressed in head and neck squamous cell carcinoma.(Pearson score =0.45;Spearman score =0.41) There were 182 interaction pairs of TP53 and NOTCH1 related co-expressed gene according to the String database.(Pearson and Spearman score ＞ 0.3)These genes were enriched in some pathways such as T cell receptor signaling pathway,cell cycle,cell adhesion molecules and so on.These genes were enriched in some tumor related function including immune response,regulation of transposition,regulation of apoptotic process,cell cycle,regulation of GTPase activity and so on.Conclusion TP53 and NOTCH1 was co-expressed.Through establishing co-expressed network of TP53 and NOTCH1 and bioinformatics analysis,their function and signaling pathway were explored.The data generated from this study could provide a new reference in mechanism research of head and neck squamous cell carcinoma.

Objective To explore the FOXP3-related mechanism underlying head and neck squamous cell carcinoma.Methods We used cbioportal to identify the co-expressed genes of FOXP3 in 279 samples from head and neck squamous cell carcinoma in TCGA database.We used String database to establish the co-expression network of FOXP3.The function of co-expression network was identified through DAVID database.We used miRTarBase and StarBase database to screen the microRNA,lncRNA and circRNA that regulate FOXP3.Finally,Cytoscape software was used to establish FOXP3-related ceRNA network.Results We found 950 FOXP3 related co-expressed gene.(Spearman score over 0.5) These genes were enriched in immune response including T cell,leukocyte and lymphocyte activation.CeRNA network revealed that 2 microRNAs (i.e.,miR-31-5p and miR-210-3p),42 lncRNAs (e.g.,XIST,TUG1,JRK and LINC00473) and 31 circRNAs (e.g.,ZNF223 _hsa_ circ_ 000898 and ISY1 _hsa _circ _001090) could regulate FOXP3.Conclusion We established FOXP3-related ceRNA network and identified 42 lncRNAs and 31 circRNAs that regulate FOXP3.The data generated from this study could provide a new cut point in research and treatment of head and neck squamous cell carcinoma.

Sepsis is defined as that a variety of pathogenic microorganisms(including bacteria,fungi,viruses and protozoa) invade the blood circulation,produce toxins and cause systemic infection.The early symptoms of neonatal sepsis are atypical.Neonatal sepsis is urgent and progresses quickly,especially in preterm infants,and it is easy to prone to septic shock which is life-threatening.Therefore,early identification,accurate diagnosis,and active intervention for neonatal sepsis and septic shock is essential to reduce mortality and improve prognosis.

Objective Screening the functional gene modules that can play important roles in hypopharyngeal cancer and the potential anti-cancer drugs.Methods GEO database and MeV software were employed to screen the differentially expressed genes in hypopharyngeal cancer.Using STRING database,the protein-protein interaction network was identified.MCODE plugin of Cytoscape was used to identify the functional gene modules in the network.Based on DAVID database,the functions of modules were identified.DrugBank was used to screen the potential drugs that regulate the target genes of modules.Results 1 222 differentially expressed genes including 219 interaction pairs were i-dentified in whole genome profiling(P <0.05 ).Seven functional modules were identified in the network.The results of function analysis showed the module genes were enriched in cancer development related-function ‘regulation of angiogenesis’,‘cell adhesion’,‘DNA meta-bolic process’.A total of 50 potential drugs that regulating the 5 modules were screened.Conclusion Five functional modules that regulate the progress of hypopharyngeal cancer were identified,and maybe they can promote hypopharyngeal cancer through some functions such as regulation of angiogenesis 18 up-regulated protein kinases were identified.Their kinase inhibitors may potential have a role in anti-cancer, which provides a new target point for molecular therapy of nasopharyngeal cancer.

Objective The early stage of neonatal sepsis is short of specific clinical manifestations that easy to be misdiagnosed.This study aimed to demonstrate the clinical value of combined markers[proca-icltonin(PCT)and C-reactive protein(CRP)]in the early diagnosis of neonatal hospital-acquired infections by dynamic monitoring of PCT and CRP.Methods The study included 111neonates in the 1st Neonatal Ward of Shengjing Hospital from June 2013to August 2014which were divided into three groups and retro-spectively reviewed,including 37cases of diagnosed sepsis group,42cases of clinical sepsis group,and 32ca-ses of control group(non-sepsis neonates).We measured the serum levels of PCT and CRP in two sepsis group before antibiotic administration,12h and 24h after infection,3d and 7d after infection controlled,and in the control group before antibiotic administration.Results Before antibiotic administration,serum levels of PCT and CRP were significantly higher in two sepsis groups than in the control group(P﹤0.01).In two sepsis groups,PCT reached peak at 12h after infection[(15.00±15.51)ng/ml and(17.93±13.44)ng/ml] and decreased to normal at 3d after infection controlled[(0.49±0.47)ng/ml and(0.42±0.34)ng/ml];CRP reached peak at 24h after infection[(37.53±30.29)mg/L and(32.41±29.33)mg/L]and decreased to normal at 7d after infection controlled[(5.72±2.98)mg/L and(5.06±3.07)mg/L].The optimal cut-off values were PCT﹥2ng/ml and CRP﹥10mg/L(Youden index 76.11%,59.45%),the sensitivity were 88.61%and 75.70% ;specificity were 87.5% and 83.75% ;positive predictive value were 94.59% and 95.65% ;negative predictive value were 75.68%and 46.15%.Receiver operating characteristic area under the curve were 0.964,0.887.Conclusion In early stage of sepsis,both PCT and CRP increase.The optimal cut-off values are CRP﹥10mg/L and PCT﹥2ng/ml.CRP reaches peak at 24h after infection,decrease to normal at 7d after infection controlled,while PCT reaches peak at 12h after infection,decrease to normal at 3d after infection controlled.Combined detection of PCT and CRP can improve the sensitivity and specificity of the early diagnosis of neonatal hospital-acquired infections.