Discovery of TBX20 as a Novel Gene Underlying Atrial Fibrillation.

Atrial fibrillation (AF), the most prevalent type of sustained cardiac dysrhythmia globally, confers strikingly enhanced risks for cognitive dysfunction, stroke, chronic cardiac failure, and sudden cardiovascular demise. Aggregating studies underscore the crucial roles of inherited determinants in the occurrence and perpetuation of AF. However, due to conspicuous genetic heterogeneity, the inherited defects accounting for AF remain largely indefinite. Here, via whole-genome genotyping with genetic markers and a linkage assay in a family suffering from AF, a new AF-causative locus was located at human chromosome 7p14.2-p14.3, a ~4.89 cM (~4.43-Mb) interval between the markers D7S526 and D7S2250. An exome-wide sequencing assay unveiled that, at the defined locus, the mutation in the TBX20 gene, NM_001077653.2: c.695A>G; p.(His232Arg), was solely co-segregated with AF in the family. Additionally, a Sanger sequencing assay of TBX20 in another family suffering from AF uncovered a novel mutation, NM_001077653.2: c.862G>C; p.(Asp288His). Neither of the two mutations were observed in 600 unrelated control individuals. Functional investigations demonstrated that the two mutations both significantly reduced the transactivation of the target gene KCNH2 (a well-established AF-causing gene) and the ability to bind the promoter of KCNH2, while they had no effect on the nuclear distribution of TBX20. Conclusively, these findings reveal a new AF-causative locus at human chromosome 7p14.2-p14.3 and strongly indicate TBX20 as a novel AF-predisposing gene, shedding light on the mechanism underlying AF and suggesting clinical significance for the allele-specific treatment of AF patients.

Analysis of clinical features between active and inactive patients of Takayasu's arteritis with pulmonary arteries involvement.

BACKGROUND: The aim of this study was to investigate the clinical characteristics of patients between active and inactive Takayasu's arteritis with pulmonary artery involvement (PTA) and to identify better markers of disease activity in these patients. METHODS: Sixty-four PTA patients in Beijing Chao-yang hospital (2011 to 2021) were included. According to National Institutes of Health criteria, 29 patients were in active stage and 35 were in inactive stage. Their medical records were collected and analyzed. RESULTS: Compared with inactive group, patients in active group were younger. More patients in active stage presented fever (41.38% vs 5.71%), chest pain (55.17% vs 20%), increased C-reactive protein (2.91 vs 0.46 mg/L), erythrocyte sedimentation rate (35.0 vs 9 mm/h), and platelet count (291 vs 221 × 109/L). Pulmonary artery wall thickening was more common in active group (51.72% vs 11.43%). These parameters were restored after treatment. The incidence of pulmonary hypertension was comparable between groups (34.48% vs 51.43%), but patients in active group had lower pulmonary vascular resistance (PVR) (361.0 vs 891.0 dyn·s·cm-5) and higher cardiac index (2.76 ± 0.72 vs 2.01 ± 0.58 L/min/m2). On multivariate logistic regression analysis, chest pain [odds ratio (OR) 9.37, 95%CI (1.98-44.38), P = 0.005], increased platelet count (>242.5 × 109/L) [OR 9.03, 95%CI (2.10-38.87), P = 0.003] and pulmonary artery wall thickening [OR 7.08, 95%CI (1.44-34.89), P = 0.016] were independently associated with disease activity. CONCLUSION: Chest pain, increased platelet count, and pulmonary artery wall thickening are potential new indicators of disease activity in PTA. Patients in active stage may have lower PVR and better right heart function.

Application of a hospital-community-family trinity rehabilitation nursing model combined with motor imagery therapy in patients with cerebral infarction.

BACKGROUND: Rehabilitation nursing is considered an indispensable part of the cerebral infarction treatment system. The hospital-community-family trinity rehabilitation nursing model can provide continuous nursing services across hospitals, communities, and families for patients. AIM: To explore the application of a hospital-community-family rehabilitation nursing model combined with motor imagery therapy in patients with cerebral infarction. METHODS: From January 2021 to December 2021, 88 patients with cerebral infarction were divided into a study (n = 44) and a control (n = 44) group using a simple random number table. The control group received routine nursing and motor imagery therapy. The study group was given hospital-community-family trinity rehabilitation nursing based on the control group. Motor function (FMA), balance ability (BBS), activities of daily living (BI), quality of life (SS-QOL), activation status of the contralateral primary sensorimotor cortical area to the affected side, and nursing satisfaction were evaluated before and after intervention in both groups. RESULTS: Before intervention, FMA and BBS were similar (P > 0.05). After 6 months' intervention, FMA and BBS were significantly higher in the study than in the control group (both P < 0.05). Before intervention, BI and SS-QOL scores were not different between the study and control group (P > 0.05). However, after 6 months' intervention, BI and SS-QOL were higher in the study than in the control group (P < 0.05). Before intervention, activation frequency and volume were similar between the study and the control group (P > 0.05). After 6 months' intervention, the activation frequency and volume were higher in the study than in the control group (P < 0.05). The reliability, empathy, reactivity, assurance, and tangibles scores for quality of nursing service were higher in the study than in the control group (P < 0.05). CONCLUSION: Combining a hospital-community-family trinity rehabilitation nursing model and motor imagery therapy enhances the motor function and balance ability of patients with cerebral infarction, improving their quality of life.

KLF13 Loss-of-Function Mutations Underlying Familial Dilated Cardiomyopathy.

Background Dilated cardiomyopathy (DCM), characterized by progressive left ventricular enlargement and systolic dysfunction, is the most common type of cardiomyopathy and a leading cause of heart failure and cardiac death. Accumulating evidence underscores the critical role of genetic defects in the pathogenesis of DCM, and >250 genes have been implicated in DCM to date. However, DCM is of substantial genetic heterogeneity, and the genetic basis underpinning DCM remains elusive in most cases. Methods and Results By genome-wide scan with microsatellite markers and genetic linkage analysis in a 4-generation family inflicted with autosomal-dominant DCM, a new locus for DCM was mapped on chromosome 15q13.1-q13.3, a 4.77-cM (≈3.43 Mbp) interval between markers D15S1019 and D15S1010, with the largest 2-point logarithm of odds score of 5.1175 for the marker D15S165 at recombination fraction (θ)=0.00. Whole-exome sequencing analyses revealed that within the mapping chromosomal region, only the mutation in the KLF13 gene, c.430G>T (p.E144X), cosegregated with DCM in the family. In addition, sequencing analyses of KLF13 in another cohort of 266 unrelated patients with DCM and their available family members unveiled 2 new mutations, c.580G>T (p.E194X) and c.595T>C (p.C199R), which cosegregated with DCM in 2 families, respectively. The 3 mutations were absent from 418 healthy subjects. Functional assays demonstrated that the 3 mutants had no transactivation on the target genes ACTC1 and MYH7 (2 genes causally linked to DCM), alone or together with GATA4 (another gene contributing to DCM), and a diminished ability to bind the promoters of ACTC1 and MYH7. Add, the E144X-mutant KLF13 showed a defect in intracellular distribution. Conclusions This investigation indicates KLF13 as a new gene predisposing to DCM, which adds novel insight to the molecular pathogenesis underlying DCM, implying potential implications for prenatal prevention and precision treatment of DCM in a subset of patients.

Responses of leaf functional traits to different hydrological regimes and leaf economics spectrum in the water level fluctuation zone of Three Gorges Reservoir, China.

A unique riparian ecosystem has been created as a result of anti-seasonal flooding after reservoir operations, which notably influences the distribution patterns of plant communities and their functional characteristics in the riparian zone. Plant functional traits which reflect the physiological and ecological processes of plants in particular ecosystems are crucial for indicating the variations in the ecosystem structure and function. To better understand the adaptation strategies of plants to hydrological changes and provide a scientific basis for the selection of species in the re-vegetation of the newly formed ecosystems, 14 leaf functional traits and leaf economics spectrum (LES) of 19 dominant plants under different hydrological conditions were investigated in the water level fluctuation zone (WLFZ) of the Three Gorges Reservoir (TGR). The results showed that anti-seasonal flooding has significant effects on the leaf functional traits of plants (P < 0.05). The net photosynthetic rate of annual plants was significantly higher than that of perennial plants (P < 0.05), and there was a significant correlation between leaf phenotypic and photosynthetic traits (P < 0.05). Canonical correspondence analysis showed that soil water content and available phosphorus were the main factors affecting the leaf function of dominant species, indicating that hydrologic factors were still important environmental factors affecting leaf functional traits of dominant species in the WLFZ. And annuals from the WLFZ have characteristics of thick leaves, high photosynthetic rate, short lifespan, and high nutrient concentrations, which make them close to the fast investment-return end of LES. On the contrary, perennials are close to the slow investment-return end of LES. The high productivity investment of annuals is better than the high defense investment of perennials for adapting to the special habitats in the WLFZ. These results indicated that different functional plants in the WLFZ of the TGR under different hydrological regimes can adopt different strategies by weighing the associations and trade-offs between their economic traits.

Clinical Features and Outcomes of Pulmonary Artery Sarcoma.

OBJECTIVES: A retrospective cohort study was designed to describe the clinical features and outcomes of pulmonary artery sarcoma (PAS). METHODS: Twenty-two (22) consecutive patients diagnosed with PAS by pathological examination were enrolled and followed up until they died or until January 2020. The medical records were retrospectively reviewed to evaluate the clinical characteristics, image findings, and outcomes. RESULTS: 1) Twenty-one (21, 95.5%) patients were firstly misdiagnosed. Dyspnoea was the most common presenting symptom (19 of 22, 86.4%). 2) Filling defects in the right pulmonary artery were seen in 17 patients (77.3%) with computed tomography pulmonary angiography or magnetic resonance pulmonary angiography. Among those patients, 14 underwent positron emission tomography-computed tomography detection and 13 (92.9%) were found to have increased uptake value in the pulmonary artery. 3) The median survival (from diagnosis to death or January 2020) of the total series was 11.6 months (range, 0.7-68.5 months). The estimated cumulative survival rates at 1, 2, and 3 years were 52.6%, 32.8%, and 19.7%, respectively. Patients who received surgery and/or chemo-radiotherapy treatment had a better survival rate compared with patients without treatment (the estimated cumulative survival rates at 1, 2, and 3 years were 60.3%, 39.1%, and 29.3%, respectively, vs 33.3%, 16.6%, and 0, accordingly) and better survival time (median survival 17.02 vs 3.16 months, respectively) (p=0.025). CONCLUSIONS: Pulmonary artery sarcoma is easily misdiagnosed, as the symptoms and routine image detection are nonspecific. Positron emission tomography-computed tomography may be helpful in diagnosis. Surgery and/or chemo-radiotherapy offer a chance for better outcomes.

Imaging of cardiac fibroblast activation in patients with chronic thromboembolic pulmonary hypertension.

PURPOSE: The aim of this study was to explore the association of cardiac fibroblast activation with clinical parameters and cardiovascular magnetic resonance (CMR) imaging parameters in patients with chronic thromboembolic pulmonary hypertension (CTEPH). METHODS: Thirteen CTEPH patients were prospectively enrolled. All of the patients underwent cardiac 68Gallium-labelled fibroblast activation protein inhibitor (68 Ga-FAPI-04)-positron emission tomography/computed tomography (PET/CT), right heart catheterisation, and echocardiography, and 11 of them additionally underwent CMR. Thirteen control subjects were selected to establish the normal range of cardiac 68 Ga-FAPI-04 uptake. Cardiac 68 Ga-FAPI-04 uptake higher than that in the blood pool was defined as abnormal. The global and segmental maximum standardised uptake values (SUVmax) of the right ventricle (RV) were measured and further expressed as target-to-background ratio (TBRRV) with left ventricular lateral wall activity as background. Late gadolinium enhancement (LGE) was visually evaluated, and native-T1 times, enhanced-T1 times, and extracellular volume (ECV) were quantitatively measured. RESULTS: Ten CTEPH patients (77%) had abnormal 68 Ga-FAPI-04 uptake in RV, mainly located in the free wall, which was significantly higher than that in controls (TBRRV: 2.4 ± 0.9 vs 1.0 ± 0.1, P < 0.001). The TBRRV correlated positively with the thickness of RV wall (r = 0.815, P = 0.001) and inversely with RV fraction area change (RVFAC) (r = - 0.804, P = 0.001) and tricuspid annular plane systolic excursion (TAPSE) (r = - 0.678, P = 0.011). No correlation was found between 68 Ga-FAPI-04 activity and CMR imaging parameters. CONCLUSION: Fibroblast activation in CTEPH, measured by 68 Ga-FAPI-04 imaging, is mainly localised in the RV free wall. Enhanced fibroblast activation reflects the thickening of the RV wall and decreased RV contractile function.

PRRX1 Loss-of-Function Mutations Underlying Familial Atrial Fibrillation.

Background Atrial fibrillation (AF) is the most common form of clinical cardiac dysrhythmia responsible for thromboembolic cerebral stroke, congestive heart failure, and death. Aggregating evidence highlights the strong genetic basis of AF. Nevertheless, AF is of pronounced genetic heterogeneity, and in an overwhelming majority of patients, the genetic determinants underpinning AF remain elusive. Methods and Results By genome-wide screening with polymorphic microsatellite markers and linkage analysis in a 4-generation Chinese family affected with autosomal-dominant AF, a novel locus for AF was mapped to chromosome 1q24.2-q25.1, a 3.20-cM (≈4.19 Mbp) interval between markers D1S2851 and D1S218, with the greatest 2-point logarithm of odds score of 4.8165 for the marker D1S452 at recombination fraction=0.00. Whole-exome sequencing and bioinformatics analyses showed that within the mapping region, only the mutation in the paired related homeobox 1 (PRRX1) gene, NM_022716.4:c.319C>T;(p.Gln107*), cosegregated with AF in the family. In addition, sequencing analyses of PRRX1 in another cohort of 225 unrelated patients with AF revealed a new mutation, NM_022716.4:c.437G>T; (p.Arg146Ile), in a patient. The 2 mutations were absent in 908 control subjects. Biological analyses in HeLa cells demonstrated that the 2 mutants had significantly diminished transactivation on the target genes ISL1 and SHOX2 and markedly decreased ability to bind the promoters of ISL1 and SHOX2 (2 genes causally linked to AF), although with normal intracellular distribution. Conclusions This study first indicates that PRRX1 loss-of-function mutations predispose to AF, which provides novel insight into the molecular pathogenesis underpinning AF, implying potential implications for precisive prophylaxis and management of AF.

Sclerotinia Stem Rot Resistance in Rapeseed: Recent Progress and Future Prospects.

Sclerotinia stem rot (SSR) of rapeseed (Brassica napus), caused by the soil-borne fungus Sclerotinia sclerotiorum, is one of the main diseases seriously affecting the yield and oil quality of infected rapeseed crops. The complexity of the inheritance of resistance and of the interaction mechanisms between rapeseed and S. sclerotiorum limits resistance gene identification and molecular breeding. In this review, the latest progress of research into resistance to SSR in B. napus is summarized from the following three directions: the pathogenesis mechanisms of S. sclerotiorum, the resistance mechanisms of B. napus toward S. sclerotiorum, and rapeseed breeding for resistance to SSR. This review aims to provide a theoretical basis and useful reference for analyzing the mechanism of the interaction between B. napus and S. sclerotiorum, searching for gene loci associated with the resistance response, and for achieving disease-resistance genetic manipulation and molecular design breeding in rapeseed.

Value of 18F-fluorodeoxyglucose positron emission tomography/computed tomography in the evaluation of pulmonary artery activity in patients with Takayasu's arteritis.

AIMS: To explore the value of 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) in the detection of active pulmonary artery (PA) lesions in patients with Takayasu's arteritis (TA). METHODS AND RESULTS: Consecutive TA patients with PA involvement were prospectively recruited. Clinical activity was assessed according to the National Institutes of Health (NIH) criteria. CT pulmonary angiography (CTPA) or magnetic resonance pulmonary angiography was performed for evaluation of vascular structural characteristics, and mural thickening was considered as radiologically active. A vascular segment with 18F-FDG uptake ≥ liver was considered as PET-active. A total of 38 18F-FDG PET/CT scans were performed in 29 patients. In terms of disease activity, the sensitivity of 18F-FDG PET/CT did not significantly differ from radiological imaging (71.4% vs. 92.9%, P = 0.250), but 18F-FDG PET/CT had higher specificity (91.7% vs. 37.5%, P = 0.001) and accuracy (84.2% vs. 57.9%, P = 0.022). Although the majority of PET-active PA segments (54.9%) showed mural thickening, 14 PA segments with normal structure were also PET-active. 18F-FDG activity did not significantly differ between the PA and aorta in clinically active patients. In addition, 18F-FDG activity of the PA was positively correlated with inflammatory markers. Changes in 18F-FDG activity in PA during follow-up reflected therapeutic effects. CONCLUSION: 18F-FDG PET/CT can effectively evaluate PA activity in TA patients, and its diagnostic performance is superior to radiological imaging. The 18F-FDG activity of PA shows a good correlation with clinical disease status and inflammatory markers and can be used to monitor therapeutic effects.

ISL1 loss-of-function variation causes familial atrial fibrillation.

Atrial fibrillation (AF) represents the most frequent form of sustained cardiac rhythm disturbance, affecting approximately 1% of the general population worldwide, and confers a substantially enhanced risk of cerebral stroke, heart failure, and death. Increasing epidemiological studies have clearly demonstrated a strong genetic basis for AF, and variants in a wide range of genes, including those coding for ion channels, gap junction channels, cardiac structural proteins and transcription factors, have been identified to underlie AF. Nevertheless, the genetic pathogenesis of AF is complex and still far from completely understood. Here, whole-exome sequencing and bioinformatics analyses of a three-generation family with AF were performed, and after filtering variants by multiple metrics, we identified a heterozygous variant in the ISL1 gene (encoding a transcription factor critical for embryonic cardiogenesis and postnatal cardiac remodeling), NM_002202.2: c.481G > T; p.(Glu161*), which was validated by Sanger sequencing and segregated with autosome-dominant AF in the family with complete penetrance. The nonsense variant was absent from 284 unrelated healthy individuals used as controls. Functional assays with a dual-luciferase reporter assay system revealed that the truncating ISL1 protein lost transcriptional activation on the verified target genes MEF2C and NKX2-5. Additionally, the variant nullified the synergistic transactivation between ISL1 and TBX5 as well as GATA4, two other transcription factors that have been implicated in AF. The findings suggest ISL1 as a novel gene contributing to AF, which adds new insight to the genetic mechanisms underpinning AF, implying potential implications for genetic testing and risk stratification of the AF family members.

A New TBX5 Loss-of-Function Mutation Contributes to Congenital Heart Defect and Atrioventricular Block.

Congenital heart defect (CHD) represents the most common birth deformity, afflicting 1% of all births worldwide, and accounts for substantial morbidity and mortality. Increasing evidence highlights the pivotal roles of genetic etiologies in the pathogenesis of CHD, and pathogenic mutations in multiple genes, including TBX5 encoding a cardiac core transcription factor key to cardiovascular morphogenesis, have been involved in CHD. However, due to pronounced genetic heterogeneity of CHD, the genetic determinants underlying CHD in most cases remain obscure. In this investigation, by sequencing analysis of the coding exons and flanking introns of the TBX5 gene in 198 unrelated patients affected with CHD, a novel heterozygous mutation, NM_000192.3: c.692C>T; p. (Pro231Leu), was identified in an index patient with familial double outlet right ventricle (DORV), ventricular septal defect (VSD), and atrioventricular block (AVB). Genetic analysis of the proband's pedigree showed that the mutation co-segregated with the diseases. The missense mutation, which altered the amino acid conserved evolutionarily, was absent from 266 unrelated healthy subjects. Functional analyses with a dual-luciferase reporter assay system unveiled that the Pro231Leu-mutant TBX5 was associated with significantly reduced transcriptional activity on its target genes MYH6 and NPPA. Furthermore, the mutation disrupted the synergistic transactivation between TBX5 and NKX2-5 as well as GATA4, two other transcription factors causally linked to CHD. This study firstly links TBX5 loss-of-function mutation to familial DORV, VSD, and AVB, which provides novel insight into the mechanism underpinning CHD and AVB, suggesting potential implications for genetic evaluation and individualized treatment of patients affected by CHD and AVB.

Lowering effects of fish oil supplementation on proinflammatory markers in hypertension: results from a randomized controlled trial.

Reduced inflammation is one of the potential mechanisms underlying the cardioprotective efficacy of fish oil enriched with eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Supplementation with fish oil has favorable effects on cardiometabolic profiles in Inner Mongolia patients with hypertension, but whether the cardiovascular benefits can be ascribed to reduced subclinical inflammation is unclear among this population. Seventy-seven middle-aged/elderly hypertensive volunteers were randomly assigned to receive either fish oil (FO, n = 38, 2 g day-1 EPA + DHA) or control corn oil (CO, n = 39) for 90 days. FA compositions in erythrocytes and C-reactive protein (CRP, mg L-1), interleukin-6 (IL-6, pg mL-1) and tumor necrosis factor-α (TNF-α, pg mL-1) concentrations in the plasma were measured before and after the 90-day supplementation, and the cardiometabolic risk was expressed as continuously distributed z-scores calculated by standardizing and then summing the individual cardiovascular risk factors. Significant reductions in the TNF-α (-1.87 ± 2.71 vs. -0.64 ± 2.62, p = 0.02) and CRP levels (-0.85 ± 2.49 vs. 0.56 ± 2.14, p = 0.01) were found in the FO group compared with the CO group, but not in the IL-6 levels (-0.66 ± 1.05 vs. -0.25 ± 0.94, p = 0.10). The decreases in the changes of TNF-α levels were positively correlated with the reductions in the cardiometabolic risk scores in the subjects supplemented with FO (r = 0.35, p = 0.02), but not in the control subjects supplemented with CO (r = 0.09, p = 0.54). FO supplementation increased the levels of EPA (p = 0.013), DHA (p = 0.040) and total n-3 FA (p = 0.035), and decreased the levels of 20:4n-6 (p = 0.041) and total n-6 FA (p = 0.011) and the ratio of n-6 to n-3 FA (p = 0.001), compared with the changes related to the CO group. The increases in the changes of erythrocyte total n-3 FA levels were inversely correlated with the concentrations of TNF-α (r = -0.34, p = 0.001) and CRP (r = -0.29, p = 0.020). The present findings suggest that fish oil supplementation may attenuate the proinflammatory reactions in hypertension, which might help promote the cardiometabolic benefits in this Inner Mongolia population.

Arabidopsis GDSL1 overexpression enhances rapeseed Sclerotinia sclerotiorum resistance and the functional identification of its homolog in Brassica napus.

Sclerotinia stem rot (SSR) caused by Sclerotinia sclerotiorum is a devastating disease of rapeseed (Brassica napus L.). To date, the genetic mechanisms of rapeseed' interactions with S. sclerotiorum are not fully understood, and molecular-based breeding is still the most effective control strategy for this disease. Here, Arabidopsis thaliana GDSL1 was characterized as an extracellular GDSL lipase gene functioning in Sclerotinia resistance. Loss of AtGDSL1 function resulted in enhanced susceptibility to S. sclerotiorum. Conversely, overexpression of AtGDSL1 in B. napus enhanced resistance, which was associated with increased reactive oxygen species (ROS) and salicylic acid (SA) levels, and reduced jasmonic acid levels. In addition, AtGDSL1 can cause an increase in lipid precursor phosphatidic acid levels, which may lead to the activation of downstream ROS/SA defence-related pathways. However, the rapeseed BnGDSL1 with highest sequence similarity to AtGDSL1 had no effect on SSR resistance. A candidate gene association study revealed that only one AtGDSL1 homolog from rapeseed, BnaC07g35650D (BnGLIP1), significantly contributed to resistance traits in a natural B. napus population, and the resistance function was also confirmed by a transient expression assay in tobacco leaves. Moreover, genomic analyses revealed that BnGLIP1 locus was embedded in a selected region associated with SSR resistance during the breeding process, and its elite allele type belonged to a minor allele in the population. Thus, BnGLIP1 is the functional equivalent of AtGDSL1 and has a broad application in rapeseed S. sclerotiorum-resistance breeding.

Correction to: Multiple cardiovascular involvements in Behçet's disease: unique utility of 18F-FDG PET/CT in diagnosis and follow-up.

Figure c of the original version of this article was not converted properly. Correct figure is presented here. The original article has been corrected.

Effects of n-3 fatty acid supplements on cardiometabolic profiles in hypertensive patients with abdominal obesity in Inner Mongolia: a randomized controlled trial.

Daily supplementation with n-3 fatty acid (FA) has been believed to be an adjunct or alternative to drug treatments to reduce blood pressure (BP) and triglyceride (TG) levels in western patients with high risk of cardiovascular disease. The BP-lowering effect of n-3 FA supplements among Chinese hypertensive patients has been reported in our previous 12-week, double-blind, randomized controlled trial (RCT), but the benefits on cardiometabolic profiles among obese Chinese populations are not well known. We therefore used the data from the previous RCT to investigate the effects of marine- and plant-derived n-3 FA supplements on cardiometabolic profiles in middle-aged and elderly Chinese hypertensive patients with abdominal obesity. In total, 108 eligible volunteers from Inner Mongolia, China were randomly assigned to three treatments for 12 weeks: fish oil (FO, n = 35, 2 g day-1 eicosapentaenoic acid + docosahexaenoic acid), flaxseed oil (FLO, n = 39, 2.5 g day-1 α-linolenic acid), and corn oil served as a control (CO, n = 34). BP, blood lipids, waist circumference (WC) and fasting glucose-insulin were measured at baseline and after 12-week intervention by using standard methods. Clustered cardiometabolic risk was expressed as a continuously distributed z-score calculated by standardizing and then summing WC, insulin, glucose, TG, HDL-cholesterol and BP values. The cardiometabolic risk scores were significantly lower in the FO group than in the CO group after the 12-week intervention (-0.41 ± 0.92 vs. 0.02 ± 0.95, p = 0.016), but not in the FLO group (-0.23 ± 1.02 vs. 0.02 ± 0.95, p = 0.109). For individual risk factors, compared with CO, FO significantly decreased LDL-cholesterol (-0.25 ± 0.78 mmol L-1vs. -0.05 ± 0.65 mmol L-1, p = 0.010), ApoB (-012 ± 0.28 mmol L-1vs. -0.03 ± 0.23 mmol L-1, p = 0.036), and WC (-1.58 ± 3.67 cm vs. -0.52 ± 3.27 cm, p = 0.031), whereas no significant difference was found between FLO and CO groups in LDL-cholesterol (p = 0.081), ApoB (p = 0.102) and WC (p = 0.093). The present findings suggest that marine n-3 FA intervention may improve the cardiometabolic traits in this Chinese hypertensive population comorbid with abdominal obesity.

Value of 18F-FDG PET/CT in differentiating malignancy of pulmonary artery from pulmonary thromboembolism: a cohort study and literature review.

To determine the value of 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) in differentiating malignancy of pulmonary artery (PA) from pulmonary thromboembolism (PTE) based on a larger number of cases by pooling our cases and those from the literature. Consecutive patients with a PA lesion who had undergone 18F-FDG PET/CT in our hospital were retrospectively reviewed. Moreover, PubMed, Embase, and Medline were searched for literature reporting individual maximum standardised uptake value (SUVmax) of the malignant PA lesion and/or PTE. 18F-FDG activity was compared between PA malignancy and PTE by pooling the data from literature and our patients. Receiver operating characteristic curve analysis was performed to determine the ability of SUVmax to differentiate PA malignancy from PTE. From our database, we identified 11 patients with pulmonary artery sarcoma (PAS), and nine cases of PTE. Fifty patients with a malignant PA lesion (40 cases of PAS and 10 cases of tumor embolism) and 22 subjects with PTE were extracted from the literature. In our cases, the SUVmax of PAS (11.1 ± 4.9, range: 5.5-19.9) was significantly higher than that of PTE (1.9 ± 0.6, range: 1.1-3.2; P < 0.001). There was no significant difference in the SUVmax between the literature data and our cases in malignant lesions or in PTE. Based on the pooled analysis of the literature data and our cases (61 cases of malignant lesions and 31 cases of PTE), the area under the curve for SUVmax to differentiate PA malignancy from PTE was 0.996 (95% CI: 0.989-1.000). At a cutoff value of 3.3, the sensitivity, specificity, and accuracy were 98.4%, 96.8%, and 97.8%, respectively. The 18F-FDG uptake value is an accurate index for determining PA malignancy.

Identification and Functional Characterization of an ISL1 Mutation Predisposing to Dilated Cardiomyopathy.

Dilated cardiomyopathy (DCM) is the most prevalent cause of non-ischemic cardiac failure and the commonest indication for cardiac transplantation. Compelling evidence highlights the pivotal roles of genetic defects in the occurrence of DCM. Nevertheless, the genetic determinants underpinning DCM remain largely obscure. In this study, the coding regions of ISL1, which encodes a transcription factor critical for embryonic cardiogenesis and postnatal cardiac remodeling, were sequenced in 216 unrelated patients with DCM, and a novel heterozygous ISL1 mutation, NM_002202.2: c.631A>T; p.(Lys211*), was identified in a proband. The mutation, which co-segregated with DCM in the family, was absent in 238 unrelated controls, as well as in the Genome Aggregation and the Exome Aggregation Consortium population databases. Functional analyses unveiled that the mutant ISL1 protein lost transcriptional activity alone or in synergy with TBX20 or GATA4, two other transcription factors associated with DCM. These findings indicate ISL1 as a new gene of DCM.