Abstract:Objective：To assess the variability and reproducibility of patch clamp platforms/sites for defining clinical drug effects on human ether-à-go-go related gene（hERG） currents across and between platforms and sites and to investigate the blocking effect of nine clinical drugs that have high（bepridil，quinidine，sotalol），intermediate（ondansetron，cisapride，terfenadine）and low（ranolazine，verapamil and mexiletine）torsade de pointes risk（TdP）on hERG potassium channel. Methods：The whole-cell patch clamp technique was used to record the change in hERG potassium current（IKr）on HEK293 cells that stably expressed hERG potassium channel（hERG-HEK293 steady-state cells），which was treated with four test concentrations of bepridil，quinidine，sotalol，ondansetron，cisapride，terfenadine，ranolazine，verapamil and mexiletine，to study the concentration-dependence of the effects on IKr and the half maximal inhibitory concentration（IC50）. Resuts：All of the nine clinical drugs tested produced a concentration-dependent reduction of hERG current. The IC50 values of bepridil and quinidine（high TdP risk clinical drugs） were about 98.32 nmol/L and 1.95 μmol/L，respectively，and the IC50 values of sotalol was >300 μmol/L. The IC50 values of ondansetron，cisapride，terfenadine（intermediate TdP risk clinical drugs）were 0.94 μmol/L，39.10 nmol/L，128.58 nmol/L，respectively. The IC50 values of ranolazine，verapamil and mexiletine（low TdP risk clinical drugs）were 9.94 μmol/L，235.49 nmol/L and 65.56 μmol/L，respectively. The IC50 values for the nine clinical drugs corresponded well to those published within the literature. Conclusion：The risk of drug-induced TdP is closely related to the block of the hERG channel，but the hERG channel block is lack of specificity as a predictor of TdP，which is also associated with multiple ion channel effects. Some clinical drugs also block Nav1.5-late and/or Cav1.2 currents，which can reduce the risk of TdP caused by hERG block. The data obtained by this method is reliable，which provides a reference for the hERG block test performed by domestic GLP laboratories and can be used for the safety evaluation of drug cardiac toxicity.

Abstract:Objective：To construct luciferase reporter plasmids of full-length and truncated promotors of rat macrophage inflammatory protein-1α（MIP-1α）gene and detect their activity in HEK-293T cells in response to interferon regulatory factor-8（IRF-8）overexpression，screening the possible binding elements for IRF-8. Methods：Rat MIP-1α promoter was amplified by PCR and cloned into the luciferase reporter plasmid（pGL3-basic）. The recombinant plasmid（pGL3-MIP-1α-FL）and rat IRF-8 overexpression plasmid（pIRES2-IRF-8）were co-transfected into HEK-293T cells and then the luciferase activity was detected to determine the role of IRF-8 in MIP-1α gene transcription. Meanwhile，the potential IRF-8 binding elements within MIP-1α promoter were predicted by using bioinformatics software. Based on the predicted results，three luciferase reporter plasmids of truncated MIP-1α gene promotor（pGL3-MIP-1α-1~3）were constructed. The promoter luciferase reporter plasmids of pGL3-MIP-1α-FL or pGL3-MIP-1α-1~3 and the plasmid of pIRES2-IRF-8 were co-transfected into HEK-293T cells. Then，the luciferase activity was detected to screen the IRF-8 binding elements. Results：It was verified that pGL3-MIP-1α-FL（-1 400~+94 nt）plasmid was constructed correctly by PCR analysis and nucleotide sequencing. The plasmids of pGL3-MIP-1α-FL and pIRES2-IRF-8 were co-transfected into HEK-293T cells，and then the luciferase activity of MIP-1α gene promotor was markedly increased in response to IRF-8 overexpression. The potential IRF-8 binding elements（-1 157~ -1 144 nt，-740~ -734 nt，-683~ -670 nt，-365~-359 nt，and -249 ~ -236 nt）within MIP-1α promoter were predicted by using bioinformatics software. Based on the predicted results，we constructed three luciferase reporter plasmids of truncated MIP-1α gene promotor，namely pGL3-MIP-1α-1（-453 ~ +94 nt），pGL3-MIP-1α-2（-352 ~ +94 nt）and pGL3-MIP-1α-3（-3 ~ +94 nt）. The plasmids of pGL3-MIP-1α-FL or pGL3-MIP-1α-1~3 and pIRES2-IRF-8 were co-transfected into HEK-293T cells，and the result displayed that the activity of pGL3-MIP-1α-3 was much lower than that in pGL3-MIP-1α-FL，pGL3-MIP-1α-1 and pGL3-MIP-1α-2，indicating that the region of rat MIP-1α promoter（-352 ~ -3 nt）might contain an IRF-8 binding element（-249 ~ -236 nt）. Conclusion：The rat full-length and truncated rat MIP-1α promotor luciferase reporter plasmids were constructed successfully，and the possible IRF-8 binding element was found，which could be beneficial to further studies.

Abstract:Objective：To explore the proliferation effect of long noncoding RNA（LncRNA）AGAP2-AS1 on colorectal cancer（CRC）cell lines and the associated signaling pathways. Methods：We conducted qRT-PCR to investigate mRNA levels of AGAP2-AS1 in 50 paired CRC tissues and the corresponding normal mucosa tissues. SiRNA targeting AGAP2-AS1 was transfected into DLD-1 and HT29 cell lines，qRT-PCR was performed to detect the transfection efficacy of siRNA and AGAP2-AS1 downregulated DLD-1 and HT29 cells were used for further investigating the role of AGAP2-AS1 in CRC cell proliferation through CCK8-kit and colony formation assay. Cell cycle distributions were analyzed by a flow cytometer. Western blot was conducted to explore the protein levels of MAPK signaling pathway，including Ras，Raf-1，MEK and ERK. Results：The mRNA levels of AGAP2-AS1 were markedly upregulated in CRC tissues rather than the corresponding normal tissues. Loss of AGAP2-AS1 greatly suppressed cell proliferation of DLD-1 and HT29 cells，increased percentage of G0/G1 phases population and downregulated the protein levels of Ras，p-Raf-1，p-MEK and p-ERK. Conclusion：LncRNA AGAP2-AS1 could promote colorectal cancer cell proliferation through Ras/MAPK signaling pathway.

Abstract:Objective：To construct the recombinant eukaryote expression vector containing Max dimerization protein 1（Mad1）gene and detect its effect on gastric cancer cell proliferation and migration. Methods： The Mad1 gene was cloned into pEGFP-N1 expression vector by recombining DNA technology. The recombinant vector was identified by restriction enzyme analysis and nucleotide sequence determination. The eukaryotic expression plasmid pEGFP-N1-Mad1 was transiently transfected into AGS cells. Expression of Mad1 gene and protein was identified by RT-PCR and Western blot，respectively. The location of Mad1 protein was detected by fluorescence microscope. The proliferation and migration of AGS cells were examined by CCK-8 and Transwell assay，respectively. Results：The Mad1 gene was successfully cloned to the eukaryote expression vector pEGFP-N1. Expression of Mad1 gene and protein was confirmed by RT-PCR and Western blot. After transfection，Mad1 could be detected in the nucleus of AGS cells. CCK-8 and Transwell experimental results showed that the proliferation and migration of pEGFP-N1-Mad1 transfected cells were deteriorated significantly compared to empty vector transfected AGS cells and normal AGS cells. Conclusion：The new recombinant expression vector pEGFP-N1-Mad1 was constructed and expressed successfully in AGS cells. Mad1 could inhibit the proliferation and migration of gastric cancer cells.

Abstract:Objective：To investigate the expression of ANLN in intrahepatic cholangiocarcinoma（ICC）and explored the function of ANLN in proliferation of ICC in vivo. Methods：We used the Western blot and real-time PCR（RT-PCR）to quantify the expression of ANLN in cancerous tissues and adjacent tissues of 40 patients with ICC. The differences in the expression of ANLN in ICC and the adjacent tissues of cancer were compared，and its relationship with tumor staging and tumor size was analyzed. ANLN low expression HUCCT1 cell lines were established using small interference RNA（siRNA）. The cell proliferation was investigated by cell counting kit-8 assay（CCK-8），colony formation and cell cycle arrest. In addition，the proteins that regulate ANLN expression in CCA were selected by using String，and the relationship between them was verified by Western blot and RT-PCR. Results：The results of Western blot and RT-PCR revealed that ANLN was highly expressed in ICC tissues. Clinical data analysis showed that the expression of ANLN was closely related to the tumor size and TNM stage in patients with cholangiocarcinoma，and the prognosis of patients with high ANLN expression was poor. The reduction of ANLN by siRNA could effectively inhibit the proliferation ability of cholangiocarcinoma cells. Western blot showed that the reduction of ANLN led to a significant decrease in the expressions of periodic protein cyclin D1 and cyclin A. String showed that TPX2 may play a major role in the regulation of ANLN expression，Western blot and RT-PCR further validated the positive relationship between ANLN and TPX2. Conclusion：ANLN regulates the proliferation of cholangiocarcinoma cells，which promotes the development of ICC and provides a new target for the treatment of ICC.

Abstract:Objective：To analyze the effect and mechanism of verbascoside on the migration and invasion of oral squamous cell carcinoma. Methods：The expression profiles of HN4 protein in oral squamous cell carcinoma cells treated with verbascoside and the blank control group were analyzed by mass spectrometry. Proteins with high abundance and significantly increased expression after verbascoside treatment were screened. The results of mass spectrometry were verified by Western blotting. The expression of key proteins in HN4 cells was interfered by shRNA to analyze verbascoside. Effects of verbascoside on migration and invasion of squamous cell carcinoma HN4 cells were analyzed. Results：The results of mass spectrometry analysis showed that 18 proteins，including Max，MPRSS11F，ROBO4，AP4E1，and etc，was significantly increased in oral squamous cell carcinoma HN4 cells after treatment with verbascoside（fold change>1.5）. The Max proteins with the most obvious changes were detected by Western blotting. The results of Western blotting were consistent with those of mass spectrometry microarray. shRNA interfered with the expression of Max in oral squamous cell carcinoma HN4 cells. qRT-PCR and Western blotting showed that the expression of Max in HN4 cells was significantly down-regulated. Further stimulation of HN4 cells with verbascoside showed that the migration and invasion of HN4 cells were significantly inhibited. However，the ability of verbascoside to inhibit the migration and invasion of HN4 cells decreased significantly after knockdown of Max protein. Conclusion：It is possible that verbascoside inhibits the migration and invasion of oral squamous cell carcinoma cells by enhancing the expression of Max in oral squamous cell carcinoma cells.

Abstract:Objective：To establish a sodium taurocholate cotransporting polypeptide（NTCP）-complemented Huh7.5.1 cell line（Huh7.5.1-hNTCP）that supports hepatitis B virus（HBV） and hepatitis C virus（HCV） co-infection. Methods：Huh7.5.1 cells were infected with GV358 recombinant lentiviral vector carrying human NTCP encoding gene，green fluorescent protein（GFP）gene and puromycin resistance gene with the multiplicity of infection（MOI）of 50. NTCP positive cells were obtained through the puromycin screening and NTCP expression was identified by Western blotting. Huh7.5.1-hNTCP cells were infected with HBV derived from HepAD38 cells. The expression of HBsAg，HBeAg and HBV DNA at different time points were detected by ELISA and qPCR. HCV-JFH1 was added 24 hours after HBV infection，and then HBV DNA and HCV RNA were detected in co-infected cells. Results：Western blotting results indicated that Huh7.5.1-hNTCP cell line stably expressed the HBV receptor NTCP. ELASA and qPCR results showed that HBsAg，HBeAg and HBV DNA secretion increased gradually and peaked on the 9th day in HBV infected Huh7.5.1-hNTCP cells. The results of qPCR suggested that the replication of HBV DNA and HCV RNA increased gradually at different time points in HBV and HCV co-infected cells. Conclusion：Huh7.5.1-hNTCP cell line was established，and it can be co-infected by HBV and HCV.

Abstract:Objective：To test potential therapeutic effects of bisphosphonate nanoemulsion（BP nanoemulsion）in the experimental autoimmune neuritis（EAN）. Methods：In vitro BP nanoemulsion treatment was performed in macrophage cell line RAW264.7，real-time PCR（RT-PCR）was used to evaluate the expression of inflammatory factors interleukin（IL）-1β，IL-6，inducible nitric oxide synthase（iNOS），anti-inflammatory factor IL-10 and macrophage M2 marker CD206. After successfully establishing EAN rats model，BP nanoemulsion treatment was given，weight change of rats was assessed. The mechanical pain threshold and clinical score were analyzed. Luxol fast blue（LFB）staining was applied to show sciatic myelinopathy. Inflammatory cell infiltration and pathological changes in the sciatic nerve were evaluated by immunohistochemistry. The expressions of inflammatory cytokines IL-1β，IL-17，iNOS and matrix metalloproteinase 9（MMP-9）mRNA level in sciatic nerve were detected by RT-PCR. Results：BP and BP nanoemulsion treatments inhibited IL-1β and iNOS，increased the expressions of IL-10 and CD206，and induced phenotypic switch of macrophage polarization from M1 to M2 subtype in cell culture. In EAN rats：BP nanoemulsion ameliorated body weight loss and neurological signs，ameliorated mechanical allodynia，shortened disease duration，reduced myelin lesions. Meanwhile，it inhibited accumulation of macrophages and other immune cells，and decreased expressions of inflammatory cytokines IL-1β，IL-17，iNOS，and MMP-9 mRNA level in sciatic nerves of EAN rats. Conclusion：BP nanoemulsion can reduce accumulation of immune cells and attenuated inflammatory cytokines in sciatic nerves，and improve the clinical pathological changes of EAN rats. BP nanoemulsion may therefore be considered a potential therapeutic option for neuroinflammatory diseases.

Abstract:Objective：To investigate the effect of baicalin on the expression of inflammatory cytokines in human periodontal ligament fibroblasts （HPDLFs） induced by lipopolysaccharide（LPS）. Methods：After the cultured HPDLFs were treated with different concentrations of baicalin，the cytotoxicity of different concentrations of baicalin on HPDLFs was observed by CCK8. The cultured HPDLFs were divided into the blank control group，the baicalin group，the LPS group，and the LPS + baicalin group. The blank control group only added 2% fetal bovine serum culture solution；the baicalin group added 200 or 500 ng/mL baicalin，respectively；the LPS group added 100 μg/mL LPS；the LPS + baicalin group added 100 μg/mL LPS，and 200 or 500 ng/mL baicalin，respectively. Cells were collected 24 h later. The changes of IL-6，IL-8，and IL-1β mRNA expressions in each group were examined. Results：The results of the CCK8 experiment show that the addition of baicalin to the cells at a concentration of 500 ng/mL had no significant cell proliferation toxicity. There was no significant change in the expression of IL-6，IL-8 and IL-1βcompared with the baicalin group of baicalin 200 ng/mL and 500 ng/mL（P＞0.05）. Compared with the blank control group，the expression of IL-6，IL-8 and IL-1β in the LPS group increased significantly（P < 0.05）. At the same time，when LPS + 200 ng/mL baicalin were added，the expression of IL-6，IL-8 and IL-1β were significantly decreased compared with LPS alone（P < 0.05）. When LPS + 500 ng/mL baicalin were added，the expression of IL-6，and IL-1β were significantly increased compared with LPS alone（P < 0.05）. Conclusion：Baicalin showed anti-inflammatory effect at a low concentration，and showed pro-inflammatory effect when the concentration increased to 500 ng/mL.

Abstract:Objective：To study the phenotypic and genotypic distribution of Acinetobacter baumannii in Yizheng area to carbapenem drug resistance，and to explore the main mechanism of carbapenem resistance of Acinetobacter baumannii. Methods：The clinical isolates of Acinetobacter baumannii were divided into two groups according to the results of routine drug sensitivity test. Twenty-five strains of extensively drug-resistant Acinetobacter baumannii（XDRAb）and 23 of common strains were selected to detect metal β-lactamases by modified EDTA disk synergy method. Carbapenem was detected by carbapenem inactivation method，chromosome and plasmide-mediated AmpC enzyme were detected by double disk synergy test and modified three dimensional test，and the resistant genes blaOXA-23，blaOXA-24，blaTEM，blaAmpC，blaVIM，and blaNDM-1 were detected by PCR method，and some positive products were sequenced and compared. Results：The XDRAb group and the common group accounted for 62.5% and 37.5%，respectively. One strain of metal β-lactamase，4 strains of carbapenemase，and 1 strain of chromosome and 23 strains of plasmide-mediated AmpC enzyme were positive in the XDRAb group，but none of them were detected in the common group. The genes blaOXA-23，blaTEM，and blaAmpC were detected in all strains of XDRAb，and blaOXA-24，blaVIM，and blaNDM-1 were not detected in all of them. In the normal group，4 strains of blaOXA-23，5 strains of blaOXA-24，22 strains of blaTEM and 12 strains of blaAmpC were detected respectively，while blaVIM and blaNDM-1 were not detected in all strains. The difference of plasmid mediated AmpC enzyme，blaOXA - 23，and blaAmpC gene carrying rate between the two groups was statistically significant（χ2=40.627，34.183，15.511，P < 0.001，respectively）. The results of gene sequencing showed that the sequence of some strains was changed by base insertion or replacement. Conclusion：The drug resistance of Acinetobacter baumannii to carbapenem is serious in Yizheng area. The main mechanisms of Acinetobacter baumannii resistance to carbapenem are plasmide-mediated AmpC enzyme，blaOXA-23 and blaAmpC gene mediated drug resistance.

Abstract:Objective：Matrix-assisted laser desorption/ionization-time of flight mass spectrometry（MALDI-TOF MS）was performed to detect the homology of carbapenem-resistant Klebsiella pneumoniae（CRKp）. Compared with pulsed field gel electrophoresis（PFGE）and multilocus sequence typing（MLST），the application value of mass spectrometry in daily work was discussed. Methods：Ten strains of Klebsiella pneumoniae isolated from patients in our hospital from October 2017 to December 2017 and collected from ICU environment were collected. Eight resistant genes（blaTEM，blaSHV，blaCTX-M，blaKPC，blaIMP，blaNDM，blaVIM，and blaOXA）were detected. The homology of these strains was analyzed by PFGE，MLST and mass spectrometry（MALDI-TOF MS），and the results were compared. Results：It was confirmed that 10 strains of CRKp were all of the same cloned strains by PFGE，the ST-type of ST11. MALDI-TOF MS could be distinguished from different strains of Klebsiella pneumoniae by cluster analysis and principal component analysis. The homology of the same type of Klebsiella pneumoniae was about 80%. Conclusion： MALDI-TOF MS can be used in the detection of the homology of Klebsiella pneumoniae in nosocomial local infection，which is consistent with the results of PFGE and MLST. But it is necessary to establish the standard judgment standard as soon as possible.

Abstract:Objective：To study the expression level of pyruvate dehydrogenase kinase 1（PDK1）in ovarian cancer（OC）tissues and its correlation with clinicopathological characteristics and prognostic factors. Methods：Real time PCR was used to detect the mRNA expression of PDK1 in ovarian cancer cell line SKOV3 and human ovarian epithelial cell line HOSEpiC. Real time PCR was used to detect the mRNA expression levels of PDK1 in patients with benign ovarian tumor（BOT）and ovarian cancer. Immunohistochemistry was used to detect the expression of PDK1 in ovarian benign tumors and ovarian cancer tissues. Univariate and multivariate logistics regression analysis was used to analyze the relationship between PDK1 expression and OC clinicopathological characteristics，and survival analysis was performed by Kaplan-Meier. Results：The average expression level of PDK1 mRNA in the ovarian cancer cell line SKOV3was significantly higher than that of human ovarian epithelial cell line HOSEpiC（t=38.60，P＜0.001）. The average expression level of PDK1 mRNA in ovarian cancer tissues was significantly higher than that in ovarian benign tumor tissues（t=2.411，P=0.022）. The immunohistochemical staining showed that the average expression level of PDK1 protein in the ovarian cancer tissue was significantly higher than that of the benign ovarian tumor tissue（χ2=33.874，P＜0.001）. The high expression of PDK1 was obviously associated with lymph node metastasis by univariate and multivariate logistics regression analysis，and had no significant correlation with age，tumor size，tumor differentiation，unilateral bilateral onset，and the completeness of the envelope. Furthermore，lymph node metastasis is an independent risk factor affecting PDK1 expression in ovarian cancer tissues. Patients with high expression of PDK1 had poor prognosis（χ2=4.455，P=0.035）. Conclusion：PDK1 is highly expressed in ovarian cancer tissue，as an inhibitory enzyme of pyruvate dehydrogenase（PDH），PDK1 is involved in the process of tumor cell metabolism and recombination，and may play a pivotal role in the progress of ovarian cancer. It also can be used as a reference index to judge the poor prognosis of ovarian carcinoma.

Abstract:Objective：To investigate the clinical value of PAX5 promoter methylation as a biomarker of prostate cancer. Methods：The expression of PAX5 mRNA in prostate cell lines（RWPE-1，LNCaP，PC-3，and DU145）was detected by real time RT-PCR. Methylation-specific PCR（MSP）was used to analyze the methylation status of four prostate cells Real-time RT-PCR was used to detect the expression of PAX5 mRNA in tumor cells. Real-time MSP was used to detect the expression of PAX5 gene in 64 cases of prostate cancer，22 cases of benign prostatic hyperplasia and 47 healthy controls. The methylation level of PAX5 gene promoter in the serum of patients with prostate cancer was analyzed by ROC curve. The methylation level of PAX5 gene promoter in the serum of patients with prostate cancer was analyzed statistically. Results：Real-time RT-PCR showed that PAX5 mRNA was down-regulated in three prostate cancer cells compared with normal prostate epithelial cell RWPE-1；PAX5 gene promoter was detected in LNCaP，PC-3 and DU145 prostate cancer cells. Methylation of PAX5 gene promoter in normal prostate epithelial cell RWPE-1；the expression of PAX5 gene mRNA was restored by demethylation drug；Real-time MSP result showed that the methylation level of serum PAX5 gene promoter of prostate cancer patient was significantly higher than that of benign prostatic hyperplasia patients and healthy subjects. The methylation rate of PAX5 gene promoter was correlated with Gleason score and TNM staging；ROC results showed that the diagnostic value of PAX5 gene was superior to that of PSA. Conclusion：The methylation status of PAX5 gene in prostate cancer cells is the main reason for the down-regulation of PAX5 gene expression. Methylation of PAX5 promoter is a potential marker for prognosis of prostate cancer.

Abstract:Objective：The study aimed to evaluate effects of enteral nutrition on proton pump inhibitors（PPI）-caused adverse gastrointestinal reactions in critically ill patients. Methods：As a cross-sectional study，the study involved all hospitalized patients in the ICUs of 100 hospitals all over the country on April 25th，2017（patients newly admitted on April 25th were excluded）. Self-designed questionnaire items and a standard questionnaire were used. The self-designed questionnaire was composed by patient’s general profile，administered drugs and treatment，nutrition administration，feeding intolerance evaluation and lab test results，while the standardized questionnaire included body mass index（BMI），grade of acute gastrointestinal injury（AGI），sepsis-related organ failure（SOFA）score and acute physiology and chronic health evaluation Ⅱ（APACHEⅡ）score. Single factor analysis was used to investigate whether PPIs could affect gastrointestinal function in patients. Multivariate logistic regression models were performed to investigate whether enteral nutrition has an effect on AGI. Results：①Among the 508 patients who were not given enteral nutrition，a total of 401 patients（78.9%）used PPIs，while the rest 107 patients（21.1%）did not. AGI Grade 4 and Grade 2-3 cases accounted for 3.8% and 17.0% of patients with PPIs treatment，which was significantly higher than that（1.9% and 9.3%，respectively）of non-PPIs groups（P=0.027）. ②Among the 1，138 patients with PPIs administration，724 patients（63.6%）had started enteral nutrition，their AGI score（10.5%，Grade 2-3；0.7%，Grade 4）was superior to the rest 401 cases（35.2%）without enteral nutrition（17.0%，Grade 2-3；3.8%，Grade 4；P < 0.001）. However，the two groups suggested no statistically significant difference in 28-day prognosis. According to the result of multivariable logistic regression，enteral nutrition was an independent protection factor for gastrointestinal function（OR=0.353，95% CI：0.242-0.513，P < 0.001）. Conclusion：Enteral nutrition has an association with protecting ICU patients against PPI-caused adverse reactions of gastrointestinal dysfunction and it does not reduce the death rate.

Abstract:Objective：To observe the evolution of pulmonary artery diameters and cardiac functional changes in a rat model of pulmonary artery hypertension（PAH）using 7.0T cardiac magnetic resonance（CMR）. Methods：A rat model of PAH was established by hypoxia. A total of 36 rats were divided into 6 groups on average（baseline，hypoxia at 1st，2nd，3rd，4th，and 5th weeks；n=6）. CMR was performed every week by Bruker BioSpec 7.0T. The diameters of the main pulmonary artery（MPA），right pulmonary artery（RPA），left pulmonary artery（LPA），right ventricular end-diastolic maximum diameter（dRVmax），left ventricular end-diastolic maximum diameter（dLVmax），right ventricular end-diastolic volume（RVEDV）and right ventricular end-systolic volume（RVESV）were measured on MR images；ratio of dRVmax to dLVmax（dRVmax/dLVmax），ratio of the main pulmonary artery to the ascending aorta（MPA/AA，RPA/AA，and LPA/AA），right ventricular and left ventricular ejection fraction（RVEF）were calculated. Right ventricular systolic pressure（RVSP）was obtained by right heart catheterization after CMR imaging for each rat. Comparison of above-mentioned parameters at different time points was calculated by t test and ANOVA analysis（SPSS 24.0）. Pearson correlation analysis was used to evaluate the correlation between above-mentioned parameters and RVSP. Results：The RVSP in model rats at the first week increased significantly compared with the baseline［（29.92 ± 1.94）mmHg vs.（41.55 ± 3.14）mmHg，P＜0.01］，and then gradually increased from the first week to the fifth（P < 0.01）. MPA，dRVmax/dLVmax，RVESV，and RVEDV gradually increased（P＜0.01）. RVEF decreased significantly in the 2nd week of modeling（P < 0.01）. There were moderate correlations between the MPA/AA，dRVmax/dLVmax，RVEF and RVSP in model rats（r=0.573，r=0.700，r=-0.760，all P < 0.01）. Conclusion：7.0T CMR can sensitively observed changes in pulmonary artery diameter and right ventricular function during the progression of PAH rats，which lays a foundation for studying the evolutionary mechanism of PAH.

Abstract:Objective：To assess the structure and function remodeling of left atrial（LA）and left atrial appendage（LAA）using cardiac CT in patients with atrial fibrillation（AF），and to evaluate its relation with stroke. Methods：We retrospectively analyzed the CT imaging of 221 patients with AF and divided them into the stroke group and the non-stroke group. The left atrium maximum volume（LAVmax），left artium minimum volume（LAVmin），left artrium appendage maximum volume（LAAVmax）and left artrium appendage minimum volume（LAAVmin）were segmented and measured by post-processing software. The LA and LAA ejection fractions（LAEF，LAAEF）and LAA were calculated. According to the shape of the appendage，we divided LAA into chicken wings and non-chicken wings. And whether there was a thrombus or circulatroy stasis in LAA was also observed. Univariate and multivariate statistical analyses were carried out on the parameters of LA. Results：Among the 221 patients with AF，47 patients developed a stroke. The LAVmax and LAVmin in the stroke group were significantly larger than those in the non-stroke group（P < 0.05），LAEF in the stroke group decreased compared with the non-stroke group（P < 0.05）. The proportion of non-chicken wing type in the stroke group was higher than that in the non-stroke group（P=0.006）. The proportion of thrombosis or pre-thrombotic state in the LA of the stroke group was higher than that in the non-stroke group（P=0.01）. The LA volume，LAA structure，and LAA hemodynamic status were independently associated with stroke. Conclusion：LA parameters measured by cardiac CT may be useful for predicting stroke in patients with AF.

Abstract:Objective：To investigate the clinical value of quantitative measurements of extraocular muscles with T2 mapping in the diagnosis and staging of thyroid-associated ophthalmopathy（TAO）. Methods：Thirty-six patients with TAO and 28 healthy controls（HCs）were enrolled in our study and evaluated using T2 mapping imaging. The hotspot T2 relaxation time（T2RT）values of the most inflamed extraocular muscles were measured，and compared between the TAOs and the HCs groups，as well as the active TAOs and the inactive TAOs groups. Receiver operating characteristic（ROC）analysis was performed to evaluate the diagnostic value of T2RT for discriminating active TAOs from inactive TAOs. Results：The T2RT values of extraocular muscles in TAOs were significantly higher than those in HCs（P < 0.001）. The T2RT values of extraocular muscles in active TAOs were significantly higher than those in inactive TAOs（P < 0.001）. ROC results indicated that，optimal staging efficacy（area under the curve，0.863；sensitivity，75.0%；specificity，93.8%）for differentiating active TAOs from inactive TAOs could be obtained，when setting 116.5 ms as the cutoff T2RT value of extraocular muscles. Conclusion：Quantitative measurements of extraocular muscles with T2 mapping could assist in the diagnosis and staging of TAO.

Abstract:The intestinal floras and their metabolites play an important role in cardiovascular disease（CVD）. Changes in the composition of intestinal floras and their metabolites are related to the occurrence and development of atherosclerosis，myocardial infarction，heart failure，and hypertension. The mechanism of the effects of intestinal floras and their metabolites on CVD has been reported. This article will review the role and mechanism of intestinal floras and their metabolites in the development and progression of atherosclerosis，myocardial infarction，heart failure，and hypertension，as well as the potential value in the prevention and treatment of CVD，providing new insights into the prevention and treatment of CVD.

Abstract:Renal cell carcinoma（RCC） is one of most common urinary malignant tumors in China. Surgery is the first selection for the early stage RCC，whereas drug therapy is preferred for the advanced RCC. As VEGF and mTOR inhibitors are approved for the treatment of advanced RCC，the clinical application of targeted drugs improves patients’ prognosis. However，the resistance to VEGF and mTOR targeted therapies is becoming increasingly prominent. In recent decades，immunotherapy，especially programmed cell death-1（PD-1）/programmed cell death-ligand 1（PD-L1） inhibitors and cytotoxic T lymphocyte-associated antigen-4（CTLA-4） inhibitors，has been rapidly developing. These novel checkpoint inhibitors perform well in many clinical trials and improve treatment outcome. This article summarizes the latest data in the development of checkpoint inhibitors for patients with advanced kidney cancer.