Objective To investigate the regulatory mechanism of transforming growth factor-β1 (TGF-β1) in different types of mitral valvular disease (MVD) with atrial fibrillation (AF). Methods From August 2011 to August 2012, patients with moderate to severe MVD accompanied by AF who required mitral valve replacement at the Department of Cardiovascular Surgery, West China Hospital, Sichuan University, were included. Based on echocardiographic results, patients were divided into two groups: a mitral regurgitation (MR) with AF (MR-AF) group and a mitral stenosis (MS) with AF (MS-AF) group. Left atrial tissue samples were collected during surgery. Techniques such as enzyme-linked immunosorbent assay, real-time fluorescence quantitative polymerase chain reaction, immunohistochemistry, and Western blotting were used to detect key molecules in the TGF-β1/JNK pathway. Results Sixteen patients were enrolled. There were 8 patients in the MR-AF group, including 5 males and 3 females, with an average age of (41.38±11.19) years; and 8 patients in the MS-AF group, including 6 males and 2 females, with an average age of (43.12±5.30) years. The left atrial volume load was higher in MR-AF patients, while the left atrial pressure load was higher in MS-AF patients. In MS-AF patients, the relative expression levels of MAPK9, JUN, CASP3, BAX, and BCL2 mRNA in left atrial tissues were significantly upregulated. The serum TGF-β1 protein level and the relative expression levels of p-JNK, p-c-Jun, and Caspase-3 proteins in the left atrial tissues of the MR-AF group were higher. Myocardial cell damage was more severe in the MS-AF group, and the protein expression level of Bcl-2 was higher. Conclusion Different MVD have distinct hemodynamic characteristics. The myocardium of the left atrium in MR-AF patients is more prone to apoptosis, possibly through the activation of the TGF-β1/JNK signaling pathway.

Objective:To investigate the differential gene expression profiles of alpha-fetoprotein (AFP) high- and low-expressing hepatocellular carcinoma (HCC), and to provide a theoretical basis for the molecular mechanism and prognosis analysis of HCC.Methods:The transcriptome data and related clinical information from 368 HCC cases were obtained from the Cancer Gene Atlas (TCGA) public database. The samples were divided into AFP high expression (AFP high) group and low expression (AFP low) group according to the quartile of AFP mRNA expression, with 92 cases in each group. The differential gene analysis was carried out using the DEseq2 package in the R software. The functional and KEGG pathway enrichment analysis of the differential genes was performed using ClusterProfiler package. The protein-protein interaction network was constructed to screen hub genes using the String database and Cytoscape software. The single-sample GSEA analysis was performed to enrich and score signature gene sets using the GSVA package. And then RNAseq data and real-time quantitative polymerase chain reaction (RT-qPCR) were used for independent dataset validation and tissue validation. Results:The clinical analysis showed that high expression of AFP was significantly associated with poor pathological differentiation and ethnicity ( P<0.05 for both). A total of 1 382 differential genes were obtained by bioinformatics analysis, of which 931 genes were up-regulated and 451 genes were down-regulated in AFP high group. GO enrichment analysis showed that the highly expressed genes were mainly correlated with the processes of appendage development, limb development, and skeletal system development, while lowly expressed genes were related to metabolic-related processes such as xenobiotic metabolism, steroid metabolism, and cellular response to xenobiotic stimuli. KEGG pathway enrichment analysis revealed that highly expressed genes were mainly involved in primary immunodeficiency, neuroactive ligand-receptor interaction, and cytokine-cytokine receptor interaction, while lowly expressed genes were mainly involved in retinol metabolism, chemical carcinogenesis, steroid hormone biosynthesis and other pathways. A prognostic related gene set that was consisted of AURKB, TTK, CENPA, UBE2C, HJURP, and KIF15 was identified. And the high expression of this gene set was related to the shorter recurrence-free survival and overall survival time in HCC patients, and its enrichment score was positively correlated with AFP expression ( r=0.475, P<0.001). The validation results of RNAseq data were basically consistent with the TCGA data. The RT-qPCR results showed that AURKB, KIF15, and UBE2C were significantly overexpressed in HCC tissues with high AFP expression. Although the expression of AURKB, TTK, KIF15, and UBE2C was not related to recurrence-free survival and overall survival of HCC patients, there was a tendency that the patients with high AFP levels showed relatively shorter recurrence-free survival time and overall survival time. Conclusions:There is a large difference in gene expression profiles between AFP high and AFP low HCC. The prognostic signature may cooperate with AFP to promote the initiation and development of HCC. It also may explain the tumorigenesis in HCC with different AFP levels, and provide new clues for the prognosis of HCC.

Objective:To investigate the differential gene expression profiles of alpha-fetoprotein (AFP) high- and low-expressing hepatocellular carcinoma (HCC), and to provide a theoretical basis for the molecular mechanism and prognosis analysis of HCC.Methods:The transcriptome data and related clinical information from 368 HCC cases were obtained from the Cancer Gene Atlas (TCGA) public database. The samples were divided into AFP high expression (AFP high) group and low expression (AFP low) group according to the quartile of AFP mRNA expression, with 92 cases in each group. The differential gene analysis was carried out using the DEseq2 package in the R software. The functional and KEGG pathway enrichment analysis of the differential genes was performed using ClusterProfiler package. The protein-protein interaction network was constructed to screen hub genes using the String database and Cytoscape software. The single-sample GSEA analysis was performed to enrich and score signature gene sets using the GSVA package. And then RNAseq data and real-time quantitative polymerase chain reaction (RT-qPCR) were used for independent dataset validation and tissue validation. Results:The clinical analysis showed that high expression of AFP was significantly associated with poor pathological differentiation and ethnicity ( P<0.05 for both). A total of 1 382 differential genes were obtained by bioinformatics analysis, of which 931 genes were up-regulated and 451 genes were down-regulated in AFP high group. GO enrichment analysis showed that the highly expressed genes were mainly correlated with the processes of appendage development, limb development, and skeletal system development, while lowly expressed genes were related to metabolic-related processes such as xenobiotic metabolism, steroid metabolism, and cellular response to xenobiotic stimuli. KEGG pathway enrichment analysis revealed that highly expressed genes were mainly involved in primary immunodeficiency, neuroactive ligand-receptor interaction, and cytokine-cytokine receptor interaction, while lowly expressed genes were mainly involved in retinol metabolism, chemical carcinogenesis, steroid hormone biosynthesis and other pathways. A prognostic related gene set that was consisted of AURKB, TTK, CENPA, UBE2C, HJURP, and KIF15 was identified. And the high expression of this gene set was related to the shorter recurrence-free survival and overall survival time in HCC patients, and its enrichment score was positively correlated with AFP expression ( r=0.475, P<0.001). The validation results of RNAseq data were basically consistent with the TCGA data. The RT-qPCR results showed that AURKB, KIF15, and UBE2C were significantly overexpressed in HCC tissues with high AFP expression. Although the expression of AURKB, TTK, KIF15, and UBE2C was not related to recurrence-free survival and overall survival of HCC patients, there was a tendency that the patients with high AFP levels showed relatively shorter recurrence-free survival time and overall survival time. Conclusions:There is a large difference in gene expression profiles between AFP high and AFP low HCC. The prognostic signature may cooperate with AFP to promote the initiation and development of HCC. It also may explain the tumorigenesis in HCC with different AFP levels, and provide new clues for the prognosis of HCC.

Objective    To evaluate the quality of warfarin anticoagulant therapy in patients with stable stage after mechanical valve replacement surgery, to observe the effect of compound salvia miltiorrhiza tablet on the anticoagulant effect of warfarin in patients after mechanical valve replacement, and to understand the impact of genetic polymorphisms of VKORC1, CYP2C9 and CYP4F2 on warfarin resistance in patients with mechanical valve replacement in the stable period. Methods    From July 2011 to February 2014, 1 831 patients who had ≥ 6 months after mechanical valve  replacement surgery were enrolled at the outpatient follow-up. The basic clinical data were recorded. Anticoagulant therapy uses a target international normalized ratio（INR, 1.60–2.20) and a weekly warfarin dose adjustment strategy. Forty-six patients who needed compound salvia miltiorrhiza tablet were screened and the INR values. Before and after taking tablets were recorded and compared. The patients were divided into three groups according to the percentile of warfarin dosage including a warfarin sensitive patients group, a control patients group, and a warfarin resistance patients group. And 101 of them were selected. TIANGEN blood DNA Kit blood genomic DNA extraction kit was used to extract samples and polymerase chain restriction fragment length polymorphism (PCR-RELP) was used to determine the genotypes of patients. The detected gene loci included CYP4F2: rs2108622C>T locus; VKORC1:1639G>A locus; VKORC1:1173C>T locus; CYP2C9*2: rs1799853C>T locus; CYP2C9*3:1061A>C locus. Results    The time in therapeutic range (TTR) and fraction of time in therapeutic range (FTTR) in the target INR range of the patients included in the study period was 27.2% and 49.4%, respectively, and the TTR and FTTR in the acceptable INR range was 34.25% and 63.36%, respectively. Before and after the addition of compound salvia miltiorrhiza tablets, the INR value was 1.55±0.03 and 1.69±0.30, respectively, and the difference was statistically different (P<0.05). A total of 101 patients with genetic testing, in which the C/T composition of the VKORC1: 1173C>T locus increased in the warfarin sensitivity, contrast and warfarin resistance patients, while the ratio of allelic loci of C/T in CYP2C9*3: 1061A>C loci decreased in turn. There was no difference in the CYP4F2 gene, VKORC1639 gene, and CYP2C9*2 locus. The IWPC model predicts that warfarin dose is only consistent with the actual warfarin dose in warfarin sensitive patients. Conclusion    Relatively low TTR and FTTR are acceptable in patients with stable stage after mechanical valve replacement. It is beneficial to the patients with compound salvia miltiorrhiza tablets in terms of some appropriate patients. VKORC1: 1173C>T site and CYP2C9*3: 1061A>C site mutation is the main pharmacological gene factor of warfarin dose sensitivity and warfarin resistance in stable period after mechanical valve replacement. The IWPC dose prediction model is only consistent with the actual dose of warfarin sensitive patients.

The incidence of postoperative excessive bleeding and reexploration is relatively high, and it will bring a series of serious complications, such as an additional surgery, a longer intensive care unit stay, longer time on mechanical ventilation, an increase need of allogeneic blood product transfusions and increased mortality. However, the understanding of postoperative excessive bleeding and reexploration in China is significantly different from the international level, and the understanding of postoperative excessive bleeding and reexploration after cardiac surgery in clinical work is still not enough. This review will focus on some problems, such as related factors analysis of postoperative excessive bleeding, hemostatic process optimization and the serious complications of reexploration after cardiac surgery.

The patients with mechanical prosthetic valve replacement need anticoagulant therapy for all their life. The incidence of thromboembolism and anticoagulation-related bleeding events still account for major postoperative complications after mechanical heart valve replacement. Most of the complications happen in the first half year after operation. Therefore, early anticoagulation therapy is very important. Of course, so far most guidelines focus stating their opinions on long-term anticoagulant therapy. However, there is no consensus about anticoagulant therapy in the early period of postoperation. In this review, we summarize early anticoagulant therapy of the patients with mechanical heart valve replacement through consulting domestic and abroad relevant research in recent years and give an overview of the present situations of early anticoagulant therapy.

The main purpose of this study is to observe and analyze the characteristics and the clinical significance of long-term echocardiogram data in patients after mechanical aortic valve replacement operation. Fifty-five cases were recruited over 5 years after mechanical aortic valve replacement operation, with complete echocardiogram examination profiles. The 55 subjects were divided into predominate aortic stenosis group and predominate aortic regurgitation group, based on preoperative examinations. And another way of division was also carried out that according to the effective orifice area index (EOAI), the subjects were divided into three groups, i. e. , severe prosthesis-patient mismatch (PPM) group, moderate PPM group, and non PPM group. Characteristics of long-term echocardiogram data of the subjects were analyzed. Patients with aortic stenosis showed significantly decreased thickness of intraventricular septum and left ventricular posterior wall about half a year after operation (P < 0.05). Half a year after operation, patients with aortic regurgitation showed decreased left ventricular internal dimension diastole and left ventricular internal dimension systole, and increased ejection fraction (P < 0.05). Differences in mean aortic valve pressure gradient, forward blood flow across the aortic valves, and ejection fraction were not significant among those with severe PPM, moderate PPM, and non PPM groups (P > 0.05). Number of cases of ascending aorta dimension increased as time goes on and pathogenesis of other valve diseases. A conclusion could be drawn that the heart function of patients with aortic valve disease could be improved after mechanical aortic valve replacement operation, but pathologies in other valves and ascending aorta might be increased, and therefore periodical postoperative echocardiogram evaluation with long-term pharmaceutical therapy could be necessary.
Aortic Valve Stenosis ; surgery ; Echocardiography ; Heart Valve Prosthesis ; Heart Valve Prosthesis Implantation ; Heart Ventricles ; anatomy & histology ; Humans ; Postoperative Period ; Systole ; Treatment Outcome

Objective To verify the feasibility and accuracy in the measurement of tricuspid valve annulus diameter(TVD) in the right ventricular outflow tract view.Methods Seventy five patients under the valve replacement surgery for the left heart valve lesions were divided into mild,moderate and severe group according to the severity of the regurgitation.The TVD was get on the apical four-chamber heart viewpreoperatively by transthoracic echocardiography(TTE),noted as TTE-TVD,meanwhile it was also get by the transesophageal echocardiography on the four-chamber view (TEE-TVD),right ventricular inflow (RVIT-TVD) and outflow tract view(RVOT-TVD).The changes of tricuspid regurgitation severtity was observed preoperatively.And the morphology of tricuspid annulus were observed using both real-time three dimensional transesophageal echocardiography (RT-3D TEE) and the quantitative software.Results Comparison in the groups:no statistically significant difference (P ＞0.05) was found between TTE-TVD,TEE-TVD and RVIT-TVD;while the RVOT-TVD was significant greater than that in the same group from other views (P ＜ 0.05).Comparison between the groups:no significant difference was found between mild and moderate regurgitation group on the same view.There was a significant difference of the TVD between the severe regurgitation group and the former two groups on each view(P ＜0.05).The severity of tricuspid regurgitation in intraoperative anesthesia was reduced.The saddle tricuspid ring evolved into the narrow planar structure on the RT-3D TEE.For the expansion of the annulus,it departure from the tricuspid septal leaflet.Conclusions TVD measured on the right ventricular outflow tract view reflect the maximum expansion of the tricuspid valve annulus diameter,and can effectively guide the decision-making choices of the surgeon.

Objective To evaluate the method of low-intensity anticoagulation therapy in the pregnant women who had received mechanical heart valve replacemant, and the effects of warfarin on the pregnant women and their fetus. Methods This retrospective study involved 56 pregnant women( 61 pregnancies)who had received mechanical heart valve replacement.Their pregnant status, delivery, and anticoagulation therapy were observed and followed-up between May 1986 and November 2009 at West China Hospital of Sichuan University. Results All patients took oral anticoagulant (warfarin) throughout pregnancy. The dose of domestic warfarin was ( 3.02 ± 0.85 ) mg/d ( in 42 cases), and the dose of imported warfarin was (2.84 ± 0.57 )mg/d (in 14 cases). The mean INR value of 401 samples from patients was 1.67 ±0.58. No thromboembolism or major hemorrhagic complications occurred. Minor bleeding occurred in 11 pregnancies. Forty-seven patients had term delivery, 7 had premature birth, 6 had spontaneous abortion, and 1 had intrauterine fetal death. Six newborns were born with low birth weight (2.3 ± 0. 5 ) kg, and no abnormal fetus was observed. Conclusion The low-intensity anticoagulation therapy with warfarin (at a dose of less than 5 mg/d) and a INR target of 1.5 to 2.0 was safe and convenient for the pregnant women,who had received mechanical heart valve replacement. The abnormalities rate of fetus was low.

Objective　To explore the effect of amrinone and aprotinin on whole-body inflammatory response in the patients with prosthetic valve replacement during perioperative period. Methods　24 patients undergoing prosthetic valve replacment were randomized to control group (group A, n=8) , aprotinin group (group B, n=8) and amrinone combined with aprotinin group (group C, n=8). In the aprotinin group, 3×106 of aprotinin was added to the priming solution of the extracorporeal circulation (ECC). In the amrinone combined with aprotinin group 3×106 of aprotinin was added to the priming solution of the ECC and amrinone began with a bolus of 1mg/kg followed by a maintenance infusion of 8μg/(kg*min). The control group received an equivalent prime volume without aprotinin. Venous blood samples were drawn before the operation, at the end of ECC, 1 hour after the end of ECC, and one day after the operation respectively. Enzyme-linked immunosorbent assay techniques were used to measure each of the cytokines. Results　Before ECC, there were no differences of the levels of IL-6 and IL-8 among groups (P>0.05). After ECC, the levels of IL-6 and IL-8 increased significantly in all groups (P<0.05). The levels on day one after the operation were still higher than those before the operation in all groups (except the level of IL-8 in group C), but no statistical significance was observed. (P>0.05). At 1 hour after the end of ECC, the level of IL-6 in group B was lower than that in group A, and the level of IL-6 in group C was lower than that in group B, but there was no statistically significant difference (P>0.05）；At the end of ECC, the level of IL-8 in group B was lower than that in group A and the level of IL-8 in group C was lower than that in group B, but no significant difference was noted (P>0.05). It was also observed that the level of IL-8 was lower in group C than group A or B at 1 hour after the end of ECC. Conclusion　Although amrinone and aprotinin have antiinflammatory activity, but pump prime only aprotinin or aprotinin combined with amrinone may fail in preventing proinflammatory cytokine release (IL-6, IL-8) completely in patients with prosthetic valve replacement during ECC perioperative period.