Structural heart diseases refer to anatomic heart or great vessels abnormalities by congential or acquired factors, including congenital heart disease, acquired heart valve disease, cardiomyopathy. In recent years, interventional therapy in structural heart diseases has gradually matured and been widely applied in clinical practice. Due to the fragility of heart valves and valve related organizations, or the congenital dysplasia of valves, the complex interventional therapeutic procedures can cause valve-related complications. In this paper, the causes, prevention and treatment of valve-related complications induced by interventional therapy in structural heart diseases are introduced.

Objective Through observation of the expression and activity of extracellular regulated protein kinase 5 (ERK5) and its relationship with the learning and memory ability in rats with chronic fluorosis,to further study the pathogenesis of chronic fluorosis in nervous system.Methods Thirty SD rats were divided into 3 groups according to body weight by means of a random number table (10 rats in each group,half male and half female).The rats in control group were fed with free drinking tap water containing less than 0.5 mg/L fluoride (NaF);the rats in low fluoride group with 10.0 mg/L fluoride;the rat in high dose fluoride group with 50.0 mg/L fluoride.After 6months of experiment,rat brain tissue was took,mRNA expression level of ERK5 was detected by real-time fluorescence quantitative PCR (real-time PCR),protein expression level and activity of ERK5 were detected by Western blotting;the learning and memory ability of rats with chronic fluorosis were detected by Morris water maze test.Results The rat in groups exposed to fluoride exhibited different degrees of dental fluorosis and the fluoride content in urine of rats increased gradually with increase of fluoride doses (F =164.10,P ＜ 0.05).The protein levels of phosphor-ERK5 in the control group,low fluoride group and high fluoride group were 0.13 ± 0.03,0.29 ± 0.10and 0.43 ±0.17,respectively,the difference was statistically significant (F=11.96,P＜ 0.05),and low fluoride group and high fluoride group were higher than control group (all P ＜ 0.05).The total protein levels of ERK5 in control group,low fluoride group and high fluoride group were 0.32 ± 0.11,0.37 ± 0.13 and 0.49 ± 0.16,respectively,the difference was statistically significant (F =3.45,P ＜ 0.05),and high fluoride group was higher than control group (P ＜ 0.05).The expression of ERK5 mRNA in rat brains between groups was not significantly different (F =0.81,P ＞ 0.05).The second,third,and forth days of directional navigation experiment,the time of escape latency and the number of crossing the platform between groups were statistically significant (H =28.20,29.90,26.47,27.23,35.34,27.62,all P ＜ 0.01);the fifth day of space exploration experiment,the difference of the time of the first crossing platform and the number of crossing the platform between groups were statistically significant (H =31.41,30.80,all P ＜ 0.01);the protein level of phosphor-ERK5 in brain tissue of rats was negatively correlated with the number of the first crossing platform (r =-0.470,P ＜ 0.01),while positively related to escape latencies at the fifth day of the test (r =0.591,P ＜ 0.01).Conclusion The changes of ERK5 signaling pathway in rat brain tissue caused by chronic fluorosis are found,which are related to the decrease of leaming and memory ability of animals with chronic fluorosis.

Objective To review and summarize the experiences of modified extracardiac conduit Fontan operation for heterotaxia syndrome with complex congenital heart disease. Methods There were 11 patients with cynosis complex congenital heart disease, 9 were aspleenia syndrome (right atrium isomerism, including 6 single ventricle with common atrioventricular valve, 2 double outlet right ventricle with atrioventricular discordance, and 1 corrected transposition of the great arteries), and 2 were polyspleenia (left atrium isomerism, double outlet right ventricle with common atrioventricular valve). The mean age was (6.3?3.7)year-old, the mean body weight was (21.0?5.5)kg. 3 patients underwent one-stage modified extracardiac conduit Fontan procedure, 8 patients after bi-directional Glenn operation underwent two-stage procedure. Results During early postoperative period, two patients had low cardiac output syndrome, 1 renal dysfunction; and 1 supraventricle tachycardiac. The time of chest drainage (120*!ml/d) was more than 10 days in 2 patients. 2D-echo showed that superior vena cava blood flow rate was 0.6 to 0.8 m/s, inferior vena cava flow rate was 0.3 to 0.4 m/s. Oxygen saturation were from 0.92 to 0.95 in room air in 9 patients, 2 patients were under 0.86. The exercise capacity was significantly improved. All patients were survived and no early death. At follow-up ranging from 6 months to 2 years, supra vena cava blood flow rate was 0.8*!m/s, inferior vena cava flow rate is 0.4 to 0.7*!m/s. There was no thrombus formation in the conduit. The diameter of fenestration was 0.34*!cm and blood flow from right to left. No pulmonary vein drainage obstruction. Heart function was normal. No atrial arrhythemia were detected. The oxygen saturation in the room air was more than 0.90. No chronic effusion and protein-losing enteropathy, no mid-term death. Conclusion Modified extracardiac conduit Fontan operation is suited for heterotaxia syndrome with complex congenital heart disease. The incidence of arrhythemia is low.

Objective To analyze the immunogenomic characteristics of antibody repertoire in re-sponse to influenza vaccine in order to provide a theoretical basis for further development of antibody. Meth-ods Based on a time-series immunoglobulin heavy chain ( IGH) repertoire sequencing dataset, we analyzed the immunogenomic characteristics of antibody repertoire in response to trivalent influenza vaccine ( TIV ) from three aspects which included the features in complementarity-determining region 3 ( CDR3 ) , antibody mutation and VDJ usage. Results The frequency of antibody mutation increased significantly upon vaccina-tion. Analysis of the CDR3 region indicated that polar and aromatic amino acids had a higher preference. The length of CDR3 region in naive B cells followed a normal distribution, while specific CDR3 sequences with 15 to 18 amino acids in length occupied a dominant position after vaccination. In addition, the VDJ us-age altered obviously and IGHV3-7-derived antibody had a significant response to the vaccine. Response in-tensity reached the peak on day 7 and gradually weakened over time. Conclusion Antibody repertoire evolves dynamically to express specific antibody upon vaccination and the characteristics of immune responses at sequence level could be used to evaluate their effectiveness.

Objective To evaluate accurately the cardiac output, an early post-operative indicator for the cardiac function, after cardiac surgery in the neonates with congenital heart diseases and assess the risk factors for surgery, with an aim at exploring the early strategy for decressing the mortality. Methods From January 2007 to November 2007, forty-seven consec-utive neonates with complex congenital heart diseases underwent surgical correction at Shanghai Children's medical center.There were 38 boys and 9 girls with age from 3 days to 29 days [mean age (21.98 +8.15) days] and weight from 2.6 kg to 4.2 kg [ mean (3.49±0.51 ) kg]. 15 patients had delayed sternal clousure. The operations were performed with hypothermia, deep hypothermia low flow, or deep hypothermia circulatory arrest techniques. Cardiac index (CI) was derived from pulse contour analysis and calculated with the PiCCO plus system. Meanwhile, serum cardiac troponin I ( cTnl), mixed venous oxygen saturation ( SvO_2 ) and cardiopulmonary bypass (CPB) time were measured. Finally, the risk factors for surgical treatment in survivors and that associated with an increased mortality were analyzed. The association between post-operative cardiac output and the death after surgery was examined. Results Four neonates died after surgery, with a surgical mortality of 8.5%. CIvalue in the neonates [ (2.0±0.3 ) liters per minute per square meter of body surface was less than normal 2.5±0. 3. CI was associated inversely with CPB time but had a positive correlation with SvO_2. No significant difference association between CI and cTnI was observed. The value of cTnl was associated with the type of surgical procedures. Cases for which DHCA and low flow cerebral pefusion technique were used were free from neurological complications, ischemia in the lower extremities and oli-guria. The duration of cardiopulmonary bypass, urgent state of the operation and the abnormal coronary artery were associated with high mortality in the neonates after cardiac surgery. Conclusion The cardiac output of the neonates in whom cardiac pro-cedures were performed is adequate for the the oxygen supply required by the whole body though it is slightly lower than nomad after cardiac surgery. Higher mortality in the neonates during early postoperative period may be due to the complexity of the primary diseases, prolonged cardiopulmonary bypass time, residual abnormalities and severe acidosis before operation. Various techniques for CPB and that for the myocardial protection are safe and can provide an appropriate operative field.

Objective To investigate the influence of chronic fluorosis on protein kinase Cβ (PKCβ)/p66shc signal pathway in the brain of rats,and reveal the molecular mechanism of brain damage.Methods According to body weight by the random number table method thirty SD rats were divided into three groups of 10 each (half females and half males),the normal control group [less than 0.5 mg/L of fluorine (prepared with NaF) in drinking water],low fluoride exposure group (10.0 mg/L fluorine),and high fluoride exposure group (50.0 mg/L fluoride).The experiment period was 6 months.The protein level of PKCβ,p66shc,phospho-p66shc and preserved ammonia acyl isomerase (Pin1) in rat brain was detected by Western blotting.The level of neuron nuclear antigen (NeuN),p66shc and phospho-p66sh in brain of rats was detected by immunohistochemistry.Results By Western blotting,the levels of PKCβ,Pin1 and phospho-p66shc protein in brain tissue in high fluoride exposure group [(193.00 ± 57.53)％,(228.21 ± 71.14)％,(201.54 ±:50.86)％] were higher than those of the normal control groups [(100.00 ± 21.24)％,(100.00 ± 40.55)％,(100.00 ± 13.35)％,all P ＜ 0.05].By immunohistochemistry,the numbers of NeuN staining in brain tissue of the rats in both high and low fluoride exposure groups [(49.50 ± 12.57)％,(65.66 ±14.58)％] were lower than that of the control group [(100.00 ± 18.32)％,all P ＜ 0.01].The level of phospho-p66shc protein in brain tissue in high fluoride exposure group [(242.66 ± 93.01)％] was higher than those of the low fluoride exposure and the normal control groups [(152.53 ± 60.65)％,(100.00 ± 25.63)％,all P ＜ 0.01].Conclusion Chronic fluorosis has increased the expressions of PKCβ,Pin1 and phospho-p66shc at protein level in brain of rats,which may be related to the molecular mechanism of brain damage resulted from chronic fluorosis.

Objective The goal of this study is to understand the function of FKBP51 in resistant to high fat diet-induced obesity using FKBP51 knockout ( KO) mice and in vitro adipocyte differentiation.Methods Four-week old male FKBP51 KO and wild type ( WT) mice were fed separately with regular or high fat diet for 6 weeks.The body weight and food consumption were recorded weekly, the energy expenditure differences ( O2 consumption, CO2 production, respiratory exchange ratio, and heat production) of each group were monitored using the MM-100 metabolism cages system for 24 hours, then the liver from the above animals were stained with the Oil red-O to detect the lipid accumulation and the expression of metabolic genes.In addition, induction of adipocyte differentiation of immortalized MEF cells from WT and FKBP51 KO mice were used to observe the effect of FKBP51 gene on lipogenesis.Results Compared to WT mice, FKBP51 KO mice has less weight increment, and less lipid accumulation in the liver, but with no difference on food consumption during high-fat diet fed.Moreover, FKBP51 KO mice exhibited more O2 consumption, CO2 production and heated production under both RD and HF diet conditions.The PEPCK, G6Pase and UCP-1 genes up-regulation.In addition, lipid content was reduced in FKBP51 gene deficient MEF cells after adipocyte differentiation.Conclusions The FKBP51 gene plays an important role in high fat diet-induced obesity through the energy metabolism enhancement and lipogenesis inhibition.

Objective To evaluate the usefulness of anti -HCV signal-to-cutoff (S/CO)ratio, AST, ALT and the combined examination of anti-HCV S/CO, AST, ALT for predicting HCV RNA results by a model of logistic regression and receiver -operating characteristic (ROC) curve.Methods Five hundred and eighty -eight anti-HCV positive samples were tested by ELISA , followed by RT-PCR to detect HCV-RNA and enzyme rate method to detect AST, ALT.Patients were divided into viremia and non -viremia groups according to HCV-RNA results.Logistic regression and ROC curve analysis was performed to evaluate the diagnostic accuracy of each index for a diagnosis of viremia.Results The serum anti-HCV S/CO ratio, AST, ALT of HCV-RNA positive group were higher than HCV-RNA negative group, showing significant statistical difference ( P <0.05).Anti-HCV S/CO, AST and ALT has a closely posi-tive correlation with HCV-RNA ( P <0.05), anti-HCV S /CO >AST >ALT.The Area Under Curve(AUC) of the combined examina-tion of anti-HCV S/CO ratio, AST and ALT was 0.949(95% confidence interval,0.932 to 0.966), higher than the AUC of anti-HCV S/CO ratio, AST and ALT single index examinations , which was 0.894(95 % confidence interval, 0.862 to 0.926), 0.823(95%confidence interval, 0.789 to 0.856) and 0.788(95% confidence interval, 0.750 to0.826 ) respectively.C onclusions The diag-nostic relevance of the three biochemical markers for predicting the presence of viremia was anti -HCV S/CO ratio >AST >ALT.The combined examination of anti-HCV S /CO ratio, AST and ALT in predicting hepatitis C viremia is superior to any single index examina -tion and it can increase the detecting ability of HCV -RNA greatly.

Surgery remains the primary treatment for patients with localized gastrointestinal stromal tumor (GIST), however, even after complete resection of the tumor, there is still a part of patients with tumor recurrence and metastasis. Imatinib, as adjuvant therapy in GIST patients with intermediate and high risk of recurrence, can significantly improve the disease-free survival, but whether it can prolong the overall survival is still unknown. It has reached a consensus that the intermediate and high risk patients should receive adjuvant therapy, but the duration for adjuvant therapy is still under investigation, especially for high-risk patients. Adjuvant therapy is recommended for at least 3 years, while in the end of adjuvant therapy, some patients still develop recurrence and metastasis. In 2017, results from PERSIST-5 study reported by the ASCO conference indicated that 5-year adjuvant therapy may further prolong disease-free survival of intermediate and high risk patients. In addition, adjuvant therapy is still not individualized based on the combination with different genotypes, and present adjuvant therapy is recommended for GIST patients with positive CD117 and intermediate-high risk of recurrence. It remains controversial whether different genotypes are associated with alternative adjuvant treatment options. Results of more researches are expected to provide better guidance for clinical treatment in the future.

Objective To evaluate the clinical effect for transcatheter closure of intracristal ventricular septal defects (IVSD) using duct occluder.Methods Between Jun.2012 and Sep.2013,implantaion of duct occluder was conducted in 27 IVSD pmients,which was compmed with acentric ventricular septal occluder attempted in 53 IVSD patients.The transthoracic echocardiography,electrocardiography,and clinical examination were observed at 24 hours,and after 1,3,6 and 12 months follows-up.Results Implantation of duct occluders were achieved in 26 (96.23 ％) patients and implantation of acentric ventricular septal occluder in 42 (79.25％) patients.The mean follow-up time was 6.78 months (1-17 months).The procedure time,fluoroscopic time and residual shunt were not statistically different between the 2 groups (all p ＞ 0.05).The size of VSD (t =-3.124,P =0.003) and occluder diameter (t =-4.285,P ＜0.001)were smaller and the procedure success rate was higher in the duct occluder group (x2 =9.099,P =0.011).Left ventricular end diastolic dimension,left atrial diameter,left ventricular end diastolic dimension,right ventricular end diastolic dimension and pulmonary artery diameter were decreased significantly (F =57.62,5.002,4.754,2.782,P =0.000,0.033,0.001,0.030) after surgical procedure compared with those before procedure,except for the right atrial diameter and left ventricular ejection fraction.No new serious aortic regurgitation or increased mitral regurgitation,tricuspid regurgitation was shown after procedure in 2 groups.Complete left bundle branch block occurred in 2 patients respectively,pericardial effusion and thromboembolism of right femoral artery occurred in 1 patient in the acentric ventricular septal occluder group.Conclusions The duct occluder for IVSD closure has presented a good result,without serious complications,which provides a new method for IVSD closure.Further studies are necessary to determine the long-term results in a larger population of patients.