Abstract:Objective：To investigate the effect and mechanism of polyethylenimine （PEI） modified alumina hydroxide nanoparticles（HS/PEI） on enhancing dendritic cell （DC） antigen presentation. Methods：DCs were loaded with HS combined with ovalbum （OVA） antigen in the presence or absence of PEI and co-incubated with B3Z cells. The activation of B3Z cells was determined by CPRG assay. The expression of ubiquitinated OVA protein in DCs was detected by Western blot. After incubated with HS/PEI-OVA and different stimulants（IFN-α，R848），IL-12 expression of DCs was detected by ELISA，and the activation of B3Z cells was determined by CPRG assay after co-incubation with B3Z cells. DCs loaded with HS/PEI-OVA were co-incubated with CFSE-labeled OT-Ⅰ T cells to detect the proliferation of OT-Ⅰ T cells. The increased percentage of CD8+IFN-γ+T cells and IFN-γ secretion of specific T cells induced by DC-HS/PEI-OVA vaccine were examined in B16-OVA tumor-bearing mice. Results：Compared with HS without PEI，HS/PEI significantly enhanced the OVA antigen presentation ability of DCs，increased the ubiquitinated OVA protein expression and IL-12 secretion of DCs. IFN-α and R848 could further enhance the presentation of HS/PEI-OVA by DCs. HS/PEI-OVA could significantly promote OT-Ⅰ T cells proliferation in vitro and induce efficient T-cell responses in vivo. Conclusion：HS/PEI could enhance antigen cross-presentation of DCs and induce efficient T-cell responses.

Abstract:Objective：Taking advantage of the PiggyBac transposon system to generate a stable HeLa cell line that can inducibly express Cas9，and to construct a sgRNA library for human nuclear receptor genes to screen for cisplatin resistance genes. Methods： PB-TRE-Cas9-NLS-IRES-hrGFP-Zeo vector was constructed and transferred into HeLa cells together with PB-CAG-rtTA and the transposase vectors. Stable cell lines were obtained by drug screening and picking up single clones. Constructed the sgRNA virus library targeting nuclear receptor genes to infect the stable cell line，screened the clones resistant to cisplatin，and carried out the sequencing and identification of the target genes. Results：Five gene loci were edited efficiently in the stable cell line. Clones resistant to cisplatin were obtained after infection of sgRNA library，and most clones harbored VDR sgRNA and mutant VDR gene. Conclusion：Using PiggyBac transposon system，stable HeLa cell line with inducible expression of Cas9 was successfully constructed. The cell line can be used for efficient gene editing at multiple sites and high-throughput library screening for cisplatin resistance genes.

Abstract:Objective：To investigate the protective effects of ginkgo biloba extract（EGB761） on warfarin-induced calcification and osteogenic differentiation of aortic valve interstitial cell（AVIC）. Methods：Porcine AVICs were extracted，and alizarin red staining，intracellular calcium content and alkaline phosphatase activity were detected to analyze the effects of different concentrations of EGB761 on the calcification. The expressions of Runt-related transcription factor 2（Runx2），msh homeobox 2（Msx2），bone morphogenetic protein-2（BMP2）and phosphorylated Smad1/5 were detected by RT-PCR and Western blot. Results：Our results indicated that pAVICs from stimulation with warfarin increased calcium deposition and expression of osteogenic markers（Runx2，Msx2，and BMP2）and promoted phosphorylated-Smad1/5 from the cytoplasm to the nucleus. The addition of EGB761 significantly inhibited phosphorylated-Smad1/5 from the cytoplasm to the nucleus，thus，suppression calcification. Conclusion：EGB761 may reduce the phosphorylation level of Smad1/5 and inhibit the BMP2/Smad1/5/Runx2 signaling pathway，thereby alleviating the calcification and osteogenic differentiation of AVIC.

Abstract:Objective：To explore the protective effect of STF-08310，a specific inhibitor of inositol-requiring enzyme 1 endoribonuclease（IRE1）/spliced X-box binding protein 1（sXBP1）on liver ischemia-reperfusion（IR）injury and the possible mechanisms. Methods：Thirty C57BL/6 mice were randomly divided into 3 groups（10 in each group）：sham operation group（sham group），hepatic ischemia-reperfusion group（IR group），and STF-083010 pretreatment plus hepatic ischemia-reperfusion group（IR+STF-083010 group）. Levels of alanine aminotransferase（ALT） and aspartate aminotransferase（AST） in serum were detected by enzyme-linked immunosorbent assay（ELISA）. The histological damage of liver and the apoptosis of hepatocytes were evaluated by hematoxylin-eosin（HE） and TUNEL staining. The expression of interleukin（IL）-6，tumor necrosis factor（TNF）-α，and IL-1β mRNA were examined by RT-qPCR. sXBP1 and CHOP proteins in liver tissues were determined by immunohistochemistry and Western blot. Results：Compared to IR group，plasma ALT and AST levels in STF-083010+IR group were significantly lower（P < 0.01）. Liver tissues in STF-083010+IR group were more slightly damaged than those in IR group（P < 0.01）. The mRNA levels of IL-6，TNF-α and IL-1β in IR+STF-083010 group and the protein levels of sXBP1 and CHOP were significantly lower than those of IR group（P < 0.01）. Conclusion：Pretreatment of STF-083010 can alleviate liver IR injury by inhibiting sXBP1/CHOP signal pathway.

Abstract:Objective：To study the risk factors of patients with premature ST-segment elevation myocardial infarction（STEMI） and investigate the correlation between neutrophil gelatinase-associated lipocalin（NGAL） and premature STEMI and its clinical value in the prognosis assessment. Methods：Totally 166 patients diagnosed as premature STEMI from Jan 2017 to Dec 2018 were selected and followed up for 12 months，and 171 patients underwent coronary angiography during the same period with lumen stenosis <50% were selected as the control group. The risk factors of major adverse cardiac events（MACE） occurrence in premature STEMI patients were analyzed. Receiver operating characteristic（ROC） curve was used to find the optimal cutoff point for predicting the occurrence of MACE. Results：NGAL levels were significantly higher in premature STEMI group than those in control group（P < 0.05）. NGAL levels were significantly higher in MACE group compared with non-MACE group（P < 0.05）. Multivariate logistic regression analysis showed that NGAL was independently associated with MACE occurrence in premature STEMI patients（P < 0.05）. ROC curve of NGAL in predicting the occurrence of MACE showed that the area under curve of NGAL were 0.897（P < 0.05）. Conclusion：NGAL levels which were significantly elevated in premature STEMI patients are positively related with MACE occurrence. Thus NGAL can be used as a predictor of prognosis assessment in premature STEMI patients.

Abstract:Objective：To investigate the risk factors of coronary artery calcification（CAC）in maintenance hemodialysis（MHD）patients. Methods：A total of 188 stable MHD（≥3 months）patients were enrolled in the study，their baseline characteristics and laboratory measurements were collected，coronary artery calcification score（CACS）was measured by multi-slice computed tomography（MSCT），the risk factors for CAC were analyzed. Results：CAC（CACS>100）was present in 54.8%（103/188）patients，the median CACS was 143（0，728）. In comparison with the CACS<100 group，age，dialysis vintage，serum calcium，alkaline phosphatase（ALP）and intact parathyroid hormone（iPTH）levels were significantly higher than those in CACS≥400 group（P < 0.05）. Spearman correlation analysis revealed that CACS were positively correlated with age（r=0.292，P < 0.001），dialysis vintage（r=0.242，P=0.001），systolic pressure（r=0.167，P=0.024），serum calcium（r=0.263，P < 0.001），iPTH（r=0.191，P=0.009）and ALP（r=0.171，P=0.019）. With multivariate linear regression analysis，serum ALP was the only biomarker which showed significant correlation with CACS. Receiver operating characteristic（ROC） curve analysis showed that the area under curve（AUC） of ALP predicted severe CAC was 0.615（P=0.009），the optimal cutoff value was 226.5 U/L. By logistic regression analysis，serum ALP≥226.5 U/L was a robust predictor of CAC and was associated with the likelihood of CACS≥400（odds ratio 3.05，95% confidence interval 1.30 to 7.18，P=0.011）. Conclusion：Serum ALP level is a potential independent predictor of CAC in MHD patients. ALP is suggested to be a promising predictor and interventional target for cardiovascular calcification in MHD patients.

Abstract:Objective：To quantitative assess the effect of lipoprotein associated phospholipase A2（Lp-PLA2） level in predicting the severity of coronary lesions. Methods：A total of 123 patients who underwent coronary angiography and Lp-PLA2 detection were enrolled to evaluate Lp-PLA2 level in predicting acute coronary syndrome（ACS），multi-vessel lesions and SYNTAX Ⅱ score. Results：Lp-PLA2 was correlated with the diagnosis of coronary artery disease，multi-vessel lesions and SYNTAX Ⅱ score（all P < 0.05）. Lp-PLA2 had high sensitivity in predicting ACS（90.9%）and multi-vessel lesions（80.0%），high specificity in predicting SYNTAX Ⅱ score ≥23（81.7%）and ≥33（87.4%）. Lp-PLA2 was an independent risk factor for multi-vessel lesions and SYNTAX Ⅱ score ≥23 and ≥33（OR=1.004，1.003 and 1.004，respectively，all P < 0.05）. Subgroup analysis showed that the higher concentration of Lp-PLA2 predicted the higher risk of multi-vessel lesions in hypertension（OR=2.800，P < 0.05）and higher risk of SYNTAX Ⅱ score ≥23 in hypertension and diabetes patients（OR=3.586 and 18.000，respectively，both P < 0.05）. Conclusion：Lp-PLA2 can effectively predict the severity of coronary lesions，especially the sensitivity of ACS diagnosis and multi-vessel lesions and the specificity of SYNTAX Ⅱ score ≥23 and ≥33. The predictive value of Lp-PLA2 for coronary lesions is greater in hypertension and diabetes patients.

Abstract:Objective： To analysis the values of microvolt T-wave alternans（MTWA） and maximum T-wave alternans（max-MTWA）in patients with low or moderate risk coronary artery disease（CAD），and assess the risk of sudden cardiac death（SCD）. Methods：One hundred and twelve CAD patients were enrolled for this study，and sixty-six non-CAD patients as the control group. Based on the Duke treadmill test scores（DTS），CAD patients were divided into 2 groups：the low-risk CAD group（with scores ranging from 5 to 15）and the moderate-risk CAD group（with scores ranging from-10 to 5）. All participants performed treadmill exercise stress tests and MTWA，max-MTWA and the heart rates（HR） at max-MTWA were recorded by the time-domain modified moving average beat analysis（MMA）method，then the ratio of max-MTWA/HR was calculated. Results：There were significant differences in max-MTWA，max-MTWA/HR ratio and MTWA values between the control group and the CAD group（all P＜0.05）. Furthermore，subgroup analysis showed that the max-MTWA and max-MTWA/HR ratio in the moderate-risk CAD group were higher than those in the low-risk CAD group，and the parameters in the low-risk CAD group were higher than those in the control group（all P＜0.05）. There was no significant difference in MTWA between the low-risk CAD group and the control group（P＞0.05）. However，MTWA in the moderate-risk CAD group were significantly higher than those in the low-risk CAD group and the control group（all P＜0.05）. Conclusion：max-MTWA and max-MTWA/HR ratio were significantly increased in patients with severe CAD. The risk of SCD in low-risk CAD patients was the low as the control group，while moderate-risk CAD patients have a higher risk of SCD.

Abstract:Objective：The aim of this study is to compare the effect of biodegradable polymer drug-eluting stents（Firehawk）versus permanent polymer drug-eluting stents（Xience）on neointimal hyperplasia at one-year follow-up after percutaneous coronary intervention（PCI）from optical coherence tomography（OCT）observations. Method：This was a retrospective single center study，patients who had Firehawk/Xience stents during PCI in our center from January 2014 to June 2019 were included in the trial，and they were divided into two groups：Firehawk group and Xience group. At one-year follow-up，we compared the difference of in-stent neointimal hyperplasia from OCT observations between the two groups. Results：Totally 106 patients were finally enrolled，including 52 patients who were in the Firehawk group and 54 who were in the Xience group. There were no differences of clinical characteristics before PCI and at one-year follow-up between the two groups（P > 0.05）. There were no differences of parameters during PCI（target vessel，diameter and length of stent，pre-dilation and post-dilation，maximum diameter/pressure of dilated-balloons）between the two groups（P > 0.05）. At one-year follow-up，in-stent neointimal hyperplasia（maximum neointimal thickness，maximum neointimal area，minimum luminal area，minimum luminal diameter，restenosis rates and percentage of homogeneous property）was also similar between the two groups（P > 0.05）. Conclusion：It is similar of vascular response to biodegradable polymer drug-eluting stents and permanent polymer drug-eluting stents at one-year follow-up.

Abstract:Objective：To explore the application value of apolipoprotein A1（APOA1） and cholinesterase（CHE） in the diagnosis and severity of intrahepatic cholestasis of pregnancy（ICP）. Methods：This retrospective case-control study was conducted with 100 ICP patients and 100 normal pregnant women. Protein molecular markers APOA1 and CHE were compared between two groups. Results：APOA1 and CHE levels in the ICP group were significantly lower than those in the normal group（P＜0.05），the levels of two markers were negatively associated with that of total bile acids. The area under the receiver operating characteristic（ROC）curves（AUC）of APOA1 and CHE in diagnosis of ICP were 0.871 and 0.782，respectively，the AUC of APOA1 and CHE in severity of ICP were 0.843 and 0.773，respectively. Multiple logistic regression analysis showed that a combination of the levels of the two markers optimized the AUC to 0.909 and 0.891 in diagnosing ICP or evaluating the severity of ICP. Conclusion：Combined detection of APOA1 and CHE markers can be used as novel noninvasive biomarkers to evaluate the diagnosis and severity of ICP. The findings of this study can improve the diagnosis rate of ICP disease.

Abstract:Objective：To investigate the impact of ABVD（adriamycin，bleomycin，vinblastine，dacarbazine） chemotherapy regime on the testicular 18F-fluorodeoxyglucose（FDG） uptake in patients with Hodgkin’s lymphoma（HL）. Methods：Thirty-four patients at diagnosis monitored with 18F-FDG on positron emission tomography（PET）/computed tomography（CT） to assess treatment response for HL were selected for this retrospective analysis. The patients received ABVD chemotherapy regimen for six courses. The four 18F-FDG PET/CT examinations were performed at baseline and after every two courses of chemotherapy. Blood glucose，body weight，injection dose and injection time were collected，and the maximum standardized uptake value（SUVmax） of testis and mediastinal blood pool were measured. The changes of testicular 18F-FDG uptake in patients with HL after four 18F-FDG PET/CT examinations were analyzed. Results：There were statistical significance in testis SUVmax and weight（P=0.017，0.001） at four PET/CT examinations for 34 cases with HL. Compared with the testicular SUVmax at the first PET/CT examination，the testicular SUVmax at the second time decreased by 0.998，P=0.045. There were no significant differences in testicular SUVmax between the last two time points and the first time or over the course of chemotherapy（P＞0.05）. The testis SUVmax were found to be positively correlated with mediastinal blood pool SUVmax at the first PET/CT examination（baseline）（r=0.51，P=0.002），but not with age（P=0.646）. The weight at last three PET/CT was higher than at the first time（P=0.009，0.004，0.016），but no changes were found during at last three PET/CT examinations（P > 0.05）. Conclusion：For patients undergoing ABVD chemotherapy regime for Hodgkin’s lymphoma，the testicular 18F-FDG uptake decreased temporarily over the course of chemotherapy，but recovered in the later. Therefore，ABVD chemotherapy regime may have little effect on testicular glycometabolism of patients with Hodgkin’s lymphoma.

Abstract:Objective：To evaluate risk factors for the occurrence of cement leakages after percutaneous kyphoplasty for osteoporotic vertebral fractures. Methods：A total of 252 vertebrae with percutaneous kyphoplasty were investigated. The following 17 parameters were evaluated：patient age，sex，and so on. The influence of possible risk factors affecting cement leakage was assessed using univariate analysis，and the parameters with statistical significance were incorporated into the multivariate logistic regression model，and the prediction model was established. The AUC value of ROC was used to evaluate the value of diagnostic tests. Results：The presence of intravertebral cleft，cortical disruption，large volume of cement and low bone mineral density were selected with statistical significance by univariate analysis for cement leakage in general. Multivariate logistic regression showed that the presence of cortical disruption（P=0.001），large volume of cement（P=0.047） and low bone mineral density（P=0.002） were independent predictors for cement leakage. The combined prediction model of cement leakage was established. The AUC value was 0.751，the sensitivity was 61.0%，and the specificity was 82.5%. Conclusion：The presence of cortical disruption，large volume of cement and low bone mineral density of treated level are three independent risk factors for cement leakage after percutaneous kyphoplasty for osteoporotic vertebral fractures，and the combined prediction model has excellent prediction efficiency.

Abstract:Control of cholesterol levels can reduces the incidence of atherosclerotic cardiovascular disease（ASCVD）. Increased low-density lipoprotein cholesrerol has been an independent risk factor of ASCVD. Statins，cholesrerol absorption inhibitor，bile acid sequestrant have been proved effectively for reduction of low-density lipoprotein cholesterol. New type therapeutic drugs proprotein convertase subtilisin/kexin type 9 inhibitors，microsomal triglyceride transfer protein inhibitor，antisense oligonucleotide inhibitors，peroxisome proliferator-activated receptor-α have also achieved clinical benefit in recent clinical trials. In this article，we will review the efficacy and safty of cholesterol-lowering drugs，so that we can find out the most effective plan of cholesterol management.

Abstract:Long non-coding RNA（lncRNA） is a kind of nucleic acid molecule which is transcribed from the mammalian genome and lacks protein-coding potential，it mainly realizes the regulation of gene expression from three aspects of epigenetics，transcriptional regulation and post-transcriptional regulation，or directly participates in regulating protein activity. With the development of sequencing technology，it has been found that lncRNA can be used as miRNA sponge to further regulate mRNA expression，and the lncRNA-miRNA-mRNA axis plays an important role in the pathogenesis of diseases. Current researches confirm that the lncRNA-miRNA-mRNA axis is closely related to the pathogenesis of cardiovascular diseases. In this review，we summarize the latest developments in the known roles of this axis in the pathogenesis of cardiovascular diseases.

Abstract:In recent years，C1q/tumor tumor necroscs factor-related protein（CTRP） plays an important role in the pathophysiology of various cardiovascular diseases such as atherosclerosis，ischemic cardiomyopathy and hypertension. CTRP family members including CTRP1，CTRP3，CTRP5，CTRP9，CTRP12 and CTRP13 can affect the development of coronary artery disease（CAD）by regulating immune inflammation，glucose and lipid metabolism，and endothelial function.