Evaluation of left ventricular blood flow kinetic energy in patients with hypertension by four-dimensional flow cardiovascular magnetic resonance imaging: a preliminary study.

OBJECTIVES: To evaluate the intra-cavity left ventricular (LV) blood flow kinetic energy (KE) parameters using four-dimensional (4D) flow cardiovascular magnetic resonance (CMR) in patients with hypertension (HTN). METHODS: Forty-two HTN patients and twenty age-/gender-matched healthy controls who underwent CMR including cines, pre-/post-T1 mapping, and whole-heart 4D flow imaging were retrospectively evaluated. HTN patients were further divided into two subgroups: with preserved ejection fraction (HTN-pEF) and with reduced ejection fraction (HTN-rEF). KE parameters were indexed to LV end-diastolic volume (EDV) to obtain averaged LV, minimal, systolic, diastolic, peak E-wave, peak A-wave, E-wave, and A-wave KEiEDV, as well as the proportion of in-plane LV KE (%), the time difference (TD). These parameters were compared between the HTN group and healthy controls, also between two subgroups. The correlation of LV blood flow KE parameters with LV function and extracellular volume fraction (ECV) were analyzed in the HTN group using multivariate regression analysis. RESULTS: Peak E-wave KEiEDV in the HTN group was significantly lower (p = 0.01), while in-plane KE and TD were significantly higher (all p < 0.01) than those in healthy controls. Compared to the HTN-pEF subgroup, the proportion of in-plane KE and TD was significantly increased in the HTN-rEF subgroup (all p < 0.01). Only the proportion of in-plane KE demonstrated an independent correlation with ECV (ß* = 0.59, p < 0.01). CONCLUSIONS: The decreased peak E-wave KEiEDV and the increased proportion of in-plane KE, TD reflected the alterations of LV blood flow in HTN patients, and the proportion of in-plane KE was independently associated with ECV. KEY POINTS: • 4D flow CMR demonstrated that the peak E-wave KEiEDV was decreased, while the in-plane KE and time difference (TD) were increased in hypertensive (HTN) patients. • The proportion of in-plane KE and TD was further increased in HTN patients with reduced ejection fraction than in HTN patients with preserved ejection fraction, and the proportion of in-plane KE was independently associated with extracellular volume fraction in HTN patients. • 4D flow CMR intra-cavity blood flow KE parameters might reveal the LV hemodynamic status in preclinical HTN patients.

Prognostic value of plasma sAXL in patients with heart failure: insights from the DRAGON-HF trial.

BACKGROUND: Little is known about the predictive value of soluble AXL (sAXL) in heart failure (HF). This study aimed to describe the prognostic value of plasma sAXL in patients with symptomatic HF. METHODS: This is a multicentre observational prospective cohort study (Registration No. NCT03727828). Plasma sAXL were measured on admission. The primary endpoint is a composite of cardiovascular mortality and HF rehospitalization. Associations between plasma sAXL levels and clinical endpoints are described using Cox regression models and Kaplan-Meier methods. RESULTS: A total of 1030 symptomatic HF patients were enrolled in the study; the mean age (65% men) was 71 ± 12 years, with a median follow-up of 32 months (IQR: 26-41 months). The mean baseline sAXL levels were 20.03 ± 6.74 ng/mL. Plasma sAXL positively associated with NYHA classification and negatively associated with left ventricular ejection fraction (both P < 0.001). Cox regression showed that 1-SD increment of sAXL was associated with primary endpoint [HR (CI): 1.128 (1.024-1.242)], cardiovascular mortality [1.112 (1.032-1.198)], all-cause mortality [1.142 (1.057-1.234)], and HF rehospitalization [1.122 (1.030-1.224)] after adjustment for potential confounders including NT-proBNP. Kaplan-Meier curves revealed that patients with the highest sAXL levels were at the highest risk of primary endpoint events, cardiovascular mortality, and all-cause mortality (all P values < 0.001). Furthermore, both Kaplan-Meier method and Categorical analysis demonstrated that the combined use of sAXL and NT-proBNP were more likely to predict all-cause or cardiovascular mortality (both P < 0.001). Similar results were observed when separating patients with respect to left ventricular ejection fraction, namely, in HFrEF, HFmrEF, and HFpEF groups. CONCLUSIONS: Plasma sAXL concentrations are of great importance in predicting clinical outcomes in HF patients, independent of NT-proBNP, suggesting that sAXL is a promising prognostic marker for further study.

Therapeutic effects of multidisciplinary individualized treatment for COVID-19 patients: the experience of a supporting medical team in Wuhan.

Background: The sudden outbreak of coronavirus disease 2019 (COVID-19) has brought people around the world into an abyss of suffering. At that time, there were no clear and effective means for the treatment of the virus. We prepared a medical team consisted of specialists in critical care, respiratory diseases, infections, gastroenterology, endocrinology, cardiology, cerebrovascular diseases, nephrology, rehabilitation, psychology, and nutrition. This study shared our multidisciplinary treatment experience in treating patients with COVID-19. Methods: Patients with positive SARS-CoV-2 swab test were divided into three groups: ordinary cases, severe cases and critical cases. Every patient received the multi-disciplinary comprehensive and individualized tailored treatment based on the specific situation of each patient. Patients' medical records, epidemiological, clinical, laboratory, radiological characteristics, Borg dyspnea score, Barthel index, self-rating anxiety scale (SAS) as well as treatment and outcome data were analyzed. Results: The mean age of the 90 patients was 61.88±15.25 years. Some patients without underlying disease had developed comorbidities such as hyperglycemia (24, 26.67%) and hypertension (9, 10%). With multidisciplinary individualized treatment, the patients' albumin level and Barthel index score increased significantly, while glucose level, blood pressure, and Nutrition Risk Screening 2002 (NRS-2002), Borg scale, and SAS values significantly decreased at discharge. The in-hospital mortality rate was 4.44%. However, there was still a gap in Nutrition Risk Screening, Borg dyspnea score and Barthel index between the critical cases and the ordinary and severe cases at discharge. We observed that the patients with more severe disease had significantly higher age, rates of hypertension, and mortality. The median hospitalization time of discharged patients was 19 days [interquartile range (IQR), 9.0-20.0 days]. Conclusions: Multidisciplinary collaboration and individualized treatment could effectively improve the general status of patients with different severity of COVID-19.

The Association and Pathogenesis of SERPINA3 in Coronary Artery Disease.

Background: Serine proteinase inhibitor A3 (SERPINA3) has been discovered in the pathogenesis of many human diseases, but little is known about the role of SERPINA3 in coronary artery disease (CAD). Therefore, we aim to determine its relationship with CAD and its function in the pathogenesis of atherosclerosis. Methods: In total 86 patients with CAD and 64 patients with non-CAD were compared. The plasma SERPINA3 levels were measured using ELISA. Logistic regression analysis and receiver-operating characteristic (ROC) analysis were performed to illustrate the association between plasma SERPINA3 levels and CAD. In vitro, real-time PCR (RT-PCR) and immunofluorescence staining were used to determine the expression of SERPINA3 in atherosclerotic plaques and their component cells. Then rat aortic smooth muscle cells (RASMCs) were transfected with siRNA to knock down the expression of SERPINA3 and human umbilical vein endothelial cells (HUVECs) were stimulated by SERPINA3 protein. EdU assay and scratch assay were used for assessing the capability of proliferation and migration. The cell signaling pathway was evaluated by western blot and RT-PCR. Results: Patients with CAD [104.4(54.5-259.2) µg/mL] had higher levels of plasma SERPINA3 than non-CAD [65.3(47.5-137.3) µg/mL] (P = 0.004). After being fully adjusted, both log-transformed and tertiles of plasma SERPINA3 levels were significantly associated with CAD. While its diagnostic value was relatively low since the area under the ROC curve was 0.64 (95% CI: 0.55-0.73). Secreted SERPINA3 might increase the expression of inflammatory factors in HUVECs. Vascular smooth muscle cells had the highest SERPINA3 expression among the aorta compared to endothelial cells and inflammatory cells. The knockdown of SERPINA3 in RASMCs attenuated its proliferation and migration. The phosphorylated IκBα and its downstream pathway were inhibited when SERPINA3 was knocked down. Conclusions: Elevated plasma SERPINA3 levels were associated with CAD. SERPINA3 can increase inflammatory factors expression in HUVECs. It can regulate VSMCs proliferation, migration, and releasing of inflammatory factors through the NF-κB signaling pathway. Thus, SERPINA3 played a significant role in the pathogenesis of atherosclerosis.

Circulating miR-19b-3p as a Novel Prognostic Biomarker for Acute Heart Failure.

Background Circulating microRNAs are emerging biomarkers for heart failure (HF). Our study aimed to assess the prognostic value of microRNA signature that is differentially expressed in patients with acute HF. Methods and Results Our study comprised a screening cohort of 15 patients with AHF and 5 controls, a PCR-discovery cohort of 50 patients with AHF and 26 controls and a validation cohort of 564 patients with AHF from registered study DRAGON-HF (Diagnostic, Risk Stratification and Prognostic Value of Novel Biomarkers in Patients With Heart Failure). Through screening by RNA-sequencing and verification by reverse-transcription quantitative polymerase chain reaction, 9 differentially expressed microRNAs were verified (miR-939-5p, miR-1908-5p, miR-7706, miR-101-3p, miR-144-3p, miR-4732-3p, miR-3615, miR-484 and miR-19b-3p). Among them, miR-19b-3p was identified as the microRNA signature with the highest fold-change of 8.4 and the strongest prognostic potential (area under curve with 95% CI, 0.791, 0.654-0.927). To further validate its prognostic value, in the validation cohort, the baseline level of miR-19b-3p was measured. During a follow-up period of 19.1 (17.7, 20.7) months, primary end point comprising of all-cause mortality or readmission due to HF occurred in 48.9% patients, while patients in the highest quartile of miR-19b-3p level presented the worst survival (Log-rank P<0.001). Multivariate Cox model showed that the level of miR-19b-3p could independently predict the occurrence of primary end point (adjusted hazard ratio,1.39; 95% CI, 1.18-1.64). In addition, miR-19b-3p positively correlated with soluble suppression of tumorigenicity 2 and echocardiographic indexes of left ventricular hypertrophy. Conclusions Circulating miR-19b-3p could be a valuable prognostic biomarker for AHF. In addition, a high level of circulating miR-19b-3p might indicate ventricular hypertrophy in AHF subjects. Registration URL: https://www.clinicaltrials.gov. Unique Identifier: NCT03727828.

The relationship between amylopectin fine structure and the physicochemical properties of starch during potato growth.

The aim of this study was to explore the relationship between the structural and functional properties of starch isolated from Atlantic potatoes at different stages of growth without the effect of varieties and growth environment. The molecular size and chain-length distribution of amylopectin significantly varied with growth. The Mw and Mn of amylopectin ranged from 2.976 × 107 to 4.512 × 107 g/mol and 1.275 × 107 to 2.295 × 107 g/mol, respectively, suggested that the polydispersity varied with growth. The average chain length of amylopectin during potato growth showed small but significant changes and ranged from DP 23.59 to 24.73. Overall, Afp chains, Acrystal chains, and B1 chains increased with growth, and B2 and B3 chains decreased with growth. There was wide variation in starch pasting, gelatinization, retrogradation, in vitro starch digestibility, swelling power, solubility, and gel stability properties. Specifically, potato starch harvested at the earliest time had the highest resistant starch content. The variation trend of swelling power and solubility was similar, reached highest value at 42 days, were 20.38 g/g and 8.83%, respectively. Correlation analysis revealed that the physicochemical properties were significantly affected by amylopectin fine structure. The results of this study enhance our understanding of the structure-function relationship of potato starch.

Prognostic value of serum hyponatremia for outcomes in patients with heart failure with preserved ejection fraction: An observational cohort study.

Hyponatremia is a risk factor associated with poor prognosis in patients with heart failure (HF) with reduced ejection fraction. However, whether hyponatremia has a similar role in patients with HF with preserved ejection fraction (HFpEF) has remained controversial. Therefore, the present study aimed to investigate the clinical characteristics and 24-month prognostic profile of a cohort of patients with HFpEF in China. From a registered observational cohort study on 1,027 subjects with HF, 496 patients with HFpEF were included. The association between baseline hyponatremia on admission and 24-month adverse outcomes (including all-cause mortality, re-hospitalization for HF and stroke) was analyzed using logistic regression with the Cox proportional hazards model. Of the 496 patients with HFpEF with a mean age of 72.8 years and proportion of males of 53.0%, 71 patients were diagnosed with hyponatremia. Furthermore, 29 patients (5.8%) were lost to follow-up. The hyponatremia group had lower blood pressure and serum hemoglobin, higher N-terminal pro B-type natriuretic peptide (NT-proBNP) and D-dimer, more patients with a history of atrial fibrillation and a higher proportion of spironolactone and loop diuretic use. According to a multivariate regression analysis, New York Heart Association functional classes III-IV and a serum NT-proBNP level above the median were risk factors for hyponatremia, while higher systolic blood pressure and ß-blocker use were protective factors against hyponatremia. In the Kaplan-Meier analysis, hyponatremia was associated with all-causes of mortality, re-hospitalization for HF and a poor prognosis for patients suffering from strokes (log-rank P<0.05 for all 3 endpoints). On multivariate logistic regression analysis with the Cox proportional hazard model, hyponatremia was an independent predictor of three adverse outcomes [all-cause mortality: Hazard ratio (HR)=1.54, 95% CI=1.07-2.91, P=0.034; re-hospitalization for heart failure: HR=1.28, 95% CI=1.16-2.47, P=0.013; stroke: HR=1.78, 95% CI=1.04-2.89, P=0.016]. Collectively, the present results suggested that hyponatremia on admission was significantly associated with all-cause mortality, re-hospitalization and stroke within 24 months in a cohort of hospitalized patients with HFpEF in China. Thus, hyponatremia should be carefully monitored and frequently adjusted in patients with HFpEF (NCT04062500).

Predictive value of left atrial appendage lobes on left atrial thrombus or spontaneous echo contrast in patients with non-valvular atrial fibrillation.

BACKGROUND: Left atrial appendage morphology has been proved to be an important predictor of left atrial thrombus (LAT) and left atrial spontaneous echo contrast (LASEC) and stroke in patients with non-valvular atrial fibrillation (NVAF). However, the relation between left atrial appendage (LAA) lobes and LAT or LASEC is still unknown. The aim of this study is to investigate the correlation between the number of left atrial appendage lobes and LAT/LASEC in patients with NVAF. METHODS: This monocentric cross-sectional study enrolled 472 consecutive patients with non-valvular atrial fibrillation, who had transthoracic echocardiography (TTE) and transesophageal echocardiography (TEE) prior to cardioversion or left atrial appendage closure (LAAC) from July 2009 to August 2015 in department of cardiology of Shanghai Tenth People's Hospital. Patients who had significant mitral or aortic valve disease, previous cardiac valvular surgery and other complicated cardiac diseases were excluded. Individuals were divided into two groups:the LAT/LASEC group (16.95%), which comprised patients with LAT or LASEC, as confirmed by TEE; and a negative control group (83.05%).Baseline overall group characterization with demographic, clinical, laboratory data and echocardiographic parameters, alongside with information on medication was obtained for all patients. Subgroup analysis with line chart was applied for exploring the association between LAA lobes and LAT/LAESC. Receptor-operating curves (ROC) were used to test the value of LA anteroposterior diameter detected by different echocardiography methods predicting LAT or LASEC. Multivariable logistic regression analysis was used to investigate independent predictors of LAT/LASEC. RESULTS: Among 472 patients, 23 (4.87%) had LA/LAA thrombus and 57 (12.1%) had LA spontaneous echo contrast. Compared to the negative group, patients in LAT/LASEC group had higher CHA2DS2-VASc score (3.79 ± 1.75 vs 2.65 ± 1.76, p < 0.001), larger LAD (measured by TTE, 48.1 ± 7.7 vs 44.6 ± 6.5, P < 0.001; measured by TEE, 52.2 ± 6.2 vs 46.7 ± 7.1, P < 0.001), lower left upper pulmonary venous flow velocity (LUPVFV) (0.54 ± 0.17 m/s vs 0.67 ± 0.26 m/s, CI 95% 0.05-0.22, P = 0.003), more left atrial appendage lobes (1.67 ± 0.77 vs 1.25 ± 0.50, p < 0.001). There was a good discriminative capacity for LAD detected by TTE (area under the curve (AUC), 0.67, CI 95% 0.61-0.73, p < 0.001) and LAD detected by TEE (AUC, 0.73, CI 95% 0.67-0.79, p < 0.001). The subgroup analysis based on gender and different LAA lobes yielded similar results (male group: p < 0.001;female group: p = 0.004) that the number of LAA lobes were significantly associated with LA thrombus or SEC. In multivariable logistic regression analysis, both the number of LAA lobes (odds ratio: 2.37; CI 95% 1.37-4.09; p = 0.002) and the persistent AF (odds ratio: 3.57; CI 95% 1.68-7.57; p = 0.001) provided independent and incremental predictive value beyond CHA2DS2-VASc score. CONCLUSION: The number of LAA lobes is an independent risk factor and has a moderate predictive value for LAT/LASEC among NVAF patients in China.

The differential expression of novel circular RNAs in an acute lung injury rat model caused by smoke inhalation

Acute lung injury caused by smoke inhalation is a common severe clinical syndrome. This study aimed to investigate the potential expression of circular RNAs during acute lung injury triggered by smoke inhalation. The acute lung injury rat model was established with smoke inhalation from a self-made smoke generator. The occurrence of acute lung injury was validated by an analysis of the bronchoalveolar lavage fluid and hematoxylin-eosin (HE) staining of lung tissues. Next-generation sequencing and quantitative PCR were performed to identify the differentially expressed circular RNAs associated with acute lung injury that was caused by smoke inhalation. The circular form of the identified RNAs was finally verified by multiple RT-PCR-based assays. The bronchoalveolar lavage fluid (BALF) and lung tissue analysis showed that smoke inhalation successfully induced acute injury in rats, as evidenced by the significantly altered cell numbers, including macrophages, neutrophils, and red blood cells, disrupted cell lining, and increased levels of interleukin-1β, tumor necrosis factor-alpha, and IL-8 in lung tissues. Ten significantly differentially expressed circular RNAs were identified with next-generation sequencing and RT-PCR. The circular form of these RNAs was verified by multiple RT-PCR-based assays. In conclusion, the identified circular RNAs were prevalently and differentially expressed in rat lungs after acute lung injury caused by smoke inhalation

The differential expression of novel circular RNAs in an acute lung injury rat model caused by smoke inhalation.

Acute lung injury caused by smoke inhalation is a common severe clinical syndrome. This study aimed to investigate the potential expression of circular RNAs during acute lung injury triggered by smoke inhalation. The acute lung injury rat model was established with smoke inhalation from a self-made smoke generator. The occurrence of acute lung injury was validated by an analysis of the bronchoalveolar lavage fluid and hematoxylin-eosin (HE) staining of lung tissues. Next-generation sequencing and quantitative PCR were performed to identify the differentially expressed circular RNAs associated with acute lung injury that was caused by smoke inhalation. The circular form of the identified RNAs was finally verified by multiple RT-PCR-based assays. The bronchoalveolar lavage fluid (BALF) and lung tissue analysis showed that smoke inhalation successfully induced acute injury in rats, as evidenced by the significantly altered cell numbers, including macrophages, neutrophils, and red blood cells, disrupted cell lining, and increased levels of interleukin-1ß, tumor necrosis factor-alpha, and IL-8 in lung tissues. Ten significantly differentially expressed circular RNAs were identified with next-generation sequencing and RT-PCR. The circular form of these RNAs was verified by multiple RT-PCR-based assays. In conclusion, the identified circular RNAs were prevalently and differentially expressed in rat lungs after acute lung injury caused by smoke inhalation.

MEF2C loss-of-function mutation contributes to congenital heart defects.

Congenital heart disease (CHD) is the most common type of developmental abnormality in humans, and is a leading cause for substantially increased morbidity and mortality in affected individuals. Increasing studies demonstrates a pivotal role of genetic defects in the pathogenesis of CHD, and presently mutations in more than 60 genes have been associated with CHD. Nevertheless, CHD is of pronounced genetic heterogeneity, and the genetic basis underpinning CHD in a large proportion of patients remains unclear. In the present study, the whole coding exons and splicing donors/acceptors of the MEF2C gene, which codes for a transcription factor essential for normal cardiovascular development, were sequenced in 200 unrelated patients affected with CHD, and a novel heterozygous missense mutation, p.L38P, was identified in an index patient with patent ductus arteriosus (PDA) and ventricular septal defect (VSD). Genetic scan of the mutation carrier's family members available showed that the mutation was present in all affected family members but absent in unaffected family members. Analysis of the proband's pedigree revealed that the mutation co-segregated with PDA, which was transmitted as an autosomal dominant trait with complete penetrance. The mutation changed the amino acid that was completely conserved evolutionarily, and did not exist in 300 unrelated, ethnically-matched healthy individuals used as controls. Functional deciphers by using a dual-luciferase reporter assay system unveiled that the mutant MEF2C protein had a significantly reduced transcriptional activity. Furthermore, the mutation significantly diminished the synergistic activation between MEF2C and GATA4, another cardiac core transcription factor that has been causally linked to CHD. In conclusion, this is the first report on the association of a MEF2C loss-of-function mutation with an increased vulnerability to CHD in humans, which provides novel insight into the molecular mechanisms underlying CHD, implying potential implications for early diagnosis and timely prophylaxis of CHD.

PITX2 Loss-of-Function Mutation Contributes to Congenital Endocardial Cushion Defect and Axenfeld-Rieger Syndrome.

Congenital heart disease (CHD), the most common type of birth defect, is still the leading non-infectious cause of infant morbidity and mortality in humans. Aggregating evidence demonstrates that genetic defects are involved in the pathogenesis of CHD. However, CHD is genetically heterogeneous and the genetic components underpinning CHD in an overwhelming majority of patients remain unclear. In the present study, the coding exons and flanking introns of the PITX2 gene, which encodes a paired-like homeodomain transcription factor 2essential for cardiovascular morphogenesis as well as maxillary facial development, was sequenced in 196 unrelated patients with CHD and subsequently in the mutation carrier's family members available. As a result, a novel heterozygous PITX2 mutation, p.Q102X for PITX2a, or p.Q148X for PITX2b, or p.Q155X for PITX2c, was identified in a family with endocardial cushion defect (ECD) and Axenfeld-Rieger syndrome (ARS). Genetic analysis of the pedigree showed that the nonsense mutation co-segregated with ECD and ARS transmitted in an autosomal dominant pattern with complete penetrance. The mutation was absent in 800 control chromosomes from an ethnically matched population. Functional analysis by using a dual-luciferase reporter assay system revealed that the mutant PITX2 had no transcriptional activity and that the mutation eliminated synergistic transcriptional activation between PITX2 and NKX2.5, another transcription factor pivotal for cardiogenesis. To our knowledge, this is the first report on the association of PITX2 loss-of-function mutation with increased susceptibility to ECD and ARS. The findings provide novel insight into the molecular mechanisms underpinning ECD and ARS, suggesting the potential implications for the antenatal prophylaxis and personalized treatment of CHD and ARS.

TBX5 loss-of-function mutation contributes to familial dilated cardiomyopathy.

The cardiac T-box transcription factor TBX5 is crucial for proper cardiovascular development, and mutations in TBX5 have been associated with various congenital heart diseases and arrhythmias in humans. However, whether mutated TBX5 contributes to dilated cardiomyopathy (DCM) remains unclear. In this study, the coding exons and flanking introns of the TBX5 gene were sequenced in 190 unrelated patients with idiopathic DCM. The available family members of the index patient carrying an identified mutation and 200 unrelated ethnically matched healthy individuals used as controls were genotyped for TBX5. The functional characteristics of the mutant TBX5 were explored in contrast to its wild-type counterpart by using a dual-luciferase reporter assay system. As a result, a novel heterozygous TBX5 mutation, p.S154A, was identified in a family with DCM inherited in an autosomal dominant pattern, which co-segregated with DCM in the family with complete penetrance. The missense mutation was absent in 400 control chromosomes and the altered amino acid was completely conserved evolutionarily across various species. Functional assays revealed that the mutant TBX5 had significantly decreased transcriptional activity. Furthermore, the mutation markedly diminished the synergistic activation of TBX5 with NKX2-5 or GATA4, other two transcription factors causatively linked to DCM. This study firstly associates TBX5 loss-of-function mutation with enhanced susceptibility to DCM, providing novel insight into the molecular mechanisms of DCM, and suggesting the potential implications in the development of new treatment strategies for this common form of myocardial disorder.

GATA5 loss-of-function mutation in familial dilated cardiomyopathy.

Dilated cardiomyopathy (DCM), the most common form of primary myocardial disease, is an important cause of sudden cardiac death and heart failure and is the leading indication for heart transplantation in children and adults worldwide. Recent studies have revealed a strong genetic basis for idiopathic DCM, with many distinct genes causally implicated. Nevertheless, DCM is a genetically heterogeneous disorder and the genetic determinants underlying DCM in a substantial proportion of patients remain unclear. In this study, the whole coding exons and flanking introns of the GATA binding protein 5 (GATA5) gene, which codes for a zinc-finger transcription factor essential for cardiovascular development and structural remodeling, were sequenced in 130 unrelated patients with idiopathic DCM. The available relatives of the index patient carrying an identified mutation and 200 unrelated ethnically matched healthy individuals used as the controls were genotyped for GATA5. The functional characteristics of the mutant GATA5 were analyzed in contrast to its wild-type counterpart by using a dual-luciferase reporter assay system. As a result, a novel heterozygous GATA5 mutation, p.G240D, was identified in a family with DCM inherited in an autosomal dominant pattern, which co-segregated with DCM in the family with complete penetrance. The missense mutation was absent in 400 reference chromosomes and the altered amino acid was completely conserved evolutionarily across species. Functional analyses revealed that the GATA5 mutant was associated with significantly diminished transcriptional activity. This study firstly links GATA5 mutation to DCM, which provides novel insight into the molecular mechanisms of DCM, suggesting a potential molecular target for the prenatal prophylaxis and allele-specific treatment of DCM.

A novel NKX2.5 loss-of-function mutation associated with congenital bicuspid aortic valve.

Bicuspid aortic valve (BAV) is the most common form of congenital cardiovascular defect in humans and is associated with substantial morbidity and mortality. Emerging evidence demonstrates that genetic risk factors play an important role in the pathogenesis of BAV. However, BAV is a genetically heterogenous disorder, and the genetic defects underpinning BAV in most patients remain to be identified. In the present study, the coding exons and flanking introns of the NKX2.5 gene, which encodes a homeodomain-containing transcription factor essential for the normal development of the aortic valve, were sequenced in 142 unrelated patients with BAV. The available relatives of the mutation carrier and 200 unrelated healthy subjects used as controls were also genotyped for NKX2.5. The functional characteristics of the mutation were delineated by using a dual-luciferase reporter assay system. As a result, a novel heterozygous NKX2.5 mutation, p.K192X, was identified in a family with BAV transmitted in an autosomal dominant pattern. The nonsense mutation was absent in 400 control chromosomes. Functional analyses revealed that the mutant NKX2.5 had no transcriptional activity compared with its wild-type counterpart. Furthermore, the mutation abolished the synergistic transcriptional activation between NKX2.5 and GATA5, another transcription factor crucial for the aortic valvular morphogenesis. In conclusion, this study is the first to link an NKX2.5 loss-of-function mutation to enhanced susceptibility to human BAV, providing novel insight into the molecular mechanism of BAV and suggesting potential implications for genetic counseling and clinical care of families presenting with BAV.

Correlation between functional status and quality of life after surgery in patients with primary malignant bone tumor of the lower extremities.

PURPOSE: This study aims to explore the correlation between functional status and quality of life after surgery in patients with primary malignant bone tumor of the lower extremities. METHODS: A total of 94 patients with primary malignant bone tumor of the lower extremities were enrolled. Correlations between their functional status and quality of life after surgery were descriptively analyzed through functional mobility assessment, Toronto extremity salvage scaling, reintegration to normal life index, and the 36-item Short Form Health Survey. RESULTS: All patients presented decreased physical function, activities of daily life (ADL), and social participation capability. Their quality of life was significantly lower than the norm. Scores under all items of functional status significantly correlated with the quality-of-life score (r = .265-.427; p < .01). The postoperative functional status of patients with primary malignant bone tumor of the lower extremities greatly influences quality of life. Lower levels of physical function, ADL, and social participation indicate poorer quality of life. CONCLUSION: To improve quality of life, necessary nursing measures should be adopted to intervene with postoperative functional rehabilitation processes.

APACHE IV is superior to MELD scoring system in predicting prognosis in patients after orthotopic liver transplantation.

This study aims to compare the efficiency of APACHE IV with that of MELD scoring system for prediction of the risk of mortality risk after orthotopic liver transplantation (OLT). A retrospective cohort study was performed based on a total of 195 patients admitted to the ICU after orthotopic liver transplantation (OLT) between February 2006 and July 2009 in Guangzhou, China. APACHE IV and MELD scoring systems were used to predict the postoperative mortality after OLT. The area under the receiver operating characteristic curve (AUC) and the Hosmer-Lemeshow C statistic were used to assess the discrimination and calibration of APACHE IV and MELD, respectively. Twenty-seven patients died during hospitalization with a mortality rate of 13.8%. The mean scores of APACHE IV and MELD were 42.32 ± 21.95 and 18.09 ± 10.55, respectively, and APACHE IV showed better discrimination than MELD; the areas under the receiver operating characteristic curve for APACHE IV and MELD were 0.937 and 0.694 (P < 0.05 for both models), which indicated that the prognostic value of APACHE IV was relatively high. Both models were well-calibrated (The Hosmer-Lemeshow C statistics were 1.568 and 6.818 for APACHE IV and MELD, resp.; P > 0.05 for both). The respective Youden indexes of APACHE IV, MELD, and combination of APACHE IV with MELD were 0.763, 0.430, and 0.545. The prognostic value of APACHE IV is high but still underestimates the overall hospital mortality, while the prognostic value of MELD is poor. The function of the APACHE IV is, thus, better than that of the MELD.

Bi-functional ZnO-RGO-Au substrate: photocatalysts for degrading pollutants and SERS substrates for real-time monitoring.

A ZnO-RGO-Au composite with bi-functional behavior was fabricated: it was employed both as a photocatalyst for degrading pollutants (Rhodamine 6G) and a SERS substrate for real-time monitoring of the degradation quantitatively.

Association of angiotensin-converting enzyme gene I/D and CYP11B2 gene -344T/C polymorphisms with lone atrial fibrillation and its recurrence after catheter ablation.

The renin-angiotensin-aldosterone system (RAAS) plays a key role in atrial structural and electrical remodeling. The aim of this study was to investigate the potential associations of angiotensin-converting enzyme (ACE) gene insertion/ deletion (I/D) and aldosterone synthase (CYP11B2) gene -344T/C polymorphisms with the risk and recurrence of lone atrial fibrillation (AF). One hundred and ninety-three patients who underwent successful catheter ablation for lone AF were recruited. Two hundred and ninety-seven sinus rhythm subjects without a history of arrhythmia served as controls. The subjects were genotyped for ACE gene I/D and CYP11B2 gene -344T/C polymorphisms. Results showed that the ACE gene DD genotype and D allele were associated with a greater prevalence of lone AF (both P<0.01). In addition, the ACE gene DD genotype had a significantly larger left atrial dimension (LAD; 41.6±5.7 mm vs. 39.6±5.2 mm; P=0.043) and higher risk of AF recurrence [44.7% vs. 23.2%; odds ratio (OR), 2.68; 95% confidence interval (CI), 1.28-5.61; P=0.008] compared with the II+ID genotype in lone AF patients. After adjustment for a variety of risk factors, the ACE gene DD genotype had a 1.97-fold increased risk for lone AF (OR, 1.97; 95% CI, 1.15-3.37; P= 0.013) and 2.35-fold increased risk for AF recurrence (RR, 2.35; 95% CI, 1.10-5.04; P=0.028) compared with the ACE gene II+ID genotype. However, no correlation between the CYP11B2 gene -344T/C polymorphism and lone AF or its recurrence was observed in this cohort. In conclusion, the ACE gene DD genotype was associated with an increased incidence of lone AF and its recurrence following ablation, which was partly mediated by LAD.