Target organ damage in untreated hypertensive patients with primary aldosteronism.

An increased risk of target organ damage (TOD) has been reported in patients with primary aldosteronism (PA). However, there is relatively little related research on the correlation between the degree of TOD and those with and without PA in newly diagnosed hypertensive patients. The aim of this study was to assess the association between PA and TOD among patients with newly diagnosed hypertension. Newly diagnosed hypertensive patients were consecutively recruited from January 2015 to June 2020 at the University of Hong Kong-Shenzhen Hospital. Patients were stratified into those with and without PA. Data for left ventricular mass index (LVMI), carotid intima-media thickness (CIMT) and plaque, and microalbuminuria were systematically collected. A total of 1044 patients with newly diagnosed hypertension were recruited, 57 (5.5%) of whom were diagnosed with PA. Patients with PA had lower blood pressure, serum lipids, body mass index, and plasma renin activity and a higher incidence of hypokalemia than those without PA. In contrast, the prevalence of left ventricular hypertrophy, increased CIMT, and microalbuminuria was higher in patients with PA than in those without PA. Multivariable regression analysis demonstrated that PA was independently associated with increased LVMI, CIMT and microalbuminuria. Among patients with newly diagnosed hypertension, those with PA had more severe TOD, including a higher LVMI, CIMT and microalbuminuria, than those without PA. These findings emphasize the need for screening TOD in newly diagnosed hypertension due to underlying PA.

Association of serum uric acid with biventricular myocardial dysfunction in patients with type 2 diabetes mellitus.

BACKGROUND AND AIMS: Increased serum uric acid (SUA) is common in type 2 diabetes mellitus (T2DM) and is associated with left ventricular (LV) myocardial dysfunction. Nonetheless the association of SUA with right ventricular (RV) function in T2DM has not been studied. This study aimed to investigate the association of SUA with biventricular myocardial function in patients with T2DM. METHODS AND RESULTS: A total of 560 patients with T2DM were enrolled and divided into four groups according to sex-specific quartiles of SUA. Transthoracic echocardiography was performed and two-dimensional speckle tracking was used to measure biventricular myocardial strain, including LV global longitudinal strain (GLS), circumferential strain (CS), radial strain (RS), and RV free wall longitudinal strain (RV-FWLS). The absolute value of all biventricular strain parameters showed a stepwise decrease across SUA quartiles (all P < 0.01). In particular, LV assessment by GLS, CS and RS demonstrated that those in the 4th quartile were impaired compared with the other quartiles (all P < 0.05). Similarly, RV-FWLS of the 4th quartile was significantly impaired compared with the 1st and 2nd quartiles (all P < 0.05). The same reduction in biventricular strain across SUA quartiles was observed in patients with estimated glomerular filtration rate < or ≥60 ml/min/1.73 m2, and glycated hemoglobin < or ≥7.0% (all P < 0.05). Multivariable linear regression analysis demonstrated that higher quartile of SUA was independently associated with impaired biventricular myocardial strain (all P < 0.05). CONCLUSIONS: SUA was independently associated with biventricular myocardial dysfunction in asymptomatic T2DM patients, regardless of renal function or diabetic control.

Sex-specific pattern of left ventricular hypertrophy and diastolic function in patients with type 2 diabetes mellitus.

AIMS: Few prospective studies have evaluated sex-specific pattern, natural progression of left ventricular (LV) remodelling, and diastolic dysfunction in patients with type 2 diabetes (T2DM). The aim of this study was to study the sex-specific prevalence, longitudinal changes of LV remodelling, and diastolic dysfunction in patients with T2DM. Further, the prognostic value of diastolic function in women and men was also evaluated. METHODS AND RESULTS: A total of 350 patients with T2DM (mean age 61 ± 11 years; women, 48.3%) was recruited. Detailed echocardiography was performed at baseline and after 25 months. A major adverse cardiovascular event (MACE) was defined as cardiovascular death, heart failure hospitalization, or myocardial infarction. Despite a similar age, prevalence of hypertension and body mass index, women had a higher prevalence of LV hypertrophy and diastolic dysfunction at baseline and follow-up compared with men. A total of 21 patients developed MACE (5 cardiovascular death, 9 hospitalization for heart failure, and 7 myocardial infarction) during a median follow-up of 56 months. Women with diastolic dysfunction had a higher incidence of MACE than those with normal diastolic function but this association was neutral in men. Multivariable Cox-regression analysis indicated that diastolic dysfunction was associated with MACE in women [hazard ratio = 6.30; 95% confidence interval (CI) = 1.06-37.54; P < 0.05] but not men (hazard ratio = 2.29, 95% CI = 0.67-7.89; P = 0.19). CONCLUSION: LV hypertrophy and diastolic dysfunction, both at baseline and follow-up, were more common in women than men. Pre-clinical diastolic dysfunction was independently associated with MACE only in women with T2DM but was neutral in men.

Abnormal mitral-aortic intervalvular coupling in mitral valve diseases: a study using real-time three-dimensional transesophageal echocardiography.

BACKGROUND: Mitral and aortic valves are coupled via fibrous tissue. This coupling is considered to be important for cardiac function before and after mitral valve surgery. The relationship between mitral-aortic coupling and different types of mitral regurgitation (MR) is not completely understood. METHODS AND RESULTS: Real-time three-dimensional transesophageal echocardiography (RT3D-TEE) was performed in 133 subjects: 30 normal subjects, 15 patients with Carpentier type I MR (annular dilatation and congenital cleft), 40 type II (mitral valve prolapse), 20 type IIIa (rheumatic) and 28 type IIIb (ischemic mitral regurgitation). Custom software was used to track mitral (MA) and aortic annuli (AoA) in 3D space throughout cardiac cycle, allowing measurement of changes in mitral and aortic valve morphology. Normal mitral-aortic coupling is characterized by reciprocal changes in the annular areas throughout cardiac cycle, with systolic reduction of the angle between the two annular planes. In Carpentier type II patients, not only MA but also AoA areas were increased (P < 0.05 vs normal), but the reciprocal pattern of mitral-aortic coupling was preserved. In both type I IMR and IIIb patients, MA and AoA areas were both increased (P < 0.05 vs normal) and the reciprocal behavior of mitral-aortic coupling was lost. Only MA area was increased in type IIIa patients. The extent of mitral-aortic angle reduction during systole was diminished in all 4 Carpentier groups (P < 0.05 vs normal). CONCLUSIONS: Mitral valve diseases may affect normal mitral-aortic coupling and aortic valve function. Different patterns of abnormal mitral-aortic coupling are associated with different Carpentier types of MR.

Dynamic assessment of the changing geometry of the mitral apparatus in 3D could stratify abnormalities in functional mitral regurgitation and potentially guide therapy.

INTRODUCTION: In functional mitral regurgitation (FMR), effective regurgitant orifice area (EROA) displays a dynamic pattern. The impact of dynamic changes of annulus dysfunction and leaflets tenting on phasic EROA was explored with real-time three-dimensional transesophageal echocardiography (RT3D-TEE). METHODS: RT3D-TEE was performed in 52 FMR patients and 30 controls. Mitral annulus dimensions and leaflets tenting were measured throughout systole (TomTec, Germany). Phasic EROA was measured by proximal isovelocity surface area (PISA) method. RESULTS: Mitral annulus had the minimal area and an oval shape with saddle configuration during early systole in controls, which enlarged and became round and flattened towards mid and late systole (P<0.05). In contrast, annulus in FMR was significantly larger, rounder and flatter (P<0.001), which further dilated and became more flattened at late systole (P<0.05 vs control). Leaflet tenting height in FMR decreased in mid systole and remains unchanged towards late systole. The leaflet tenting volume peaked at early and late systole with a mid-systolic trough in both FMR and controls. But tenting volume of patients with FMR was significantly larger than that of controls (all P<0.001 vs control in whole systole). Further analysis demonstrated that early tenting volume (ß value=0.053, P<0.05) was a predictor of early EROA, whereas late tenting volume (ß value=0.031, P<0.05) and late annular displacement velocity were predictors of late EROA. CONCLUSIONS: The early and late peak EROAs of FMR was primarily contributed by tenting volume at early systole and late systole respectively. These findings would be of value to consider in interventions aimed at reducing the severity of FMR.

Disruption of secondary wall cellulose biosynthesis alters cadmium translocation and tolerance in rice plants.

Tricheary elements (TEs), wrapped by secondary cell wall, play essential roles in water, mineral, and nutrient transduction. Cadmium (Cd) is a toxic heavy metal that is absorbed by roots and transported to shoot, leaves, and grains through vascular systems in plants. As rice is a major source of Cd intake, many efforts have been made to establish 'low-Cd rice'. However, no links have been found between cellulose biosynthesis and cadmium accumulation. We report here a rice brittle culm13 mutant, resulting from a novel missense mutation (E101K) [corrected] in the N-terminus of cellulose synthase subunit 9 (CESA9). Except for the abnormal mechanical strength, the mutant plants are morphologically indistinguishable from the wild-type plants. Transmission electron microscopy (TEM) and chemical analyses showed a slight reduction in secondary wall thickness and 22% decrease in cellulose content in bc13 plants. Moreover, this mutation unexpectedly confers the mutant plants Cd tolerance due to less Cd accumulation in leaves. Expression analysis of the genes required for Cd uptake and transport revealed complicated alterations after applying Cd to wild-type and bc13. The mutants were further found to have altered vascular structure. More importantly, Cd concentration in the xylem saps from the bc13 plants was significantly lower than that from the wild-type. Combining the analyses of CESA9 gene expression and Cd content retention in the cell-wall residues, we conclude that CESA9(E101K) [corrected] mutation alters cell-wall properties in the conducting tissues, which consequently affects Cd translocation efficiency that largely contributes to the low Cd accumulation in the mutant plants.

Quantitative analysis of mitral valve morphology in mitral valve prolapse with real-time 3-dimensional echocardiography: importance of annular saddle shape in the pathogenesis of mitral regurgitation.

BACKGROUND: Few data exist on the relation of the 3-dimensional morphology of mitral valve and degree of mitral regurgitation (MR) in mitral valve prolapse. METHODS AND RESULTS: Real-time 3-dimensional transesophageal echocardiography of the mitral valve was acquired in 112 subjects, including 36 patients with mitral valve prolapse and significant MR (≥3+; MR+ group), 32 patients with mitral valve prolapse but no or mild MR (≤2+; MR- group), 12 patients with significant MR resulting from nonprolapse pathologies (nonprolapse group), and 32 control subjects. The 3-dimensional geometry of mitral valve apparatus was measured with dedicated quantification software. Compared with the normal and MR- groups, the MR+ group had more dilated mitral annulus (P<0.0001), a reduced annular height to commissural width ratio (AHCWR) (P<0.0001) indicating flattening of annular saddle shape, redundant leaflet surfaces (P<0.0001), greater leaflet billow volume (P<0.0001) and billow height (P<0.0001), longer lengths from papillary muscles to coaptation (P<0.0001), and more frequent chordal rupture (P<0.0001). Prevalence of chordal rupture increased progressively with annulus flattening (7% versus 24% versus 42% for AHCWR >20%, 15%-20%, and <15%, respectively; P=0.004). Leaflet billow volume increased exponentially with decreasing AHCWR in patients without chordal rupture (r(2)=0.66, P<0.0001). MR severity correlated strongly with leaflet billow volume (r(2)=0.74, P<0.0001) and inversely with AHCWR (r(2)=0.44, P<0.0001). In contrast, annulus dilatation but not flattening occurred in nonprolapse MR patients. An AHCWR <15% (odds ratio=7.1; P=0.0004) was strongly associated with significant MR in mitral valve prolapse. CONCLUSION: Flattening of the annular saddle shape is associated with progressive leaflet billowing and increased frequencies of chordal rupture and may be important in the pathogenesis of MR in mitral valve prolapse.

Characterization of mid-term atrial geometrical and electrical remodeling following device closure of atrial septal defects in adults.

PURPOSE: Late-onset atrial arrhythmia after successful closure of atrial septal defect (ASD) is not uncommon. Right atrial (RA) enlargement and increased electrocardiographic P-wave dispersion (Pd) independently predict the development of atrial arrhythmia. Data on the degree of right atrial (RA) geometrical and electrical remodeling following device closure of ASD are limited. METHODS: Echocardiography and electrocardiography (ECG) were performed in 58 consecutive patients (47 ± 17 years) before and at 3 months after ASD closure. Persistent RA enlargement was defined as RA volume index (RAVI) ≥ 21 ml/m(2) at 3 months. Pd was calculated as the difference between maximal and minimal P-wave durations in 12-lead ECG. RESULTS: RA size reduced (RAVI: 50 ± 28 vs. 26 ± 16 ml/m(2), p<0.001) and Pd on ECG decreased (53 ± 17 vs. 49 ± 20 ms, p<0.05) significantly at 3 months when compared to baseline. However, persistent RA enlargement remained evident in 31 patients (53%). As a group, they were older with higher pulmonary arterial systolic pressure, larger Qp/Qs, longer maximal P-wave duration and Pd than those with normalized RA. Pd reduction only occurred in patients with normalized RA size. The 3-month Pd (hazard ratio: 1.033, p<0.001) predicted the presence of incomplete RA geometrical remodeling. ROC curve revealed that Pd ≥ 45 ms at 3 months was 77% sensitive and 86% specific in revealing residual RA enlargement. CONCLUSION: Both atrial geometrical and electrical reverse remodeling were evident at 3 months following ASD closure. However, only half of the included patients had normalization of RA size which could be revealed by a simple ECG surrogate of intra-atrial conduction disturbance.

[Mechanisms of subspecies differentiation in a filial generation of rice indica-japonica hybridization under different ecological conditions].

Indica-japonica hybridization is one of the most important breeding methods in China, whereas identifying subspecies differentiation mechanisms is the key in indica-japonica hybridization breeding. By using InDels (Insert/Deletion) and ILPs (Intron Length Polymorphism), an analysis was made on the F6 populations derived from the hybridization of indica-japonica (Qishanzhan/Akihikari) planted in Liaoning and Guangdong provinces and generated by bulk harvesting (BM), single-seed descent methods (SSD), and pedigree method (PM). No segregation distortion was observed for the BM and SSD populations. The frequency distribution of japonica kinship percentage (Dj) was concentrated in 40%-60%. The PM populations in the two provinces presented indica-deviated distribution (30%-55%), with significant difference between Guangdong (38%) and Liaoning (42%). In addition, there was a significant positive correlation between the Dj and the kinship of functional gene regions in the BM and SSD populations. However, part of the positive correlation was broken in the PM populations that showed a regular distribution in the genotype patterns of indica and japonica loci. The above results demonstrated that artificial selection could be the main factor affecting the population differentiation in indica-japonica hybridization, and, with the synergistic effect of natural selection, induced the phenomenon of segregation distortion. There existed a close relationship between the differentiation of subspecies and the important agronomic traits, which could be the main reason why indica-japonica hybridiation breeding could not achieve the expected effect of combining the two subspecies advantages.

[Secretory expression and biological activity analysis of an anti-H5 single-chain antibody from Pichia pastoris].

In our previous study, a panel of 52 broadly cross-reactive H5-specific monoclonal antibodies (MAbs) were generated and characterized. The 13D4, one of these MAbs, has been demonstrated to protect mice against lethal challenge by 4 strains of H5N1 avian influenza virus representing the currently prevailing genetic populations, clades 1, 2.1, 2.2, and 2.3. Here, we further cloned the gene of the 13D4 MAb and constructed a single-chain variable fragment. Then, the 13D4 single-chain antibody (scFv) was expressed in secretory maner in Pichia pastoris. The supernatant of the culture was concentrated and subjected to ammonium sulfate precipitation. The purity of the 13D4 scFv was around 90% in SDS-PAGE following ion-exchange chromatography. We further investigated its binding property using hemagglutination inhibition (HI) test and blocking ELISA. The results indicated that the 13D4 scFv shared the same binding sites and comparable HI titer with the prototype murine 13D4 Mab. In conclusion, an anti-H5 single-chain wide-spectrum neutralizing antibody is prepared successfully in yeast system.