Objective To investigate the expression of thymidylate synthase (TS) in bladder urothelial carcinoma(BUC) and its clinical significance, and to evaluate its prognostic value, thus to help predict the prognosis and choose therapy protocal. Methods The expression of TS was assessed by immunohistochemistry in 54 BUC and 15 normal bladder specimens, and all these clinical data were retrospectively analyzed after surgery. Expression of TS,clinicopathologic findings and two prognostic variances (relapse-free survival (RFS) and overall survival (OS)) were determined. The prognostic value of TS was estimated by survival curve and Cox proportional hazards model. Results Immunohistochemistry showed that 25 of 54 BUC cases (46. 30%) had high TS expression. In these cases,there was 29. 41%o (5/17) for G1 ,46. 43% (13/28) for G2,77. 78% (7/9) for G3 ;21.43% (3/14) for Ta, 26. 32% (5/19) for T1, 86. 67% ( 13/15 ) for T2,66.67% (2/3) for T3,66.67% (2/3) for T4. Expression of TS was positively associated with the grade and stage of carcinorma ( Kruskal - Wallis H, P = 0. 0 3 and P ＜ 0. 0 0 1 ). The recurrence and case - fatality of patients with high TS expression was 60. 00% (15/25) and 44. 00% (11/25) ,respectively. The survival analysis and Cox regression analysis showed that expression of TS were independent predictor for recurrence ( RR = 2. 65,95% CI was 0.80～8.81,P＜0.05) anddeath (RR=1.42,95%CIwas0. 36～5.58,P＜0. 05). Conclusions The probability of BUC progress and recurrence increases with the increasing of TS expression. Detection of TS expressing level can contribute to select appropriate treatment and follow-up schema.

Objective To determine,in our experience,the prevalence and presence of risk factors for metabolic syndrome (MS) in heart transplant recipients.Methods We studied 135 patients who underwent heart transplantation in our hospital from September 2000 to December 2011,According to the diagnostic criteria of MS,they were divided into two groups.All variables that could be related to the development of MS during the follow-up period were analyzed.The prevalence and presence of risk factors for MS in our experience were determined.Student t-test,Wilcoxon rank sum test and x2 test were used for univariate statistical analysis and logistic regression for multivariate analysis.Results (1) Of the 135 patients,63 developed MS (46.67％) during a mean follow-up period of 47.3 months.The multivariate analysis identified the follows as predictive factors for the development of MS:age (OR=1.09,95％ CI 1.01-1.22,P＜0.05),body mass index (BMI) (OR=1.65,95％ CI 1.16-1.87,P＜0.05),history of DM (OR =3.27,95％ CI 1.12-34.21,P＜0.05).Conclusion In our population,the prevalence of MS after heart transplant is 46.67％ during a mean follow-up period of 47.3 months.Age,pre-operative overweight especially BMI,and history of DM were significant and independent risk factors for the development of MS during the follow-up period.For these patients,dose of immunosuppressant and diet control are important.

Objective To design and synthesize compounds with protein tyrosine kinase(PTK)inhibitory activity with L029 as the lead compound. Methods L029 derivatives were designed and synthesized from L029 by reduction and/or substitution with the 3-dimethylamino-1-propyl,methyl acetate,methyl propionate in its active H and other sites. PTK activity was measured by enzyme-linked immunosorbent assay(ELISA). The inhibitory rate was calculated to screen out the compounds with PTK inhibitory activity. Re-sults Five target compounds were synthesized and their structures were confirmed by 1H NMR and MS. Three compounds T2,T3 and T5 were screened out with strong PTK inhibitory activity. Conclusion The synthetic routes of the target compounds are simple with mild reaction condition,and 3 compounds show strong inhibitory activity by ELISA. These results can provide reference for the further design and synthesis of this kind of molecules.

Objective To design and synthesize novel 2-indolone derivatives as the c-Met kinase inhibitors. Methods With c-Met kinase inhibitor SU11274 as lead compound,a series of 2-indolone derivatives were designed according to the concept of bioiso-sterism. Then the target compounds(10a-10r)were synthesized from 2-indolone through 5-chlorosulfonation with chlorosulfonic acid, sulfonamidation with intermediate 3,condensation with 6a-6h,7a-7h and 4a-4b,respectively. Their inhibitory activity against c-Met and proliferation of MCF-7 cells were evaluated. Results and Conclusion The designed compounds were successfully prepared and their structures were confirmed by 1H NMR and ESI-MS. Some compounds had certain inhibitory activity against c-Met and prolif-eration of MCF-7 cells. An initial structure-activity relationship analysis of these compounds was performed to provide useful informa-tion for further optimization of their structures.

Objective To study the differential diagnostic efficacy of α-enolase ( ENO1 ) autoantibodies in lung adenocarcinoma , benign pulmonary disease , and normal individuals , and to evaluate the improvement of the diagnostic efficiency of existing markers by establishing a binary logistic regression model.Methods This was a case-control study.Participants were from the public health welfare program led by the National Cancer Center/Chinese Academy of Medical Sciences Peking Union Medical College Cancer Hospital.Serum samples were collected June 2014 to June 2017 including 60 patients with lung adenocarcinoma , 50 patients with benign lung diseases , and 90 healthy controls.Luminex MAGPIX platform was applied to detect serum ENO1 autoantibodies, CEA and Cyfra21-1 proteins.The receiver operating characteristic curve (ROC)analysis and binary logistic regression were used to evaluate the performance and build diagnostic model.Results The median level of serum ENO1 autoantibody in patients with lung adenocarcinoma was 918.5 ( 665.5-2 043.3 ), which was significantly higher than that in the normal individuals (722.5, 585.5-921.8, Z＝-3.113, P＝0.002) and benign lung disease patients (693.0, 501.4-973.3, Z＝-3.395, P＝0.001).And no significant differences between benign disease groups and normal individuals (Z＝-1.155, P＝0.248).ROC was plotted, and the area under the curve (AUC) of ENO1 autoantibodies was 0.664 (95% confidence interval : 0.576-0.752), while the AUCs of existing diagnostic marker CEA and Cyfra21-1 were 0.680 (95% confidence interval : 0.594-0.767) and 0.617 (95% confidence interval: 0.532-0.703).A joint diagnostic model including ENO1 and CEA was built with an AUC of 0.757 (95%confidence interval : 0.675-0.838).The diagnostic efficacy of the model was significantly different from ENO1 autoantibodies (Z＝2.648, P＝0.008).When the specificity was 90%, the sensitivity of ENO1 autoantibodies was 38.3%, while the sensitivity of the combination with CEA was raised to 50%.Conclusion ENO1 autoantibodies could be a marker for the auxiliary diagnosis of lung adenocarcinoma, and can improve the efficacy of the existing diagnostic markers such as CEA .ENO1 has the potential use for the diagnosis and screening.

OBJECTIVETo study differential expression of microRNA (miRNA) in peripheral blood mononuclear cells (PBMNC) from patients with different types of aplastic anemia (AA) and explore the role of miRNA in the pathogenesis of AA.

METHODSmiRNA microarray were used to determine the differential expression profile of miRNA in PBMNC from patients with AA. Real-time quantitative polymerase china reaction (RQ-PCR) was used to verify the differential expression of miRNA. Candidate miRNA were analyzed with bioinformatics tools.

RESULTSCompared with the normal controls, 6 miRNAs were up-regulated and 10 were down-regulated in patients with severe aplastic anemia (SAA), while 24 miRNAs were up-regulated and 12 were down-regulated in patients with chronic non-severe aplastic anemia (CAA). Compared with CAA patients, 4 miRNAs were up-regulated and 11 were down-regulated in SAA patients. Compared with normal controls, 3 miRNAs were up-regulated and 4 were down-regulated in both SAA and CAA patients. As verified by RQ-PCR, expression of miR-155-5p and miR-1260b were increased in both CAA and SAA patients compared with the normal controls (P<0.01). The expression of miR-155-5p and miR-1260b of CAA patients were higher than that of SAA patients (P<0.01). Bioinformatics analysis showed that target genes of miR-155-5p and miR-1260b may be involved in regulation of cell metabolism, gene expression and transcription, TNF signaling pathway, B cell receptor signaling pathway, Fc gamma R-mediated phagocytosis and other signaling process.

CONCLUSIONThere are characteristic differential expression profiles of miRNA in PBMNC from CAA and SAA patients, in which miRNA-155-5p and miRNA-1260b are both up-regulated. The common target gene predicted for miRNA-155-5p and miRNA-1260b is ETS1. miRNA-155-5p and miRNA-1260b may act synergistically to inhibit the expression of ETS1 and promote differentiation of Th17, therefore play an important role in the pathogenesis of AA.

Objective: To investigate the tumor-associated protein molecules carried by plasma exosomes of patients with lung squamous cell carcinoma before treatment and analyze their value as clinical markers. Methods: Exosomes from 2 patients with lung squamous cell carcinoma before treatment and 2 healthy controls were collected by ultracentrifugation. Proteomics was applied to analyze the protein expression profiles of exosomes. Candidate molecules were verified in another 30 exosomes samples from lung squamous cell carcinoma and healthy controls using enzyme-linked immunosorbent assay (ELISA). Results: Electron microscopy and particle-counting assay showed that high-quality exosomes were collected. The number of exosomes distributed from 45 to 135 nm in 2 cases of lung cancer patients were 7.89×10¹¹/ml and 9.71×10¹¹/ml, respectively, significantly higher than 2.76×10¹¹/ml and 1.41×10¹¹/ml in healthy controls. Proteomic analysis showed that proteins of exosomes in lung squamous cell carcinoma patients were very different from those of healthy controls, and some proteins are related to important functions in tumor progression. 14-3-3ζ from exosomes was selected and further verified as a marker, and the area under the receiver operating characteristic curve (ROC) was 0.68. The sensitivity and specificity of 14-3-3 ζ from exosomes were 60.0% and 80.0%, respectively, suggested that it could be used as a diagnostic marker for lung squamous cell carcinoma. Conclusion The exosome counts in plasma and the protein molecules from exosomes, such as 14-3-3ζ, are closely related to the tumorigenesis, which can be used to assist clinical diagnosis of lung squamous cell carcinoma patients.

Objective    To summarize the clinical experience of extracorporeal membrane oxygenation (ECMO) in adult patients with cardiac surgery, analyze the risk factors associated with the mortality and other severe complications and to discuss prevention methods of complications during ECMO treatment. Methods    The clinical data of 26 patients with cardiac surgery, who underwent ECMO because of cardiopulmonary insufficiency ect in Zhongshan Hospital, Fudan University from January 2012 to September 2017, were retrospectively analyzed. There were 19 males and 7 females aged 24–80 (58.0±13.9) years. Results    Twelve (42.3%) patients successfully weaned from ECMO and six (23.1%) were discharged from hospital. Among 26 patients, 24 received VA ECMO (veno-arterial ECMO), including 5 after heart transplantation, 9 after heart valve surgery, and 3 were successfully weaned from ECMO. Seven patients with valvular surgery underwent ECMO within 48 hours due to refractory low cardiac output syndrome (LCOS). Eight patients  underwent major angioplasty, 3 of whom were successfully weaned from ECMO. Four patients underwent coronary artery bypass grafting and other cardiac surgeries. Patients with VA ECMO were treated with femoral vein-femoral artery cannulation except for 2 patients undergoing femoral vein-radial artery cannulation after major angioplasty. Patients with VV ECMO (veno-venous ECMO) underwent femoral vein-jugular vein cannulation. After ECMO support, 10 patients with bleeding occurred, and 5 patients were successfully weaned from ECMO. All patients had transfusion therapy during the assist period, 7 patients had infection after ECMO support, 4 patients suffered severe distal limb ischemia. There was no significant difference in the lactic acid between the survival and the dead patients before and after ECMO support. However, the decline of serum lactic acid in the survivors was faster than that of the dead patients. The trend was the most significant within 6 h after the operation. Conclusion    ECMO is one of the significant treatments for LCOS and refractory hypoxemia after cardiac surgery. The type of cardiac surgery and the timing of catheter placement are key factors for the success of ECMO. The different ways of ECMO intubation, prevention and control of bleeding during ECMO, monitoring and management of internal environment and the strategies of anti-infection are all important for success of ECMO.

Objective    To review and analyze the clinical manifestations of common aortitis in cardiac surgery. Methods    We screened 41 552 patients who were hospitalized in the Department of Cardiac Surgery of Zhongshan Hospital, Fudan University from 2010 to 2020, analyzed the patients' clinical data, and classified according to the type of diseases. Then we summarized all their clinical manifestations. Results    In our center 145 patients were operated for aortitis diseases, including 75 males and 70 females, with the age of 24-76 (45.6±11.3) years. There were 61 patients of Takayasu's arteritis, 51 patients of Behcet's disease, 8 patients of syphilitic aortitis, 8 patients of systemic lupus erythematosus, 2 patients of Kawasaki disease, 4 patients of ankylosing spondylitis, 10 patients of dry syndrome, and 1 patient of scleroderma. Conclusion    Aortitis is not uncommon in cardiac surgery, and awareness of the disease should be enhanced. So that we can distinguish various types of aortitis and to make proper management to improve patients' prognosis.