Objective To analyze the genome-wide profiles of H3K9 crotonylation(H3K9cr)in mouse embryonic stem cells(mESCs)in normal or deficient folic acid(FA)by chromatin immunoprecipitation sequencing(ChIP-seq)in order to observe the genome-wide changes in H3K9cr status and the regulated pathway genes under FA deficiency condition.Methods The mESCs were divided into normal FA group(4 mg/L,FA4)and FA deficient group(0 mg/L,FAO).Western blotting and immunohistochemical(IHC)assay were used to detect the protein level of H3K9cr in the FA deficient mESCs and the embryonic brain tissues of neural tube defects(NTDs)mice,respectively.ChIP-seq technology was carried out for sequence identification of the obtained specific binding DNA fragments.Differentially expressed genes(DEGs)were analyzed and visualized by gene ontology(GO)and Kyoto encyclopedia of genes and genomes(KEGG)pathways,with the aim of analyzing the whole genome of mESCs with FA deficiency and validating the regulated genes.Results Overall H3K9cr level was significantly lower in the FA deficient mESCs and the embryonic brain tissues of NTDs mice than in the corresponding normal FA mESCs and mice(P＜0.05).Neurodevelopmental-related genes such as Bdnf,Pax6,and App were down-regulated in the FA deficient mESCs(P＜0.05).The KEGG pathway analysis indicated that the DEGs were concentrated in axon-guiding,neuroactive ligand-receptor interaction,glutaminergic synapses and other nervous system-related pathways.Conclusion FA deficiency in embryonic stem cells participates in the regulation of neurodevelopmental genes through modification of H3K9cr,suggesting that the modification of histone crotonylation may be involved in neurodevelopmental diseases induced by FA deficiency.

Objective:To study the therapeutic effect Tetrandrine (TET) on striatal injury caused by microwave radiation and underlying mechanism.Methods:C57BL/6N mice were randomly divided into blank control group (C), radiation control group (R), TET group (TET) and TET combined with radiation group (TET+ R). The mice of radiation group were exposed to 2.856 GHz 8 mW/cm2 microwave on whole-body for 15 min. TET (60 mg/kg) was injected intraperitoneally once a day for 3 consecutive days. The TET structure was verified by ultraviolet spectrophotometry. The open field experiment was used to detect the change of anxiety in mice. Histopathological and ultrastructural changes of the striatum were observed by light microscopy and transmission electron microscopy (TMT). Quantitative real-time PCR (qPCR) was used to detect gene expression changes of voltage-gated calcium channel (VGCC) subtype in the striatum.Results:The open field experiments showed that the time and distance of mice to explore the central region after microwave radiation were significantly lower than that before radiation ( t=4.60, 5.18, P<0.01), and the TET administration significantly improved these changes ( F=1.43, 4.37, P < 0.05). 7 d after microwave radiation, some neuronal nuclei in the striatum of mice contracted and could be stained deeply, which was more obvious in the globus pallidus area. The partial neuronal apoptosis, swelling and cavitation of glial cell mitochondria, blurring of synaptic gaps, and widening of perivascular gaps in the striatum were observed by TMT. The above lesions were significantly rescued after TET administration. But both microwave radiation and TET administration had no significant effect on the gene expressions of striatal VGCC ( P > 0.05). Conclusions:TET has a therapeutic effect on anxiety-like behavior and structural damage of striatum caused by microwave radiation, which is independent of the expression of striatal VGCC genes.

Objective:Through the analysis of the evaluation index system of the major rankings of universities and hospitals, this paper aims to provide a reference for the discipline construction of affiliated hospitals in universities.Methods:This paper comprehensively analyzes and compares the evaluation objectives and indicators of the five major rankings of universities and the three major rankings of hospitals in China and abroad.Results:Each main rankings have its own characteristics that both positive and with possible limitations.Conclusions:Hospital management departments can refer certain indicators in order to identify possible gaps of the hospital discipline development. Also, tailored corresponding measurements for discipline development can be developed in combination with real-needs.

AIM: To study the protective effect and mechanism of rosuvastatin on cerebral ischemia-reperfusion injury. METHODS: (1) Cerebral infarction and OGD/R cell models were established to detect the effects of different concentrations of rosuvastatin on cell proliferation and apoptosis; (2) Different concentrations of rosuvastatin were used to treat OGD/R cell models and to observe rosuvastatin effects on cell morphology and expression and localization of UCP2-SIRT3 in cells; (3) UCP2 silent cell line was constructed to observe cell mitochondrial morphology and expression and localization of TOMM20 and SIRT3 molecules in cells, and to study the channels and mechanisms that play a protective role of rosuvastatin in OGD/R cell model; (4) The mitochondrial membrane potential, mitochondrial gene PGC1, Drp1 and Opa1 expression were detected to study the protective effect of rosuvastatin on mitochondria. RESULTS: (1) Rosuvastatin of different concentrations could significantly reduce OGD/R cell apoptosis and increase cell survival rate; (2) Rosuvastatin exerted cell protection by affecting the expression of UCP2 and SIRT3 in cells, thereby protecting cells from OGD/R injury; (3) Rosuvastatin affected the expression of TOMM20 by regulating UCP2, increased mitochondrial transmembrane transport and energy metabolism, enhanced mitochondrial function, and improved cell state and reduced apoptosis. CONCLUSION: Rosuvastatin inhibits mitochondrial damage of OGD/R cells by regulating UCP2/SIRT pathway, thereby exerting neuron protection.

Objective:To investigate the effect of P2X4R silencing on 6-hydroxydopamine (6-OHDA) induced Parkinson's disease (PD) cell model and its mechanism. Methods:(1) According to the 6-OHDA concentrations, the SH-SY5Y cells were divided into 0 μmol/L 6-OHDA group, 50 μmol/L 6-OHDA group, 100 μmol/L 6-OHDA group, and 150 μmol/L 6-OHDA group. CCK-8 was used to detect the cell survival rate, Western blotting was used to detect the P2X4R protein expression, and real time quantitative RT-PCR was used to detect the P2X4R mRNA expression. The optimal concentration of 6-OHDA was selected to induce PD cell model. (2) SH-SY5Y cells at logarithmic phase were transfected with P2X4R siRNA lentiviral plasmids of different sequences (P2X4R-siRNA540, P2X4R-siRNA792, and P2X4R-siRNA1401) and nonsense sequence normal control plasmid (NC-siRNA), respectively (P2X4R-siRNA540 group, P2X4R-siRNA792 group, P2X4R-siRNA1401 group, and NC-siRNA group); the P2X4R mRNA and protein expressions were detected by real time quantitative RT-PCR and Western blotting, and the P2X4R siRNA sequence with the best silencing effect was screened to establish P2X4R silencing cell line. (3) The PD cells induced by the optimal concentration of 6-OHDA were transfected by P2X4R-siRNA enjoying the best silencing effect, NC-siRNA, and P2X4R antagonist CORM-2 (PD+P2X4R-siRNA group, PD+NC-siRNA group, and PD+CORM-2 group); CCK-8 and flow cytometry were used to detect the survival rate and apoptosis rate of cells in each group, and Western blotting was used to detect the protein expressions of connexin (PANX1), toll-like receptor (TLR)-2, Caspase-3 and cleaved Caspase-3. (4) The PANX1 or TLR-2 over-expression plasmids (pCMV3-PANX1 and pCMV3-TLR2), and negative control plasmid (pCMV3-NCV) were transfected into cells from the PD+P2X4R-siRNA group (PD+P2X4R-siRNA+pCMV3-PANX1 group, PD+P2X4R-siRNA+pCMV3-TLR2 group, and PD+P2X4R-siRNA+pCMV3-NCV group); CCK-8 and flow cytometry were used to detect the survival rate and apoptosis rate of cells in each group; Western blotting was used to detect the TLR-2, Caspase-3 and cleaved Caspase-3 protein expressions. Results:(1) As compared with that in the 0 μmol/L 6-OHDA group, the cell survival rate in 50, 100, and 150 μmol/L 6-OHDA groups was significantly decreased in a dose-dependent manner, and the P2X4R protein and mRNA expression levels were significantly increased in a dose-dependent manner ( P<0.05); among them, 100 mol/L 6-OHDA was the most suitable concentration to induce PD cell model. (2) As compared with those in the NC-siRNA group, the P2X4R mRNA and protein expressions in P2X4R-siRNA540 group, P2X4R-siRNA792 group, and P2X4R-siRNA1401 group were significantly decreased ( P<0.05); P2X4R mRNA and protein expressions were the lowest in the P2X4R-siRNA540 group. (3) As compared with PD+NC-siRNA group, the PD+P2X4R-siRNA group and PD+CORM-2 group had significantly increased survival rate, significantly decreased apoptosis rate, and statistically decreased Caspase-3, cleaved Caspase-3, PANX1 and TLR-2 protein expression levels ( P<0.05). (4) As compared with PD+P2X4R-siRNA+pCMV3-NCV group, the TLR2 protein expression in PD+P2X4R-siRNA+pCMV3-PANX1 group was significantly lower ( P<0.05); as compared with PD+P2X4R-siRNA+pCMV3-NCV group, PD+P2X4R-siRNA+pCMV3-TLR2 group had significantly increased cell survival rate, significantly decreased apoptosis rate, and significantly decreased Caspase-3 and cleaved Caspase-3 protein expressions ( P<0.05). Conclusion:P2X4R silencing can significantly improve the survival rate of PD cell model induced by 6-OHDA, reduce apoptosis and expressions of apoptosis related proteins (Caspase-3 and cleaved Caspase-3), and play a neuroprotective role, whose mechanism may be related to PANX1/TLR-2 signal pathway.

Objective ToevaluatethevalueofMRDKIandDWIindiagnosingendometrialcarcinomaandevaluatingitspathologicalgrade. Methods TheDKIandDWIdataof48patientswithendometrialcarcinomaand27patientswithnormalendometrium wereanalyzed retrospectively.Thevaluesofmeankurtosis (MK),meandiffusion (MD)andADCinendometrialcarcinomaandnormalendometrium were measuredrespectively.Thesimilaritiesanddifferencesoftheparametersbetweentheendometrialnormalgroup(G0)andtheendometrialcarcinoma group (G1,G2,G3)werecomparedandanalyzed.TheROCcurvewasemployedtoevaluatethediagnosticefficacyandthresholdof eachparameter.P earson correlation wasappliedtoanalyzethecorrelationbetweeneachparametervalueandpathologicalgrade.Results The MK valuesincreasedgradually,meanwhiletheMDandADCvaluesdecreasedgraduallyinG0,G1,G2andG3groups.ExceptforMDand ADCvaluesbetweenG0andG1groups,othervalueswerestatisticallysignificantdifferent(P<0.05)betweendifferentgroups.In differentiatingoftheG0/(G1+G2+G3),G0/G1,G1/G2,G2/G3,theMKvalueshadthehighestdiagnosticefficacy(AUC=09.2,07.6,09.0,0.96, P<0 .05 ).M oreover ,in the correlation of pathological grading ,M K>M D>A D C (r=0 .850 ,0 .781 ,0 .709 ,P<0 .05 ).Conclusion Both DKIandDWIcandiagnoseandevaluatepathologicalgradeofendometrialcarcinoma.ComparedwithDWI,DKIembracesmoreperfectmathematical modelandmoresensitiveparameters,andcanbeusedasaneffectivemethodtoevaluatethepathophysiologicalfeaturesofendometrialcarcinoma.

Objective This paper aimed to discuss the construction strategy to promote research integrity in medical science from the perspective of hospital research administrators,and to provide theoretical basis for fulfilling the national strategic requirement of implementing "Scientific research integrity construction ".Methods Analyze and summarize the connotation,manifestations,causes and countermeasures of research integrity and research misconduct.Results The misconduct in medical scientific research occurred in various aspects,including scientific research projects,research papers,scientific achievements and other different stages.Behind reasons include weak sense of research integrity,lack of moral integrity education and training,improper academic evaluation system,lack of sound supervision,reward and punishment mechanism,etc.Conclusions A lot of strategies could adopted to promote the construction of research integrity and development of medical scientific research,for instance,strengthening scientific research integrity education,establishing a multi-dimensional evaluation system,improving the supervision,reward and punishment mechanism of scientific research integrity,as well as promote a better scientific research atmosphere.

This study aimed to investigate the effects of fusion proteins GnRH-GRP(G3G6)and HSP65-STEAP1(HST1)on dendritic cells(DC)and the sensitization of DCs to B16F10 melanoma. The fusion proteins G3G6 and HST1 were obtained using the previous engineering strains in our laboratory. Group by unsensitized DC(US-DC), the G3G6 fusion protein sensitized DC, the HST1 fusion protein sensitized DC(HST1-DC)and the combined sensitized DC(GH-DC), the mouse bone marrow-derived DCs were sensitized with fusion protein to obtain the fusion protein sensitized DC vaccines. B16F10 melanoma cells were transplanted into C57BL/6J male mice to construct a melanoma model(1×106 cells per mouse), and DC vaccine was injected for treatment. The antitumor efficacy of DC vaccine was explored by in vitro and in vivo experiments. Flow cytometry analysis showed that the fusion protein can effectively stimulate DC into differentiation and maturation; in the animal experiment, the inhibition rate of melanoma treated with G3G6-DC was 35. 75%, that of HST1-DC group and combination group were 34. 03% and 55. 74%. It was initially proved that both G3G6-DC and HST1-DC can effectively inhibit the growth of transplanted tumors of melanoma B16F10 cells in mice, and the combination therapy is superior to the single therapy.

Objective This article conducted the statistical analysis of SCI papers published during 2013-2017 at the first affiliated hospital of Sun Yat-sen university ,to understand the SCI paper outcomes as to provide reference for future policy making and research administration development .Methods We analyzed the SCI papers published by the First Affiliated Hos-pital of Sun Yat-sen University from 2013 to 2017 ."Article" and"Review" type SCI papers published by the hospital as the first completion unit were statistically analyzed from the aspects of quantity ,impact factors ,journals and discipline distribu-tion .Results A total of 2268 SCI papers were published in 5 years ,distributed in 1162 journals .The quantity and the average impact factor both increased year by year ,but mainly concentrated in traditional dominant disciplines .Conclusions The SCI papers were increasing annually since 2013 .However ,we still need to improve the quantity and quality of high-level articles ,to promote the development of disciplines ,to strengthen the construction of public experimental platforms ,to continue building talent teams ,to improve the reward and evaluation system ,and to further enhance the overall scientific research level of the hospital .

Objective To retrospectively analyze the clinical distribution and changes in antimicrobial resistance profiles of Staphylococcus aureus (S. aureus). Methods We collected clinical specimens of S. aureus from The First Hospital of China Medical University. The Vitek-2 and BD Phoenix 100 were performed for bacterial identification and drug sensitivity tests,and WHONET 5.6 was used to analyze the data. Results From 2007 to 2016,there were 3 377 unrepeatable strains of S. aureus,including 1 705 that were methicillin resistant S. aureus (MRSA). The isolation rate of S. aureus was 9.4 ％ and of these,50.5 ％ were MRSA. There were 776 S. aureus specimens from outpatients or the emergency department,including 16.8 ％ MRSA,and 2 011 S. aureus from inpatient departments,including 60.2 ％ MRSA. The main sources of specimens were sputum (41.8 ％),pus (17.9 ％),and body secretions (17.5 ％). The average resistance rates of MRSA for erythromycin,ofloxacin,ciprofloxacin,gentamycin,and tetracycline were higher than 75.0 ％. The average resistance rate of methicillin sensitive S. aureus (MSSA) for erythromycin was up to 76.8 ％,and for tetracycline,gentamycin,ciprofloxacin,and ofloxacin,were less than 25.0 ％. In 10 years,the average resistance rates of MRSA and MSSA for 11 kinds of common antibiotics had no obvious change. Conclusion The constituent rate of MRSA was high in The First Hospital of China Medical University,especially from the areas that were not sterile,suggesting that clinicians should pay attention to the identification of infection and sources for MRSA,which were from such areas. Hospital infection control should be focused on at the same time,in order to reduce the incidence of MRSA.