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Objective A magnetic resonance nano-contrast agent containing trimanganese tetroxide was synthesized, its characterization was explored, and its contrast efficiency and safety performance were explored. Methods Polyacrylic acid(PAA) was used as a pH-responsive polymer to react with manganese sulfate to obtain nanoparticles. The molecular formula of the synthesized nanoparticles was determined by X-ray photoelectron spectroscopy and X-ray diffractometer. Transmission electron microscopy, particle size analyzer, inductance Coupled plasma emission spectroscopy and 7.0 T magnetic resonance imaging instruments were used to study the morphology, magnetic resonance properties, cell biocompatibility, and material stability of nanoparticles. Results Manganese oxide samples were obtained by the reaction of glutathione, polyacrylic acid and MnSO4. The sample was observed under transmission electron microscopy as petal-shaped nanoparticles with a diameter of about 100 nm. X-ray photoelectron spectroscopy and X-rays diffractometer results showed that its composition was Mn3O4; at pH 4.5, the 24 h Mn2+release was still less than 0.5%, which proved its good stability and safety; magnetic resonance imaging results showed that the pH was acidic under the conditions, the manganese oxide nanoparticles had extremely high contrast performance. When the pH was 4.5, the longitudinal relaxation rate reached 13.0 mmol-1·s-1, indicating that it could respond to the tumor microenvironment; CCK-8 showed that co-cultivation of the manganese oxide nanoparticles with gingival fibroblasts(HGF) for 24 h and 48 h did not produce cytotoxicity, proving that the material had good biocompatibility. Conclusion A new nano-contrast agent with trimanganese tetroxide was successfully synthesized, which has good biocompatibility and the highest contrast efficiency under acidic conditions, providing a basis for its further clinical research.

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Objective To construct eukaryotic expression plasmid encoding MAGE-A3, preparein vitrotranscribed mRNA and express MAGE-A3 protein in NIH/3 T3 cells. Methods The whole gene of MAGE-A3 was amplified by RT-PCR and cloned into pcDNA3.1(+) expression vector to build pcDNA3.1-MAGE. Subsequently, the template DNA for transcriptionin vitrowas prepared by PCR.Then, the template DNA was transcribed into MAGE-A3 RNAs using MEGAscript T7 transcription kit. The transcripts were added a poly(A) tail to the 3' termini and purified by using transcription clean-up kit. After transfection of the purified MAGE-A3 mRNA into NIH/3 T3 cells, Western blot analysis was used to confirm the expression of MAGE-A3 protein. Results The gene inserted into the recombinant vector was proven to be completely identical with the sequence of the MAGE-A3 gene in online database. The ratio of A260/A280of the purified mRNA was 1.92, and the concentration was 872.3 ng/μl. The length of MAGE-A3 mRNA was about 500 bp. After MAGE-A3 mRNA transfected into NIH/3 T3 cells, MAGE-A3 protein could be produced in cells and the size of protein was 35 ku. Conclusion Eukaryotic expression plasmid encoding MAGE-A3 is successfully constructed and the high-purity MAGE-A3 mRNA is obtainedin vitro. The mRNA can be translated into MAGE-A3 protein in NIH/3 T3 cells.

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Objective To investigate the effects of Bruton's tyrosine kinases(Btk) inhibitor, ibrutinib, on inflammatory response in high glucose-induced macrophages and to discover the underlying mechanisms. Methods In this study, bone marrow-derived macrophages(BMMs) were used. After the optimization of the experimental conditions, the BMMs were divided into four groups: low-glucose group(LG), low-glucose+ibrutinib control group(LG+PCI-32765), high-glucose group(HG), and high-glucose+ibrutinib group(HG+PCI-32765). The macrophages were detected by flow cytometry. The expression of inflammatory cytokines in cell and in cell supernatant, including the monocyte chemo-attractant protein-1(MCP-1), the tumor necrosis factor-alpha(TNF-α) and the interleukin-1 beta(IL-1β) and the mRNA, were detected by enzyme-linked immuno sorbent assay and quantitative real-time PCR. The iNOS, Btk, ERK, JNK, p38 MAPK, NF-κB p65, IκB and the corresponding phosphorylated proteins were detected by Western blot. The activation of macrophages and nuclear transfer of p65 were detected by laser confocal microscopy. Results Compared with the LG group, the expression of inflammatory cytokines in the HG group increased(P<0.05), while that decreased in the HG+PCI-32765 group compared with the HG group(P<0.05). The expression of p-Btk was higher in the HG group(P<0.01), and the p-ERK, p-JNK, p-p38 MAPK, NF-κB p-p65 and p-IκB in the HG group were also higher(P<0.05) compared with the LG group, and the Btk inhibitor, PCI-32765, could reduce the expression of p-Btk, p-ERK, NF-κB p-p65 and p-IκB(P<0.05). The macrophages were activated by high-glucose, and the expression of iNOS increased(P<0.01), while PCI-32765 could reduce its expression(P<0.05). By using laser confocal microscopy, it was found that under high-glucose stimulation, p65 had nuclear-transfer, and PCI-32765 could reduced it. Conclusion Ibrutinib is able to inhibit the high glucose-induced activation of macrophages and suppress the release of inflammatory cytokines by down-regulating the ERK and the NF-κB signaling pathways.

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Objective To investigate the effects and molecular mechanisms of histone deacetylase(HDAC) inhibitors on the regulation of FKBP3 in esophageal cancer cells ECA109 and KYSE30. Methods Esophageal cancer cells ECA109 and KYSE30 were treated with HDAC inhibitors for 48 h and then harvested and checked for the protein and mRNA levels of FKBP3 by Western blot and qPCR, respectively. HDACs siRNA knockdown experiments were conducted in ECA109 cells and then the expression of FKBP3 were checked. The STRIING database was used to obtain the interaction network between FKBP3 and HDACs. Results The broad-spectrum HDAC inhibitor Vorinostat, and specific HDAC inhibitor Entinostat which targets HDAC1 and HDAC3, both showed inhibitory effects on FKBP3 not only on protein level but also on mRNA level. The specific knockdown of HDAC1 or HDAC2 also led to decreased expression of FKBP3, whereas knockdown of HDAC3 had no such effect. The database indicated that FKBP3 interacted with HDAC1 and HDAC2 and might form a complex to perform biological functions. Conclusion In esophageal cancer cells, HDAC inhibitors can inhibit the expression of FKBP3, which is likely to be achieved by inhibiting HDAC1 and HDAC2.

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Objective To investigate protective effect and mechanism of vitexin on rat primary cardiomyocytes induced by hypoxia/reoxygenntion injury via regulating autophagy and autophagic flow. Methods Hypoxia/reoxygenation(H/R) of primary cardiomyocytes was used to simulate ischemia-reperfusion injury. The viability of cardiomyocytes was tested by CCK8. LDH levels in cardiomyocyte supernatant were detected by kit. ROS levels were detected by DCFH-DA fluorescent probe. Primary cardiomyocytes were infected with mRFP-GFP-LC3, and the number of Autophagolysosomes and autophagosomes was evaluated. Beclin1, LC3Ⅱ/Ⅰ and P62 protein expression were detected by Western blot. Results After hypoxia and reoxygenation(H/R) of primary cardiomyocytes, the LDH value of primary cardiomyocytes in the H/R group was significantly higher than that in the control group, and the ROS level significantly increased, the doses of vitexin could significantly inhibit the release of LDH from H/R cardiomyocytes and reduce the ROS level in cardiomyocytes. The primary cardiomyocytes were transfected with mRFP-GFP-LC3 virus, and the results showed that compared with the control group, the cardiomyocytes in the H/R group showed significant enhancement of autophagy and autophagy flow. suggesting that autophagosomes accumulated in myocardial cells after H/R, and autophagolysosomes increased accordingly; The vitexin dose groups could inhibit autophagy and increase autophagy flow in cardiomyocytes after H/R, and reduce the accumulation of autophagosomes in cardiomyocytes. In addition, Western blot results showed that compared with the normal control group, the expression of autophagy proteins Beclin 1, and LC3Ⅱ in primary myocardial cells of the H/R group increased, and the ratio of LC3Ⅱ/Ⅰincreased, P62 protein in cardiomyocytes was down regulated; Compared with the H/R group, vitexin inhibited Beclin 1 up-regulation and decreased the expression of LC3Ⅱ protein, the ratio of LC3Ⅱ/Ⅰreduced, and the expression of P62 protein also increased in cardiomyocytes. Conclusion Vitexin has a significant protective effect on H/R injury in rat primary myocardial cells, and its mechanism may be related to the inhibition of ROS production, autophagy and autophagic flow enhancement, and the accumulation of autophagosomes after H/R in myocardial cells.

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Objective To observe the dynamic changes of Bruton's tyrosine kinase(Btk), phosphorylated Btk(p-Btk), nuclear factor κB(NF-κB), nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3), interleukin-1β(IL-1β), tumor necrosis factor-α(TNF-α) in acute liver injury induced by acetaminophen(APAP) in mice, and preliminarily explore the role of Btk in acute liver injury induced by APAP. Methods 54 mice were randomly divided into 9 groups, including control group, APAP 0.5 h group, APAP1 h group, APAP3 h group, APAP6 h group, APAP12 h group, APAP24 h group, APAP36 h group and APAP48 h group. After fasting for 12 h, mice in the corresponding groups were sacrificed after a single intraperitoneal injection of APAP(300 mg/kg) for 0.5 h, 1 h, 3 h, 6 h, 12 h, 24 h, 36 h and 48 h. Serum alanine aminotransferase(ALT) and aspartate aminotransferase(AST) were measured by chemical method. Liver tissue damage was observed by HE staining. IL-1β and TNF-α in liver tissue homogenate were measured by ELSIA.The expression of Btk, p-Btk,NF-κB and NLRP3 was determined by Western blot. Results Compared with the control group, serum ALT(F=100.968,P=0.000), AST(F=73.539,P=0.000), liver necrosis degree(F=29.845,P=0.000), liver Btk(F=441.280,P=0.000), p-Btk(F=1 323.022,P=0.000), NF-κB(F=133.125,P=0.000), NLRP3 levels(F=820.095,P=0.000) and the content of IL-1β(F=8.643,P=0.000), TNF-α(F=20.545,P=0.000) all changed. Among them, the various kinds index of 24 h was respectively the highest. Conclusion Liver injury induced by single intraperitoneal injection of APAP shows dynamic changes, which pathogenesis may be related to APAP-induced activation of Btk, resulting in formation of NLRP3, activation of NF-κB and increase of inflammatory factors.

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Objective To investigate the effect of BET family small molecule inhibitor JQ1 combined with sorafenib on the proliferation and apoptosis of liver cancer cells and its mechanism. Methods The proliferation inhibition rate of sorafenib, JQ1 and JQ1 combined with sorafenib on HepG2 and Bel-7402 human liver cancer cells was detected by MTT assay, the change of apoptosis rate was detected by flow cytometry, the expression of c-MYC, Bcl-2 and BIM proteins was detected by Western blot. Results Compared with sorafenib and JQ1 alone, the proliferation inhibition rate and apoptosis rate of liver cancer cells increased when treated with JQ1 combined with sorafenib, the expression of c-MYC and Bcl-2 protein was down-regulated and the expression of BIM protein was up-regulated after treated with JQ1 combined with sorafenib on liver cancer cells. Conclusion A certain concentration of JQ1 can enhance the proliferation inhibition and apoptosis effects of sorafenib on liver cancer cells, and its mechanism may be related to the down-regulated expression of c-MYC and Bcl-2, and the up-regulated expression of BIM.

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Objective To examine the effect of SNAP29 on Cisplatin resistance of gastric cancer cells, compare the expression of SNAP29 in gastric cancer and normal gastric tissues and analyze the clinicopathological significance of SNAP29 in gastric cancer patients. Methods Western blot was used to detect the SNAP29 protein levels in cell lines. MTT assay and soft agar colony formation assay were performed to detect cell viability and cell colony formation respectively, and for further examine the overexpression of SNAP29 to promote Cisplatin resistance in gastric cancer cells. Immunohistochemistry was carried out to detect the expression of SNAP29 protein in gastric cancer and normal gastric tissues, and to analyze the correlation between SNAP29 levels and pathological parameters in gastric cancer patients. Results MTT and soft agar colony formation assays showed that the overexpression of SNAP29 promoted Cisplatin resistance in gastric cancer cells MKN-45 and AGS; there was no significant difference of SNAP29 protein levels in gastric cancer and normal gastric tissue; the expression levels of SNAP29 were correlated with lymph node metastasis and tumor stage in gastric cancer patients, but not with patients' age, gender, tumor size or tumor grade. Conclusion Overexpression of SNAP29 promotes Cisplatin resistance in human gastric cancer cells. The expression levels of SNAP29 are positively correlated with lymph node metastasis and tumor stage in gastric cancer patients. Therefore, SNAP29 is an important biomarker for diagnosis and treatment in gastric cancer.

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Objective To investigate the effect and mechanism of ABT-737-mediated apoptosis in Caenorhabditis elegans( C. elegans) of living animals. Methods Fluorescent dye method was used to detect the apoptosis of germ cell in wild-type C. elegans under different concentrations of treatment. Meanwhile,reactive oxygen species( ROS) fluorescent strain together with different gene mutant strains of C. elegans were used to elucidate the mechanism of ABT-737-induced apoptosis. Results After treated with ABT-737 at concentrations of 0,10,and 20μmol/L,the number of apoptotic cells in wild-type C. elegans increased from 2. 31 ± 0. 06 to 4. 02 ± 0. 09 and4. 40 ± 0. 08. However,there was no change of apoptosis in C. elegans lacking the expression of the mitogen-activated protein kinase pathway( MAPK/JNK pathway,mek-1/jnk-1) and DNA damage response pathway( egl-1,hus-1,cep-1) genes. In addition,ABT-737 increased the fluorescence intensity in the SOD3 fluorescent strain,indicating the ROS level was increased in C. elegans. Conclusion ABT-737 induces apoptosis of C. elegans germ cells in a dose-dependent manner at the level of live animals. Oxidative stress,DNA damage response pathway and MAPK/JNK signaling pathway are involved in ABT737-induced apoptotic signaling.

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Objective To investigate the expression and effects of PHD finger-like domain-containing protein 5 A(PHF5 A) in gastric cancer cells and to explore its mechanism. Methods QPT-PCR and Western blot were used to detect the expression levels of PHF5 A mRNA and protein in normal gastric cancer cell line GES-1 and gastric cancer cell lines MKN45,MGC803 and AGS. MGC803 cells transfected with negative control empty lentivirus were used as the control group. Two knockdown groups which were transfected with two different interfering sequences lentivirus against the PHF5 A gene were used as the experimental groups. The proliferation ability was observed by cell proliferation curves and colony formation assay. The migration ability was observed by wound healing assay. Western blot was used to detect the expression levels of some signaling molecules such as Transcription factor p65(NF-κB p65), NF-kappa-B inhibitor alpha(Iκbα), p-Iκbα and Cyclin-D1-binding protein(Cyclin D1) in NF-κB signal transduction pathway. Result The expression levels of PHF5 A mRNA and protein in gastric cancer cells were significantly higher than those in normal gastric mucosal epithelial cells. After knockdown the expression of PHF5 A gene, the level of PHF5 A protein decreased. Compared with the control group, the proliferation, migration and colony formation ability of MGC803 cells in two PHF5 A knockdown groups sh1 and sh2 decreased obviously. At the same time, the result of western blot showed that the expression of NF-κB,p-IκBα,Cyclin D1 significantly decreased in experiment groups(P<0.05). Conclusion PHF5 A is highly expressed in gastric cancer cells. Lentivirus-mediated inhibition of PHF5 A gene expression can reduce the proliferation and migration ability of MGC803 cells. The mechanism may be related to the inhibition of NF-κB signaling pathway.

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Objective To observe whether biochanin A(Bioch A) exerts protective effects on MPP+-induced PC12 cells apoptosis. Methods Effects of MPP+and Bioch A on PC12 cells viability were detected by MTT assay to screen out the MPP+-induced apoptosis dose and appropriate Bioch A dose. Conventional cultured PC12 cells were divided into: Control group, MPP+(1 μmol/L) group, Bioch A(1.25 μmol/L) group, Bioch A(2.5 μmol/L) group, Bioch A(5 μmol/L) group and Estradiol(E2)(0.1 μmol/L) group. Reactive oxygen species(ROS) was detected by DCFH-DA probe method. Apoptosis rate was detected by Annexin V-FITC/PI double staining. The expression levels of cleaved Caspase-3 and cleaved Caspase-9 were detected by Western blot method. Results Compared with the control group, ROS content increased in MPP+group. Compared with the MPP+group, ROS content decreased in Bioch A(2.5, 5 μmol/L) groups. Compared with the control group, the apoptosis rate and the levels of cleaved Caspase-3 and cleaved Caspase-9 increased in MPP+group. Compared with the MPP+group, the rate of apoptosis and the expression levels of cleaved Caspase-3 and cleaved Caspase-9 decreased in Bioch A(2.5, 5 μmol/L) groups. Conclusion Bioch A exerts protective effects on MPP+-induced PC12 cells apoptosis.

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Objective Cancer-associated pancreatic stellate cells(CaPSCs) and normal pancreas-associated pancreatic stellate cells(NaPSCs) were selected as entry points to screen circRNA related proliferation and migration of pancreatic cancer cell line Panc-1. And to explore strategies for targeted therapy of pancreatic cancer. Methods CaPSCs1～5and NaPSCs1～5were isolated and cultured from pancreatic cancer tissues of 5 pancreatic cancer patients and normal pancreas tissues of 5 patients with benign pancreatic disease. After they were co-cultured with Panc-1, and then the proliferation ability of Panc-1 was tested by CCK-8 experiment. CaPSCs1, which had the strongest promoting effect on Panc-1 proliferation, and NaPSCs1, which had the weakest effect, were screened.And then RNA high-throughput sequencing was used to analyze the differential expression profiles of circRNA between the two kinds of cells,and qRT-PCR was used to verify the first three circRNAs with the most differential expression. At the same time,KEGG was used to enrich the biological functions and signaling pathways of differential circRNA,and microRNA target prediction software was used to predict differential circRNA downstream genes( microRNA). Results Compared with Na PSCs1,CaPSCs1group had 841 differential circRNAs( 453 down-regulated and 388 up-regulated),8 155 differential mRNAs( 4 226 down-regulated and 3 929 up-regulated),and 73 differential microRNA( 16 down-regulated and 57 up-regulated). Among them,the most significantly expressed circRNAs were chr7: 154954255 | 154998784,chr10: 12081472 | 12120267,and chr10: 76909966 | 77019099. The differences were statistically significant( P<0. 05). The corresponding target genes( microRNA) were hsa-miR-612,hsa-miR-1301-3 p and hsa-miR-4459. The major signaling pathways enriched by differential circRNA were the Toll-like receptor signaling pathway,the TNF signaling pathway,the T cell receptor signaling pathway,and the HIF-1 signaling pathway. The biological processes were mainly focused on cell-substrate junction and cell-substrate adherens junction etc. Conclusion CircRNAs are up-regulated in Ca PSCs: chr7: 154954255 | 154998784,chr10: 12081472 | 12120267,chr10: 76909966 | 77019099 and their downstream target genes( microRNAs) are likely to interact with PSCs to promote pancreatic cancer cell proliferation and migration through multiple signaling pathways.

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Objective To explore whether dendrobium polysaccharide(DOP) can inhibit the apoptosis of nerve cells caused by tumor necrosis factor-α(TNF-α) and the optimal concentration of DOP. Methods Mouse hippocampal neurons(HT22) were cultured with different concentrations of TNF-α to determine the optimal concentration of TNF-α induced HT22 cell apoptosis. After co-cultured with different concentrations of DOP and the optimal concentration of TNF-α for 24 hours, the expression of apoptosis related genes and proteins was detected by PCR and Western blot to find out the inhibition of DOP on HT22 cells. At the same time, the number and proportion of HT22 cells apoptosis were observed by Giemsa staining, Hoechst staining, Tunel staining and flow cytometry. Results Compared with the normal culture group, TNF-α increased the expression of apoptosis related genes in HT22 cells, and the optimal concentration was 5 ng/ml(P<0.000 1). Compared with the 5 ng/ml TNF-α group, the expression of apoptosis gene in HT22 cells was inhibited by different concentrations of DOP, especially in the 20 μg/ml and 25 μg/ml groups(P<0.001), and the expression of related proteins in the 20 μg/ml and 25 μg/ml groups, the number and proportion of apoptosis in HT22 cells were significantly lower than those in the 5 ng/ml TNF-α group(P<0.001). Conclusion DOP can inhibit the apoptosis of HT22 cells induced by TNF-α, and the best inhibition effect is at the concentration of 20 μg/ml and 25 μg/ml.

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Objective To investigate the effect of humidex on traffic injury. Methods A Poisson generalized linear regression combined with distributed lag non-linear model was applied to analyze the relationship between humidex and the incidence of traffic injury. Stratified analysis was carried out according to gender and age. Results The relationship between traffic injury and humidex is nonlinear. The risk effect increased first and then decreased with the increase of humidity, but the overall risk effect was statistically significant. The adverse effect of humidex(25 percentile of humidex) was the largest on the day of exposure(P25:RR=1.102(1.010～1.201)), and ended in 5-days lag. Subgroup analysis indicated that male and the population who aged>14-<65 were affected by humidex at lag 0-5 days. Conclusion Humidex can significantly increase the risk of traffic injury, and has the lagged effects.

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Objective To compare the effect of rigid/flexible artificial insemination catheter on pregnancy outcome of artificial insemination by donor. Methods The clinical data of 2 747 artificial insemination by donor(AID) cycles were analyzed retrospectively. According to the rigid/flexible artificial insemination catheter used in the operation, they were divided into rigid catheter group and flexible catheter group. According to the follicular development scheme, they were furtherly divided into rigid catheter-natural cycle group, rigid catheter-promoted ovulation cycle group, flexible catheter-natural cycle group and flexible catheter-promoted ovulation cycle group. And according to the times of intrauterine insemination(IUI) in each AID cycle, they were furtherly divided into rigid catheter-single insemination group, rigid catheter-double insemination group, flexible catheter-single insemination group and flexible catheter-double insemination group. Then the biochemical pregnancy rate, clinical pregnancy rate, live birth rate, multiple pregnancy rate and abortion rate among the groups were compared and analyzed. Results The biochemical pregnancy rate, clinical pregnancy rate and live birth rate of the flexible catheter-single insemination group were higher than those of the rigid catheter-single insemination group, and the difference had statistical significance(P<0.05). The difference between the abortion rates of the two groups had no statistical significance. In addition, the biochemical pregnancy rate, clinical pregnancy rate, live birth rate, multiple pregnancy rate and abortion rate of other rigid catheter groups and flexible catheter groups had no statistical significance(allP>0.05). Conclusion There is no difference in pregnancy outcome between using flexible catheters and rigid catheters in AID treatment. However, when there is only single IUI in an AID cycle, the pregnancy outcome of using flexible catheters is better than that of using rigid catheters.

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Objective To compare and explore dosimetric parameters of three differentradiation treatment plans and cardio-pulmonary protection for middle thoracic esophageal carcinoma. Methods A total of twenty-four patients with middle thoracicesophageal cancer were included and three radiation treatment plansfor fixed filed intensity modulated radiotherapy(IMRT), volumetric modulated arc therapy(VMAT)and tomotherapy(TOMO) were designed for each patient.Conformity index(CI), homogeneity index(HI), dosimetric parameters of organs at risk, the mean treatment time and the number of monitor units(MU) of the three plans were compared. Results Compared with VMAT and IMRT, TOMO showed better HI(P=0.01), and there was no significant difference in CI(P=0.34)among three differentradiation treatment plans,TOMO was significantly better than those of VMAT and IMRT in lung V30and V20(P<0.05); There was no statistically significant difference between TOMO and VAMT in lung V10、V5and Dmean(P>0.05), VMAT was significantly better than IMRT in lung V20、V5(P<0.05); There was no significant difference in heart V30,V40,Dmean(P>0.05) and the highest dose of spinal cord(Dmax)(P>0.05) among three plans;TOMO had the longest treatment time and the most number of MU, VMAT was the fastest to execute, with an average time reduction of 66% compared to TOMO. Conclusion In radiotherapy for middle thoracic esophageal cancer, TOMO is more advantageous than VMAT and IMRT in terms of HI and lung protection, and there is no significant difference in CI and dosimetric parameters of heart and spinal cord.TOMO requires longer treatment time and more number of MU;VMAT has the shortest treatment time and better plan quality than IMRT, so it is the most cost-effective treatment.

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Objective To analyze the pregnancy outcome of twins in infertile women with polycystic ovary syndrome(PCOS) after the frozen-embryo transfer. Methods Retrospective analysis was made on 1449 patients who received in vitro fertilization-frozen embryo transfer and obtained twin pregnancy. The PCOS group was 421 patients with infertility caused by polycystic ovary syndrome, and the control group was 1028 patients with infertility caused by fallopian tube factors alone in the same period.The two groups of patients were further respectively divided into non-overweight group(BMI<24 kg/m2) and overweight group(BMI≥24 kg/m2),which were recorded as: non-overweight PCOS group, overweight PCOS group; non-overweight control group, overweight control group. General information, pregnancy complications, and neonatal outcomes of non-overweight PCOS group and non-overweight control group were compared, which were also compared between the overweight PCOS group and the overweight control group. Results The abortion rate and late abortion rate in non-overweight PCOS group were higher than those in the non-overweight control group(P<0.05). There was no significant difference in early abortion rate, premature delivery rate, morbidity of hypertensive disorders of pregnancy(HDP)、gestational diabetes mellitus(GDM), cesarean section rate, average weight and malformation rate of newborn between the two groups. The mean neonatal birth weight in overweight PCOS group was lower than that in overweight control group;abortion rate and late abortion rate in PCOS group were higher than those in overweight control group(P<0.05).There was no significant difference in early abortion rate, premature delivery rate, morbidity of HDP、GDM, cesarean section rate and neonatal malformation rate between the two groups. Conclusion PCOS after frozen-embryo transfer increase the pregnancy abortion rate and late abortion rate of twins, and PCOS in overweight patients reduce the neonatal birth weight.

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Objective To investigate the effect of different degree of antiplatelet aggregation therapy and thromboelastic diagram(TEG) on cerebral microbleeds in patients with atherosclerotic cerebral infarction. Methods A total of 150 patients diagnosed with acute cerebral infarction and given aspirin were examined by magnetic sensitive cranial magnetic resonance(SWI) and TEG and followed up for 90 days. According to whether the number of CMBS increased by>3 and the result of TEG detection compared with on admission,the patients were divided into CMBs and no CMBs group, platelet aggregation in good group(aspirin inhibition rate>75%), the effect of general group(50% Results ① CMBs and arachidonic acid(AA) inhibition rate, uninhibited platelet activity(MA-AA), Angle, coagulation reaction time(RT), age, diabetes, high-density lipoprotein(HDL-C), NIHSS score, leubic osteoporosis had statistically significant differences(P<0.05). ②The related variables selected from the single factor analysis were selected into the logistic multi-factor regression analysis, and age, HDL-C, AA inhibition rate, MA-AA, RT were risk factors for CMBs(P<0.05). ③The difference between the good group and the invalid group was statistically significant in CMBs, number of stroke, KT, RT and MA-AA(P<0.05). There was no significant difference in CMBs between the general group and the invalid group(P>0.05), and there was significant difference in the number of stroke, time of blood clot formation(KT), RT, and MA-AA values(P<0.05). There was no significant difference in the number of stroke between the good group and the general group(P>0.05), but there was significant difference in CMBs, RT value and MA-AA(P<0.05). Conclusion KT, RT and MA-AA are effective indicators of coagulation function and antiplatelet ability. Advanced age, HDL-C, high AA inhibition rate, low MA-AA and prolonged RT are risk factors for CMBs. Antiplatelet therapy under the guidance of TEG keeps the inhibition rate of aspirin between 50% and 75%, which is more scientific in the secondary prevention of cerebral infarction. It is of guiding significance to reduce hemorrhage transformation and CMBs after cerebral infarction and prevent long-term cognitive decline in patients.

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Objective To explore the decision-making function under clear risk condition in patients with chronic obstructive pulmonary Disease( COPD). Methods Game of dice task( GDT) with clear risk probability was used to test the risk decision-making ability of 34 patients with COPD( COPD group) and 30 healthy control( HC group) matched with their demographic data. At the same time,the background cognitive functions such as verbal fluency test,digit span test were detected. Results Within the Game of Dice Test,the COPD group( 12. 67 ±3. 11) was more likely to choose the risk option( F =-3. 594,P = 0. 001) than the HC group( 8. 09 ± 6. 65).Compared with the COPD group( 23. 30 ± 30. 73),the HC group( 58. 46 ± 34. 14) was more likely to choose the safety option temporarily after losing money,and the difference of negative feedback utilization rate between the two groups was statistically significant( F =-4. 122, P<0. 001). The final total assets of the COPD group(-1 623. 53 ± 4 121. 57) were usually negative,while those of the HC group( 966. 67 ± 2 785. 60) were all profitable,with a statistically significant difference( F =-2. 975,P = 0. 004). Conclusion Cognitive decline was observed in patients with COPD,and significant changes were observed in decision-making ability under clear risk probability,which was associated with negative feedback utilization.

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Objectives A randomized, double-blind, controlled study was investigated the effectiveness and safety of skin care products for the purpose of repairing the skin barrier on the treatment of patients with sensitive skin. Methods According to the inclusion and exclusion criteria, 80 patients with sensitive skin were randomly selected as the sensitive group while 50 healthy people were used as the control group, and they were all treated with skin barrier repair agent and followed up at baseline and after 14 days and 28 days. The doctors made a assessment based on the differences in the patient's skin lesions, non-invasive test results and so on. Moreover, all subjects made self-assessment based on their own feelings. Statistical methods were applied to analyze the data. Results After 4 weeks of using the product continuously, patients with sensitive skin showed significant improvement in transepidermal water loss, Stratum Corneum Hydration and Skin Elasticity. The improvement rates were 92.0%, 76.0% and 65.3%, respectively. The control group had reduced epidermal oil content and enhanced skin elasticity(P<0.05). There was no improvement in the red area of visia in the two groups of subjects. The doctors evaluated the clinical symptoms of dry and flushing and the quality of life in sensitive skin patients significantly improved. And most subjects felt comfort and satisfaction. 89.3% of the subjects had high self-assessment satisfaction, and no severe skin adverse reactions were observed. Conclusion Repairing the skin barrier function has a significant clinical effect on the treatment of sensitive skin diseases, and it has a multiplier effect on the clinical treatment of sensitive skin processes.

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Objective To investigate the correlation between the cognitive impairment in alzheimer's disease(AD) and subdivisions of anterior cingulate cortex(ACC). Methods Forty-five patients with alzheimer's disease and forty matched heathy controls(HC) were recruited. Cognitive abilities were accessed with neuropsychological assessments. The grey matter volume(GMV) of ACC subdivisions between two groups was calculated and compared. Linear regression model was conducted for observing the relationship between the GMV of subdivisions and the cognitive impairment. Results All subdivisions of ACC of AD patients were atrophy compared to HC. The GMV of the right pregenual and subgenual ACC were crucial for the cognitive impairment, which implied the more atrophied for the subgenual ACC, the more severe for the cognitive impairment. Conclusion The pregenual and subgenual ACC played a role in the cognitive impairment in the AD progress, which might be potential targets for future therapy.

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Objective To investigate the improvement of 12-lead ecg indexes such as T-wave amplitude, Tpeak-Tend(Tp-Te) in patients with chronic coronary total occlusion(CTO) of single-branch before and after percutaneous coronary intervention(PCI), and to compare the improvement of cardiac function(NYHA) grading in six months of follow-up. Methods 192 consecutive patients with single vessel CTO who underwent PCI were divided into two groups according to with or without old myocardial: CTO group with old myocardial infarction(MI CTO group,106 cases) and CTO group without old myocardial infarction( non MI CTO group,86 cases). The repolarization indexes before and after revascularization and NYHA grading after six months were compared. Results Among the ecg indexes of the two groups,the preoperative T-wave amplitude of the inferior wall leads,and the TpTe indexes of the inferior wall leads and the anterior wall leads were significantly different( P<0. 05). There was statistically significant difference in Tp-Te of lead Ⅰ and Ⅲ after revascularization( P<0. 05). In the MI CTO group,both the T-wave amplitude and Tp-Te,indexs of postoperative repolarization,showed statistically significant difference compared with the preoperation( P<0. 05). After revascultation in the non-MI CTO group,there were statistically significant differences in Tp-Te of the seven leads( Ⅰlead,Ⅲ lead,AVR lead,AVF lead,V4 lead,V5 lead and V6 lead)( P<0. 05). Follow-up for 6 months showed no statistically significant difference in NYHA grading between the groups,but there was statistically significant difference in NYHA grading within the groups( P<0. 05). Conclusion Both repolarization index and cardiac function are improved after revascularization. CTO patients without old myocardial infarction are caused by Tp-Te improvement,while CTO patients with old myocardial infarction are caused by improvement of T wave amplitude and Tp-Te.

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Objective To study the serum interleukin-6 concentration and phenotypes and phagocytosis of neutrophils for the diagnosis and staging of sepsis. Methods A total of 121 patients were collected between January 2018 and June 2019. The patients were divided into two groups: the group of systemic inflammatory response syndrome(SIRS, 95 cases,including 19 cases of non-sepsis, 56 cases of sepsis and 20 cases of septic shock), the group of local infection(26 cases). Meanwhile, 20 cases of healthy volunteers were selected as the control group. Cytokines(IL-2, IL-4, IL-6, IL-10, IFN-γ, TNF-α), PCT, hsCRP, and WBC counts were measured, and the phenotypes(CD64, CD11 b and CD62 L) of peripheral blood neutrophils(PBNs) and their phagocytic function were determined. Results The levels of serum IL-6 and IL-10 were found to be highest in the patients of SIRS group(P<0.01), followed by those of the local infection group and the control(P<0.01). The patients of septic shock had the highest level of serum IL-6(P<0.01), followed by those of septic group and non-septic group(P<0.01), but no significant difference of IL-10 levels was noted between the groups of septic shock and sepsis(P>0.05). Compared with those of low IL-6 concentration in the groups, patients with high serum IL-6 level simultaneously presented elevated levels of hs-CRP, PCT and IL-10(P<0.01), accompanied by increased expressions of CD11 b and CD64(P<0.01). Additionally, the PBNs phagocytosis was found to be enhanced in the patients of high IL-6 level when compared with those of low IL-6 level(P<0.01). Conclusion The serum level of IL-6 in the patients with sepsis gradually increased as the disease progresses, and the highest level of serum IL-6 may be noted in the patients with sepsis shock, followed by those of sepsis and non-sepsis consecutively. An elevated level of serum IL-6 was frequently accompanied by enhanced neutrophil phagocytosis and high expressions of CD64 and CD11 b in the patients with sepsis. Taken together, examination of serum IL-6, which is closely associated with clinical stages of sepsis, is quite valuable for diagnosis of the disease. Thus tracking and monitoring of serum IL-6 may provide a reference for the clinical diagnosis and progress of sepsis, worth being promoted practically.

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Objective To explore the relationship between expectant treatment and perinatal outcome of early onset severe preeclampsia. Methods 244 cases of early onset severe preeclampsia with singleton were selected as the study object. After admission, the patients were divided into two groups: immediate termination group(89 cases) and expectant treatment group(155 cases). The expectant treatment group was divided into four groups according to gestational weeks: group QA(<28 weeks, 15 cases), group QB(28-30 weeks, 36 cases), group QC(30+1-32 weeks, 47 cases), group QD(32+1-34 weeks, 57 cases). Results ① Compared with immediate termination group, the birth weight increased, HELLP syndrome、placental abruption、ICU occupancy rate and neonatal mortality rate decreased in expectant treatment group(P<0.05). ② The rate of cesarean section in group QC and group QD was higher than that in group QA(P=0.002). ③ The birth weight increased with the prolong of gesta-tion in group QA, QB, QC and QD; the 5-minute severe asphyxia rate of group QB、QC and QD was lower than that of group QA,and group QD was lower than group QB; the stillbirth of group QB、QC and QD was lower than that of group QA,group QD was lower than group QB; the neonatal mortality rate of group QD was lower than that of group QA and QB; the survival rate of newborns in group QB、QC and QD was higher than that of group QA,group QD was higher than group QB,the difference was statistically significant( P<0. 05). Conclusion(1) Patients should be strictly selected,and expectant treatment should not be given blindly;(2) For patients with stable condition,expectant treatment should be carried out under strict supervision to improve neonatal outcome. However,whether expectant treatment should be given to patients under 28 weeks needs further study.

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Objective To investigate the differences of genomic DNA methylation in peripheral blood between asthmatic patients and healthy controls and its clinical significance. Methods 2 ml peripheral blood were collected from patients with acute exacerbation of asthma and healthy controls. After extracting peripheral blood DNA, the whole genome DNA methylation was detected by Illumina DNA methylation gene chip, and they were intersected with the 96 gene chip data samples in the download GSE56553 data set, then they were performed biological analysis on the functional pathways of different genes. Results There was a statistically significant difference in peripheral blood genomic DNA methylation between patients with asthma and healthy people. 1 493 differential genes were found, of which 923 were methylation-up-regulated genes and 570 were methylation-reduced genes.The differential genes obtained by functional enrichment analysis of GO and KEGG pathways were mainly involved in the processes of the regulation of synaptic signaling, muscle contraction, and cell adhesion. By constructing the gene interaction network, TNF, GNB1, PIK3 R1, CDC5 L, IL-10, CD44 and other 24 key genes were screened. Conclusion Differences in genomic DNA methylation between peripheral blood and healthy controls are statistically significant, and these differences may be the main causes of initiation and progression of asthma. The use of bioinformatics methods to screen out the key genes and signaling pathways in the development of asthma can provide new targets and strategies for asthma treatment.

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Objective To explore the predictive value of plasma heat shock protein 90α(HSP90α) and clinicopathologic features on epidermal growth factor receptor(EGFR) gene mutation in patients with non-small cell lung cancer. Methods The data of plasma Hsp90α, gender, clinical stage and the presence of metastasis in 89 newly diagnosed patients of non-small cell lung cancer(NSCLC) were collected, and the predictive value of those data on EGFR gene mutation was retrospectively analyzed. Results The mutation rate of EGFR gene in female, stage ⅢB～Ⅳ and metastasis patients(58.97%, 49.33% and 54.55%) was significantly higher than that in male, stage I～ⅢA and non-metastasis patients(32.00%,14.29% and 13.04%,P<0.05). The level of HSP90α in the EGFR mutant group was higher than that in the wild group(P<0.05). Combined detection of HSP90α, gender, clinical stage and metastasis increased the diagnostic sensitivity of EGFR mutations compared with each indicator alone(P<0.001). Conclusion The level of Plasma HSP90α combined with patients' gender, clinical stage and metastasis has a high clinical value in predicting EGFR mutation, and the combined detection can improve the diagnostic efficacy.

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Objective To explore the expression of adipocyte enhancer-binding protein 1(AEBP1) in glioblastoma(GBM) and its effect on the prognosis. Methods The expression of AEBP1 mRNA in GBM was analyzed by Oncomine database and GEPIA website. The GEPIA website and TCGA data were used to analyze the correlation between the expression level of AEBP1 mRNA and various clinicopathological features, as well as its influence on the prognosis of GBM. The expression of AEBP1 protein in glioma was further analyzed in the human protein atlas(HPA) database. Finally, the GO and KEGG analysis of AEBP1 and its co-expression genes were performed in WebGestalt website. Results All 7 data sets selected from Oncomine database and GEPIA website analysis showed that AEBP1 mRNA expression was up-regulated in GBM tissues, and the difference was statistically significant(P<0.01). The survival analysis of GEPIA website showed that the overall survival(OS) of patients with high AEBP1 mRNA expression reduced, and the difference was statistically significant(P=3.9×10-5). Further TCGA database analysis showed that AEBP1 mRNA expression level was correlated with IDH1 mutation(P=0.005), and it was an independent factor influencing the OS in patients with GBM(HR=0.563 1(0.390 2, 0.812 7),P=2.16×10-3). KEGG pathway enrichment analysis showed that AEBP1 and its co-expressed genes were mainly enriched in Hippo, NF-κB, TNF and other signaling pathways. Conclusion AEBP1 is highly expressed in GBM, and the high expression of AEBP1 mRNA is an independent prognostic factor for patients with GBM. Hippo, NF-κB, TNF and other signaling pathways may be the important pathway for AEBP1 overexpression to promote the occurrence and development of GBM. AEBP1 is a potential target for GBM patients.

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Objective To compare the fundus fluorescein angiography(FFA) and optical coherence tomography angiography(OCTA) in diabetic retinopathy(DR) in the diagnosis of characteristics, and to analyze the consistency in the detection of DR lesions between the two methods.Methods FFA and OCTA examination was carried out in 86 diabetic patients( 166 eyes),and 26 diabetic patients( 26 eyes) who had no eye fundus changes after FFexamination were included in the experimental group,and 15 patients( 25 eyes) with age and sex matching withofundus disease were selected as the control group for OCTA examination. Two examination images were obtainedas well as a series of parameters such as blood flow density of 300μm paracentral fovea( FD-300),central foveshallow layer,deep blood flow density and surrounding area of optic disc blood flow density. Results FFA waconsistent with OCTA diagnosis DR( Kappa = 0. 514,P<0. 001). Based on FFA,foveal avascular zone changwas found in 74 eyes,macular edema was found in 59 eyes,retinal microhemangioma was found in 138 eyes,retnal neovascularization was found in 112 eyes,nonperfused areas was found in 115 eyes. Based on OCTA,the above fundus diseases were found in 81,52,125,103,101 eyes,with no statistically significant difference( P 0. 05). Compared with the control group,the density of FD-300,the blood flow density in the shallow layer,thdensity of the blood flow in the central fovea concave depression and the surrounding area of optic disc decreasedwith statistically significant difference( P<0. 05). Conclusion FFA and OCTA were generally consistent in diagnosing diabetic retinopathy,while OCTA can detect the changes of partial blood flow parameters of DR without detecting macular and optic disc lesions in FFA,providing a new index for early DM patients without changes of fundus.

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Objective To study the expression and clinical significance of CD155 protein in pancreatic ductal adenocarcinoma tissues and adjacent normal tissues, as well as in pancreatic cancer cell lines. Methods Immunohistochemistry was used to detect the expression of CD155 in paraffin-embedded tissues and non-carcinoma adjacent tissues from 92 cases of pathologically confirmed pancreatic ductal adenocarcinoma.And the relationship between CD155 and clinical pathological parameters was analyzed. Western blot and qRT-PCR methods were also used to detect the expression of CD155 in normal pancreatic cells(HPDE6-C7) and three pancreatic cancer cells(Panc-1, BxPC-3, AsPC-1). Results The results of immunohistochemistry showed that CD155 was mainly expressed on the cell membrane of pancreatic ductal adenocarcinoma tissues. The positive expression rate of CD155 in pancreatic ductal adenocarcinoma tissues was 65.22%(60/92), while the positive expression rate in normal tissues adjacent to the cancer was 38.04%(35/92), the difference in positive expression between the two groups was statistically significant(χ2=13.60,P<0.01);The expression of CD155 was ralated to the degree of pancreatic ductal adenocarcinoma differentiation(P<0.001), neural infiltration(P<0.001), and lymph node metastasis(P=0.001); Westen blot and qRT-PCR results showed that the expression levels of CD155 protein and mRNA in three pancreatic cancer cells were higher than those in normal pancreatic cells, and the differences were statistically significant compared with normal pancreatic cells(P<0.01). Conclusion The expression of CD155 is correlated with the degree of pancreatic ductal adenocarcinoma differentiation, nerve invasion and lymph node metastasis. The detection of CD155 is used to evaluate the severity of pancreatic ductal adenocarcinoma patients. At the same time, CD155 is highly expressed in pancreatic cancer cells. It may be possible to use CD155 to bind to the immune cell activating receptor DNAM-1 to initiate the activation and killing effect of immune cells on pancreatic cancer and provide new ideas for immunotherapy of pancreatic cancer.

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The Influenza A H1 N1 suspected patients who underwent Influenza A H1 N1 influenza rapid antigen detection and RNA detection were incorporated into this study. All incorporated suspected patients were classified into 3 groups: single positive or negative group(antigen detection negative and RNA detection positive group), both negative group, both positive group. 44 normal persons without any disease who underwent healthy examination at the same time were selected as the control group. Univariate and multivariate analysis of White blood cells(WBC), Neutrophils(NEUT%), Lymphocyte(LYMPH%) and Monocyte(MONO%) were carried out to compare the statistical differences among these four groups. Meanwhile, receiver operating characteristic curves were drawn(ROC curve). The WBC and NEUT% of single positive or negative group were higher than both negative group(bothP<0.05), while the LYMPH% of single positive or negative group was lower than both negative group(P=0.023). There was no difference in these four factors between single positive or negative group and both positive group. The WBC and NEUT% of both negative group were lower than both positive group(bothP<0.05), while the LYMPH% and MONO% of both negative group were higher than both positive group(bothP<0.05). The WBC and NEUT% of single positive or negative group were higher than control group(bothP<0.05), while the LYMPH% of single positive or negative group was lower than control group(P<0.001). The WBC, NEUT% and MONO% of both negative group were higher than control group(bothP<0.05), while the LYMPH% of both negative group was lower than control group(P<0.001). The WBC and NEUT% of both positive group were higher than control group(bothP<0.05), while the LYMPH% and MONO% of both positive group were lower than control group(bothP<0.05). Based on the logistic regression analysis of single positive or negative group and both negative group, only WBC had statistical significance(P=0.010, HR: 1.51, 95%CI: 1.11～2.06). The area under ROC curve(AUC) of WBC in the diagnosis of false negative antigen detection was 0.890(95%CI: 0.79～0.99). The best cutoff value of WBC was 8.5×109/L. If the result of antigen detection is negative but the WBC is greater than or equal to 8.5×109/L, the RNA detection is needed to make the correct diagnosis.

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To investigate the clinical phenotype and ADAM10 mutated locus of reticular acral pigmentation in a Chinese pedigree. The clinical data of 54 people from 5 generations of RAK family were retrospectively analyzed,and some members of the family and 100 unrelated healthy control blood samples were collected. All exons of ADAM10 gene were amplified by PCR and sequenced. All the affected patients showed a network of freckle-like pigmentation spots distributed on the back and neck of the hands and feet. Transcoding mutations in the 4 th exon of ADAM10 gene( c. 425-426 del GA; p. R142 Ifsx2) were detected in the probands of this family and in all patients,which was not detected in normal control family members or in non-related normal controls. A new mutation of ADAM10 gene may lead to the truncation of the protein that it encodes,resulting in the occurrence of disease.

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58 patients with primary hepatic cancer and 24 patients with metastatic hepatic cancer were treated by transcatheter chemoembolization with drug-eluting beads microspheres. The curative effect of the two groups was evaluated by modified response evaluation criteria in solid tumors( mRECIST). The changes of liver function before and after treatment and the occurrence of postoperative complications were compared between the two groups. After a month treatment,the objective response rate( CR + PR) was 74. 14% in primary group,50. 00% in metastatic group; the disease control rate was 100. 00% and 75. 00% respectively. The difference was statistically significant( P<0. 05). The damage of liver function in the metastatic group was more serious than that in the primary group( P<0. 05). Complications were occurred in both groups. The incidence in the metastatic group was significantly higher than that in the control group. Transcatheter chemoembolization with Calli Spheres drug-eluting beads microspheres is safe and effective for hepatic cancer,and primary hepatic cancer is more accurate and safer than that of metastatic hepatic cancer.

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To summarize the diagnosis and treatment of acute renal failure caused by ureteral obstruction at different time. Retrospective analysis of 85 cases of acute renal failure caused by ureteral obstruction. The obstruction was successfully relieved in 85 cases, and the renal function was normal in 62 cases one week after operation. The decrease of urine volume, creatinine and urea nitrogen in 24 hours after operation in the group with obstruction≤1 week was significantly greater than that in the group with obstruction>1 week, and there were no dialysis patients;the number of positive cases in the group with obstruction≤1 week was significantly higher than that in the group with obstruction>1 week.The shorter obstruction time of acute renal failure caused by ureteral obstruction, the better prognosis after effectively removing the obstruction.