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1.
Sci Data ; 11(1): 725, 2024 Jul 02.
Article in English | MEDLINE | ID: mdl-38956385

ABSTRACT

Teratoma, due to its remarkable ability to differentiate into multiple cell lineages, is a valuable model for studying human embryonic development. The similarity of the gene expression and chromatin accessibility patterns in these cells to those observed in vivo further underscores its potential as a research tool. Notably, teratomas derived from human naïve (pre-implantation epiblast-like) pluripotent stem cells (PSCs) have larger embryonic cell diversity and contain extraembryonic lineages, making them more suitable to study developmental processes. However, the cell type-specific epigenetic profiles of naïve PSC teratomas have not been yet characterized. Using single-cell assay for transposase-accessible chromatin sequencing (scATAC-seq), we analyzed 66,384 cell profiles from five teratomas derived from human naïve PSCs and their post-implantation epiblast-like (primed) counterparts. We observed 17 distinct cell types from both embryonic and extraembryonic lineages, resembling the corresponding cell types in human fetal tissues. Additionally, we identified key transcription factors specific to different cell types. Our dataset provides a resource for investigating gene regulatory programs in a relevant model of human embryonic development.


Subject(s)
Chromatin , Pluripotent Stem Cells , Single-Cell Analysis , Teratoma , Humans , Teratoma/genetics , Teratoma/pathology , Pluripotent Stem Cells/metabolism , Cell Lineage , Transcription Factors/genetics
2.
Heart Rhythm ; 2024 Jun 18.
Article in English | MEDLINE | ID: mdl-38901520

ABSTRACT

BACKGROUND: The association between serum potassium and atrial fibrillation (AF) recurrence after catheter ablation remains unclear. OBJECTIVE: To investigate whether preprocedural serum potassium influences AF recurrence in patients underwent catheter ablation. METHODS: We used data of AF patients who underwent de novo catheter ablation from the prospective Chinese Atrial Fibrillation Registry Study (CAFR). Patients with prior ablation and without baseline serum potassium were excluded. The primary outcome was 1-year AF recurrence after 3-month blanking period from the ablation. Restricted cubic spline and Cox proportional models were used to compare outcomes across serum potassium categories. RESULTS: A total of 4838 AF patients with de novo catheter ablation was enrolled. At 1 year, AF recurrence occurred in 1347 (27.8%) patients. The relationship between preprocedural serum potassium and 1-year AF recurrence after ablation presented as U-shape (P for nonlinear = 0.048). Compared with the group of serum potassium within 4.41-4.60 mmol/L, the risk of AF recurrence increased significantly in the lowest serum potassium group (≤4.00 mmol/L) after multivariate analysis (HR 1.26, 95% CI 1.06-1.51, P = 0.010). Other categories with lower or higher serum potassium levels including 4.01-4.20 mmol/L (HR=1.18), 4.21-4.40 mmol/L (HR=1.16), 4.61-4.80 mmol/L (HR=1.07) and ≥4.81 mmol/L (HR=1.11) showed nonsignificant higher recurrence risk. CONCLUSIONS: The relationship between preprocedural potassium and AF recurrence was U-shaped, with an optimal potassium range (4.41-4.60 mmol/L). Lower potassium level is associated with increased AF recurrence risk after catheter ablation.

3.
Circ Arrhythm Electrophysiol ; 17(5): e012513, 2024 May.
Article in English | MEDLINE | ID: mdl-38690657

ABSTRACT

BACKGROUND: The anatomy of myocardial fibers around the right cardiac veins (RCVs) and their roles in accessory pathways (APs) are rarely reported. METHODS: Six RCV-APs were identified from 566 patients with right-sided APs. Mapping of retrograde atrial activation was performed using CARTO 3 system under orthodromic tachycardia or right ventricular pacing. Venography of RCVs was acquired at the earliest retrograde atrial activation. RESULTS: Patients enrolled had a median age of 30 (11-51) years, 5 of them were male. Venography of RCVs could be classified into 3 distinct patterns based on the identified ventricular branches, right marginal vein only (type I; n=3), both right marginal vein and anterior cardiac veins (type II; n=2), and anterior cardiac vein only (type III; n=1). Patients with type I venography had rS QRS pattern in lead V1, negative delta wave in lead III and negative or isoelectric delta wave in lead aVF. However, patients with type II and III venography had QS QRS patterns in lead V1 and variable patterns of delta wave in inferior leads. Earliest retrograde atrial activation was found at a median of 16.75 (14.60-20.00) mm away from the tricuspid annulus, all with A larger than V. At the earliest retrograde atrial activation, far-field ventricular electrogram was found 30 ms later than QRS onset in 1 patient under sinus rhythm. AP conduction was eliminated by mechanical pressure in 2 and by radiofrequency ablation in 4 at the ostium of the veins colocalizing with the earliest retrograde activation of the right atrium. No recurrence was observed during 36 (10-60) months follow-up. CONCLUSIONS: The RCV-AP is a rare form of right-sided APs characterized by atrial insertions distant from the annulus. ECG-speculated ventricular insertion sites conformed to the location of identified RCVs.


Subject(s)
Accessory Atrioventricular Bundle , Catheter Ablation , Phlebography , Humans , Male , Adult , Female , Middle Aged , Accessory Atrioventricular Bundle/physiopathology , Accessory Atrioventricular Bundle/surgery , Adolescent , Young Adult , Child , Electrophysiologic Techniques, Cardiac , Coronary Vessels/physiopathology , Coronary Vessels/diagnostic imaging , Action Potentials , Heart Rate , Cardiac Pacing, Artificial
4.
J Am Coll Cardiol ; 83(20): 1957-1969, 2024 May 21.
Article in English | MEDLINE | ID: mdl-38749614

ABSTRACT

BACKGROUND: It is still unclear whether small left ventricle (LV) is an adverse structural prognostic feature in patients with atrial fibrillation (AF). OBJECTIVES: The purpose of this study was to evaluate the association between small LV and risk of cardiovascular events in AF population. METHODS: From the China-AF registry, 7,764 patients with AF were enrolled and divided into groups with normal, small, and large LV size based on left ventricular end-diastolic dimension (LVEDD) measurement per the American Society of Echocardiography references. Cox models were used to assess the association between LV size or LVEDD with composite cardiovascular events (cardiovascular death, ischemic stroke or systemic embolism, or major bleeding). RESULTS: There were 308 (4.0%) participants assessed with small LV who were older, with lower body mass and blood pressure, and fewer comorbidities, and 429 (5.5%) were identified with large LV. Compared with the normal LV group, small LV and large LV were significantly associated with higher incidence of composite cardiovascular events (adjusted HR [aHR]: 1.54 [95% CI: 1.07-2.20] for small LV; aHR: 1.36 [95% CI: 1.02-1.81] for large LV) and cardiovascular death (aHR: 1.94 [95% CI: 1.14-3.28] for small LV; aHR: 1.83 [95% CI: 1.24-2.69] for large LV). Small LV was also associated with increased risk of major bleeding [aHR: 2.21 [95% CI: 1.01-4.86]). A U-shaped relationship between LVEDD and composite cardiovascular events was identified (Pnonlinear < 0.001). CONCLUSIONS: In a prospective AF cohort, small LV was independently associated with an increased risk of cardiovascular events, which needed consideration in risk stratification and management for patients with AF. (ChiCTR-OCH-13003729).


Subject(s)
Atrial Fibrillation , Heart Ventricles , Aged , Female , Humans , Male , Middle Aged , Atrial Fibrillation/epidemiology , Atrial Fibrillation/complications , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/etiology , China/epidemiology , Echocardiography , Heart Ventricles/diagnostic imaging , Heart Ventricles/physiopathology , Organ Size , Prospective Studies , Registries , Risk Assessment/methods , Risk Factors
5.
Nature ; 629(8010): 154-164, 2024 May.
Article in English | MEDLINE | ID: mdl-38649488

ABSTRACT

Muscle atrophy and functional decline (sarcopenia) are common manifestations of frailty and are critical contributors to morbidity and mortality in older people1. Deciphering the molecular mechanisms underlying sarcopenia has major implications for understanding human ageing2. Yet, progress has been slow, partly due to the difficulties of characterizing skeletal muscle niche heterogeneity (whereby myofibres are the most abundant) and obtaining well-characterized human samples3,4. Here we generate a single-cell/single-nucleus transcriptomic and chromatin accessibility map of human limb skeletal muscles encompassing over 387,000 cells/nuclei from individuals aged 15 to 99 years with distinct fitness and frailty levels. We describe how cell populations change during ageing, including the emergence of new populations in older people, and the cell-specific and multicellular network features (at the transcriptomic and epigenetic levels) associated with these changes. On the basis of cross-comparison with genetic data, we also identify key elements of chromatin architecture that mark susceptibility to sarcopenia. Our study provides a basis for identifying targets in the skeletal muscle that are amenable to medical, pharmacological and lifestyle interventions in late life.


Subject(s)
Aging , Muscle, Skeletal , Single-Cell Analysis , Adolescent , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Young Adult , Aging/genetics , Aging/pathology , Aging/physiology , Cell Nucleus/metabolism , Chromatin/metabolism , Chromatin/genetics , Disease Susceptibility , Epigenesis, Genetic , Frailty/genetics , Frailty/pathology , Muscle, Skeletal/cytology , Muscle, Skeletal/metabolism , Muscle, Skeletal/pathology , Muscular Atrophy/genetics , Muscular Atrophy/pathology , Sarcopenia/genetics , Sarcopenia/pathology , Transcriptome
6.
JACC Clin Electrophysiol ; 10(4): 685-694, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38658060

ABSTRACT

BACKGROUND: Reconnection after mitral isthmus (MI) block with radiofrequency ablation is common. OBJECTIVES: The aim of this study was to investigate the effects of ethanol infusion in the vein of Marshall (EIVOM) on acute reconnection after MI bidirectional block. METHODS: Patients with persistent atrial fibrillation who were scheduled to receive radiofrequency ablation for the first time were randomly assigned to the radiofrequency catheter ablation (RFCA) group (n = 44) or the EIVOM group (n = 45). The RFCA group's strategy was bilateral pulmonary vein ablation and linear ablation; in the EIVOM group, EIVOM was performed first. The primary endpoint was acute reconnection 30 minutes after MI bidirectional block. RESULTS: A total of 89 patients (average age 62.9 years; 57.3% male) were enrolled. The average duration for persistent atrial fibrillation was 2.3 years. Before observation, all patients in the EIVOM group achieved MI bidirectional block (45 of 45 [100%]), compared with 84.1% (37 of 44) in the RFCA group. After the observation, 3 cases of MI reconnection occurred in the EIVOM group and 13 cases in the RFCA group (6.7% vs 35.1%; P < 0.05). After additional ablation, the final MI block rates in the EIVOM and RFCA groups were 97.8% (44 of 45) and 72.7% (32 of 44), respectively. During a 1-year follow-up, 8 of 45 patients who underwent EIVOM had recurrent atrial fibrillation, compared with 14 of 44 in the RFCA group (17.8% vs 31.8%; P < 0.01). CONCLUSIONS: EIVOM can reduce acute reconnection after MI bidirectional block and significantly increase first-pass MI block.


Subject(s)
Atrial Fibrillation , Catheter Ablation , Mitral Valve , Pulmonary Veins , Humans , Male , Female , Middle Aged , Atrial Fibrillation/surgery , Catheter Ablation/methods , Aged , Mitral Valve/surgery , Pulmonary Veins/surgery , Ethanol/administration & dosage , Recurrence , Treatment Outcome
7.
Nat Genet ; 56(5): 938-952, 2024 May.
Article in English | MEDLINE | ID: mdl-38627596

ABSTRACT

Cholestatic liver injuries, characterized by regional damage around the bile ductular region, lack curative therapies and cause considerable mortality. Here we generated a high-definition spatiotemporal atlas of gene expression during cholestatic injury and repair in mice by integrating spatial enhanced resolution omics sequencing and single-cell transcriptomics. Spatiotemporal analyses revealed a key role of cholangiocyte-driven signaling correlating with the periportal damage-repair response. Cholangiocytes express genes related to recruitment and differentiation of lipid-associated macrophages, which generate feedback signals enhancing ductular reaction. Moreover, cholangiocytes express high TGFß in association with the conversion of liver progenitor-like cells into cholangiocytes during injury and the dampened proliferation of periportal hepatocytes during recovery. Notably, Atoh8 restricts hepatocyte proliferation during 3,5-diethoxycarbonyl-1,4-dihydro-collidin damage and is quickly downregulated after injury withdrawal, allowing hepatocytes to respond to growth signals. Our findings lay a keystone for in-depth studies of cellular dynamics and molecular mechanisms of cholestatic injuries, which may further develop into therapies for cholangiopathies.


Subject(s)
Cholestasis , Hepatocytes , Animals , Mice , Cholestasis/genetics , Cholestasis/pathology , Cholestasis/metabolism , Hepatocytes/metabolism , Liver/metabolism , Liver/injuries , Liver/pathology , Cell Proliferation/genetics , Bile Ducts/metabolism , Liver Regeneration/genetics , Mice, Inbred C57BL , Basic Helix-Loop-Helix Transcription Factors/genetics , Basic Helix-Loop-Helix Transcription Factors/metabolism , Signal Transduction , Male , Transforming Growth Factor beta/metabolism , Transforming Growth Factor beta/genetics , Transcriptome , Disease Models, Animal , Spatio-Temporal Analysis
8.
Clin Cardiol ; 47(2): e24233, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38375935

ABSTRACT

BACKGROUND: There is great heterogeneity in the quality of care among hospitals in China, but studies on the performance measures and prognosis of patients with heart failure (HF) are still deficient. HYPOTHESIS: Performance measures have been used as a guideline to clinicans, however, the association between them and outcomes among HF patients in China remains unclear. METHODS: We analyzed 4497 patients with HF from the Heart Failure Registry of Patient Outcomes study. Performance measures were determined according to the guidelines, and the patients were divided into four groups based on a composite performance score. Multiple imputation and Cox proportional-hazard regression models were used to assess the association between the performance measures and clinical outcomes. RESULTS: Overall, only 12.5% of patients met the top 25% of the performance measures, whereas 33.5% of patients met the bottom 25% of the measures. A total of 992 (22.2%) patients died within 1 year, involving a larger proportion of patients who had met only the bottom 25% of the performance measures than had met the top 25% (27.0% vs. 16.3%, respectively). The patients who met the top 25% of the measures had a lower 1-year mortality rate (adjusted hazard ratio: 0.78, 95% confidence interval: 0.61-0.98). CONCLUSIONS: The association between performance measures and mortality appeared to follow a dose-response pattern with a larger degree of compliance with performance measures being associated with a lower mortality rate in patients with HF. Accordingly, the quality of care for patients with HF in China needs to be further improved.


Subject(s)
Guideline Adherence , Heart Failure , Humans , Hospitals , Heart Failure/diagnosis , Heart Failure/epidemiology , Heart Failure/therapy , Proportional Hazards Models , China/epidemiology , Registries
9.
Nat Commun ; 15(1): 583, 2024 Jan 17.
Article in English | MEDLINE | ID: mdl-38233381

ABSTRACT

In contrast to rodents, the mechanisms underlying human trophectoderm and early placenta specification are understudied due to ethical barriers and the scarcity of embryos. Recent reports have shown that human pluripotent stem cells (PSCs) can differentiate into trophectoderm (TE)-like cells (TELCs) and trophoblast stem cells (TSCs), offering a valuable in vitro model to study early placenta specification. Here, we demonstrate that the VGLL1 (vestigial-like family member 1), which is highly expressed during human and non-human primate TE specification in vivo but is negligibly expressed in mouse, is a critical regulator of cell fate determination and self-renewal in human TELCs and TSCs derived from naïve PSCs. Mechanistically, VGLL1 partners with the transcription factor TEAD4 (TEA domain transcription factor 4) to regulate chromatin accessibility at target gene loci through histone acetylation and acts in cooperation with GATA3 and TFAP2C. Our work is relevant to understand primate early embryogenesis and how it differs from other mammalian species.


Subject(s)
Pluripotent Stem Cells , Transcription Factors , Pregnancy , Female , Humans , Mice , Animals , Cell Lineage/genetics , Transcription Factors/genetics , Trophoblasts/physiology , Cell Differentiation/genetics , Mammals , Primates , DNA-Binding Proteins/genetics , TEA Domain Transcription Factors
10.
Pacing Clin Electrophysiol ; 47(1): 58-65, 2024 01.
Article in English | MEDLINE | ID: mdl-38010824

ABSTRACT

BACKGROUND: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) is reported to reduce incident atrial fibrillation (AF) in patients with or without diabetes; however, its cardiovascular (CV) benefit for AF patients remains unclear. SS AIMS: To investigate the effect of SGLT2i on the incidence of CV events in patients with AF. METHODS: Six randomized controlled trials (RCTs) assessing the effects of SGLT2i on CV outcomes in patients with or without AF were included (PROSPERO: CRD 42023431535). The primary endpoint was the composite outcome of heart failure (HF) hospitalization and CV death. Additionally, we assessed the effects of treatment in prespecified subgroups on HF hospitalization, CV death, and all-cause mortality. RESULTS: Among 38,529 participants from all trials, 5018 patients with AF were treated with SGLT2i. The follow-up period of these trials ranged from 2.3 to 3.3 years. SGLT2i treatment was significantly associated with the risk reduction of primary endpoint in patients with AF (risk ratio [RR] 0.81, 95% confidence interval [CI] 0.74-0.88; p < 0.001), consistent with the finding in the general population (p for interaction = 0.76). SGLT2i was also associated with a consistent reduction in the risk of HF hospitalization in patients with AF (RR 0.76, 95% CI 0.69-0.84; p < 0.001) or not (RR 0.72, 95% CI 0.64-0.80; p < 0.0001), with no statistical difference between them (p for interaction = 0.41). Meta-regression further revealed no significant association between the prevalence of HF with reduced ejection fraction or diabetes and the effect size of SGLT2i. CONCLUSIONS: The treatment effects of SGLT2i were associated with a lower incidence of CV events, especially HF hospitalization, in patients with AF.


Subject(s)
Atrial Fibrillation , Diabetes Mellitus , Heart Failure , Sodium-Glucose Transporter 2 Inhibitors , Humans , Atrial Fibrillation/drug therapy , Sodium-Glucose Transporter 2 Inhibitors/therapeutic use , Randomized Controlled Trials as Topic , Heart Failure/drug therapy , Heart Failure/epidemiology
11.
J Intern Med ; 295(4): 557-568, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38111091

ABSTRACT

BACKGROUND: Effects of intensive blood pressure (BP) control on cognitive outcomes in patients with excess orthostatic BP changes are unclear. We aimed to evaluate whether orthostatic BP changes modified the effects of BP intervention on cognitive impairment. METHODS: We analyzed 8547 participants from the Systolic Blood Pressure Intervention Trial Memory and cognition IN Decreased Hypertension. Associations between orthostatic BP changes and incident cognitive outcomes were evaluated by restricted cubic spline curves based on Cox models. The interactions between orthostatic BP changes and intensive BP intervention were assessed. RESULTS: The U-shaped associations were observed between baseline orthostatic systolic BP changes and cognitive outcomes. However, there were insignificant interactions between either change in orthostatic systolic BP (P for interaction = 0.81) or diastolic BP (P for interaction = 0.32) and intensive BP intervention for the composite outcome of probable dementia or mild cognitive impairment (MCI). The hazard ratio of intensive versus standard target for the composite cognitive outcome was 0.82 (95% CI 0.50-1.35) in those with an orthostatic systolic BP reduction of >20 mmHg and 0.41 (95% CI 0.21-0.80) in those with an orthostatic systolic BP increase of >20 mmHg. Results were similar for probable dementia and MCI. The annual changes in global cerebral blood flow (P for interaction = 0.86) consistently favored intensive BP treatment across orthostatic systolic BP changes. CONCLUSION: Intensive BP control did not have a deteriorating effect on cognitive outcomes among hypertensive patients experiencing significant postural BP changes.


Subject(s)
Cognitive Dysfunction , Dementia , Hypertension , Hypotension, Orthostatic , Humans , Blood Pressure , Cognition , Hypertension/drug therapy , Hypotension, Orthostatic/psychology
12.
J Am Heart Assoc ; 12(24): e031269, 2023 Dec 19.
Article in English | MEDLINE | ID: mdl-38084708

ABSTRACT

BACKGROUND: The association between sodium-glucose cotransporter 2 inhibitors (SGLT2i) and atrial fibrillation (AF) recurrence after catheter ablation among patients with diabetes and AF remains unclear. METHODS AND RESULTS: Patients with AF undergoing initial catheter ablation with a history of diabetes from the China AF registry were included. Patients using SGLT2i were identified and matched by propensity score with non-SGLT2i patients in a 1:3 ratio. The main outcome was AF recurrence during the 18-month follow-up. A total of 138 patients with diabetes with SGLT2i therapy and 387 without SGLT2i were analyzed. AF recurrence occurred in 37 patients (26.8%) in the SGLT2i group and 152 patients (39.3%) in the non-SGLT2i group during a total of 593.3 person-years follow-up. The SGLT2i group was associated with lower AF recurrence compared with the non-SGLT2i group (hazard ratio, 0.63 [95% CI, 0.44-0.90], P=0.007). A total of 4 studies were analyzed in our meta-analysis demonstrating that SGLT2i was associated with lower AF recurrence after catheter ablation (odds ratio, 0.61 [95% CI, 0.54-0.69]; P<0.001, I2=0.0%). CONCLUSIONS: Our prospective study coupled with a meta-analysis demonstrated a lower risk of AF recurrence with the use of SGLT2i among patients with diabetes after AF ablation.


Subject(s)
Atrial Fibrillation , Catheter Ablation , Diabetes Mellitus , Humans , Atrial Fibrillation/drug therapy , Atrial Fibrillation/surgery , Atrial Fibrillation/complications , Propensity Score , Prospective Studies , Risk Factors , Treatment Outcome , Recurrence , Diabetes Mellitus/etiology , Catheter Ablation/adverse effects , Catheter Ablation/methods , Glucose , Sodium
13.
J Geriatr Cardiol ; 20(10): 707-715, 2023 Oct 28.
Article in English | MEDLINE | ID: mdl-37970223

ABSTRACT

BACKGROUND: Patients with atrial fibrillation (AF) and prior stroke history have a high risk of cardiovascular events despite anticoagulation therapy. It is unclear whether catheter ablation (CA) has further benefits in these patients. METHODS: AF patients with a previous history of stroke or systemic embolism (SE) from the prospective Chinese Atrial Fibrillation Registry study between August 2011 and December 2020 were included in the analysis. Patients were matched in a 1:1 ratio to CA or medical treatment (MT) based on propensity score. The primary outcome was a composite of all-cause death or ischemic stroke (IS)/SE. RESULTS: During a total of 4.1 ± 2.3 years of follow-up, the primary outcome occurred in 111 patients in the CA group (3.3 per 100 person-years) and in 229 patients in the MT group (5.7 per 100 person-years). The CA group had a lower risk of the primary outcome compared to the MT group [hazard ratio (HR) = 0.59, 95% CI: 0.47-0.74, P < 0.001]. There was a significant decreasing risk of all-cause mortality (HR = 0.43, 95% CI: 0.31-0.61, P < 0.001), IS/SE (HR = 0.73, 95% CI: 0.54-0.97, P = 0.033), cardiovascular mortality (HR = 0.32, 95% CI: 0.19-0.54, P < 0.001) and AF recurrence (HR = 0.33, 95% CI: 0.30-0.37, P < 0.001) in the CA group compared to that in the MT group. Sensitivity analysis generated consistent results when adjusting for time-dependent usage of anticoagulants. CONCLUSIONS: In AF patients with a prior stroke history, CA was associated with a lower combined risk of all-cause death or IS/SE. Further clinical trials are warranted to confirm the benefits of CA in these patients.

14.
Cell ; 186(23): 4996-5014.e24, 2023 11 09.
Article in English | MEDLINE | ID: mdl-37949056

ABSTRACT

A formal demonstration that mammalian pluripotent stem cells possess preimplantation embryonic cell-like (naive) pluripotency is the generation of chimeric animals through early embryo complementation with homologous cells. Whereas such naive pluripotency has been well demonstrated in rodents, poor chimerism has been achieved in other species including non-human primates due to the inability of the donor cells to match the developmental state of the host embryos. Here, we have systematically tested various culture conditions for establishing monkey naive embryonic stem cells and optimized the procedures for chimeric embryo culture. This approach generated an aborted fetus and a live chimeric monkey with high donor cell contribution. A stringent characterization pipeline demonstrated that donor cells efficiently (up to 90%) incorporated into various tissues (including the gonads and placenta) of the chimeric monkeys. Our results have major implications for the study of primate naive pluripotency and genetic engineering of non-human primates.


Subject(s)
Embryonic Stem Cells , Genetic Engineering , Haplorhini , Animals , Female , Pregnancy , Haplorhini/genetics , Live Birth , Mammals , Pluripotent Stem Cells , Primates , Genetic Engineering/methods
15.
Pacing Clin Electrophysiol ; 46(10): 1203-1211, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37736697

ABSTRACT

OBJECTIVE: Patients with atrial fibrillation (AF) are highly heterogeneous, and current risk stratification scores are only modestly good at predicting an individual's stroke risk. We aim to identify distinct AF clinical phenotypes with cluster analysis to optimize stroke prevention practices. METHODS: From the prospective Chinese Atrial Fibrillation Registry cohort study, we included 4337 AF patients with CHA2 DS2 -VASc≥2 for males and 3 for females who were not treated with oral anticoagulation. We randomly split the patients into derivation and validation sets by a ratio of 7:3. In the derivation set, we used outcome-driven patient clustering with metric learning to group patients into clusters with different risk levels of ischemic stroke and systemic embolism, and identify clusters of patients with low risks. Then we tested the results in the validation set, using the clustering rules generated from the derivation set. Finally, the survival decision tree was applied as a sensitivity analysis to confirm the results. RESULTS: Up to the follow-up of 1 year, 140 thromboembolic events (ischemic stroke or systemic embolism) occurred. After supervised metric learning from six variables involved in CHA2 DS2 -VASc scheme, we identified a cluster of patients (255/3035, 8.4%) at an annual thromboembolism risk of 0.8% in the derivation set. None of the patients in the low-risk cluster had prior thromboembolism, heart failure, diabetes, or age older than 70 years. After applying the regularities from metric learning on the validation set, we also identified a cluster of patients (137/1302, 10.5%) with an incident thromboembolism rate of 0.7%. Sensitivity analysis based on the survival decision tree approach selected a subgroup of patients with the same phenotypes as the metric-learning algorithm. CONCLUSIONS: Cluster analysis identified a distinct clinical phenotype at low risk of stroke among high-risk [CHA2 DS2 -VASc≥2 (3 for females)] patients with AF. The use of the novel analytic approach has the potential to prevent a subset of AF patients from unnecessary anticoagulation and avoid the associated risk of major bleeding.

16.
J Am Heart Assoc ; 12(16): e029623, 2023 08 15.
Article in English | MEDLINE | ID: mdl-37548160

ABSTRACT

Background The knowledge gap regarding whether the correlation between atrial fibrillation (AF) and dementia in observational studies is causation or driven by other shared risk factors remains substantially unfilled. Methods and Results We performed a comprehensive 2-sample Mendelian randomization study to evaluate the causal effect of AF on overall dementia and its subtypes, including vascular dementia, Alzheimer dementia, Lewy body dementia, and frontotemporal dementia. The primary results in inverse variance-weighted analyses were further validated by various Mendelian randomization sensitivity analyses. Additionally, we conducted multivariable Mendelian randomization to examine 10 candidate mediators of the causal association of AF and dementia. Genetic predisposition to AF was modestly associated with an increased risk of overall dementia (odds ratio, 1.140 [95% CI, 1.023-1.271]; P=0.018) and strongly associated with vascular dementia (odds ratio, 1.350 [95% CI, 1.076-1.695]; P=0.010). Genetically predicted AF indicated neutral effects on Alzheimer dementia, Lewy body dementia, and frontotemporal dementia. In multivariable Mendelian randomization analysis, the total effect of AF on overall dementia was remarkably attenuated by adjusting for genetic effect for ischemic stroke (odds ratio, 1.068 [95% CI, 0.953-1.197]; P=0.259) and low cardiac output (odds ratio, 1.046 [95% CI, 0.926-1.181]; P=0.475), indicating that the causal association of genetically predicted AF with dementia was potentially mediated by ischemic stroke and low cardiac output. The causal effect of genetically predicted AF on dementia was independent of cerebral small-vessel disease and brain volume phenotypes. Conclusions Our findings provided novel evidence supporting the causal effect of genetically predicted AF on dementia mediated by ischemic stroke and low cardiac output. Future clinical trials are warranted to evaluate the potential role of appropriate AF management in dementia prevention.


Subject(s)
Alzheimer Disease , Atrial Fibrillation , Dementia, Vascular , Frontotemporal Dementia , Ischemic Stroke , Lewy Body Disease , Humans , Atrial Fibrillation/diagnosis , Atrial Fibrillation/epidemiology , Atrial Fibrillation/genetics , Alzheimer Disease/genetics , Dementia, Vascular/diagnosis , Dementia, Vascular/epidemiology , Dementia, Vascular/genetics , Lewy Body Disease/complications , Mendelian Randomization Analysis , Frontotemporal Dementia/complications , Cardiac Output, Low/complications , Ischemic Stroke/complications , Polymorphism, Single Nucleotide , Genome-Wide Association Study/methods
17.
Hypertension ; 80(11): 2306-2314, 2023 11.
Article in English | MEDLINE | ID: mdl-37589154

ABSTRACT

BACKGROUND: Systolic blood pressure (SBP) time in target range (TTR) indicates the mean value, exposure time, and variability in blood pressure over time. The prognostic value of SBP TTR for incident atrial fibrillation (AF) in patients with hypertension is unclear. METHODS: We performed a post hoc analysis of SPRINT (Systolic Blood Pressure Intervention Trial), a randomized controlled trial comparing intensive (<120 mm Hg) and standard (<140 mm Hg) SBP interventions in participants with hypertension. SBP target ranges for intensive and standard arms were defined as 110 to 130 and 120 to 140 mm Hg, respectively. TTR was calculated by linear interpolation method using SBP from months 0 to 3. We used Cox proportional regression models to assess the association of SBP TTR with incident AF. RESULTS: Among 7939 participants included in this analysis, 187 incident AF cases occurred during follow-up. After multivariable adjustment, a 10% increase in SBP TTR was independently associated with a 7% lower risk of incident AF (hazard ratio, 0.93 [95% CI, 0.88-0.97]; P=0.003). The restricted spline curve depicted a linear and inverse relationship between SBP TTR and incident AF. Sensitivity analyses generated consistent results when calculating TTR over a longer period or setting target range as 110 to 140 mm Hg for the whole population. CONCLUSIONS: Higher SBP TTR independently predicts a lower risk of incident AF. Efforts to attain SBP within 110 to 140 mm Hg over time may be an effective strategy to prevent AF. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT01206062.


Subject(s)
Atrial Fibrillation , Hypertension , Humans , Blood Pressure/physiology , Atrial Fibrillation/diagnosis , Atrial Fibrillation/epidemiology , Atrial Fibrillation/etiology , Antihypertensive Agents/therapeutic use , Antihypertensive Agents/pharmacology , Risk Factors , Hypertension/drug therapy , Hypertension/epidemiology , Hypertension/complications
18.
J Clin Hypertens (Greenwich) ; 25(7): 591-600, 2023 07.
Article in English | MEDLINE | ID: mdl-37409556

ABSTRACT

The benefits of mHealth interventions in uncontrolled hypertension are unclear. To determine whether mHealth effectively improves the control rate of uncontrolled hypertension. PubMed, Web of Science, EMBASE, Scopus, and Cochrane Library were searched for randomized controlled trials (RCTs) from January 2007 to September 2022. The intervention group consisted of mHealth intervention, and the control group was usual care. Random-effects meta-analysis models were used to assess pooled mHealth intervention effects and CIs. The primary outcome was the blood pressure (BP) control rate of uncontrolled hypertension. The secondary outcome was the change of BP. Thirteen RCTs were included in this meta-analysis, of which eight reported the successful BP control rate, 13 reported the change of systolic blood pressure (SBP), and 11 reported the change in diastolic blood pressure (DBP). The mean age of trial participants ranged from 47.7 to 66.9 years old, with a female composition ratio of 40.0%-66.1%. The duration of follow-up ranged from 3 to 18 months. This study showed a more robust effect size for improving BP control rate by mHealth interventions than usual care (57.5% vs. 40.8% of successful control rate; odds ratio [OR], 2.19 [95% CI, 1.32-3.62]). Furthermore, mHealth significantly reduced SBP by 4.45 mm Hg and DBP by 2.47 mm Hg, and subgroup analysis did not observe the major source of heterogeneity. This meta-analysis found that mHealth could significantly improve the uncontrolled hypertension control rate and might be a feasible, acceptable, and effective tool for uncontrolled hypertension management.


Subject(s)
Hypertension , Telemedicine , Female , Humans , Middle Aged , Aged , Hypertension/therapy , Randomized Controlled Trials as Topic , Blood Pressure
19.
Europace ; 25(7)2023 07 04.
Article in English | MEDLINE | ID: mdl-37417712

ABSTRACT

AIMS: After radiofrequency catheter ablation (RFCA) of atrial fibrillation (AF), the effect of very-early (within 48 h) symptomatic recurrence (VESR) on late (after 3 months of RFCA) recurrence (LR) has been seldomly reported. We aimed to explore the relationship between VESR and LR among post-RFCA patients. METHODS AND RESULTS: This was a single-centre prospective cohort study that enrolled 6887 AF patients who received the first RFCA procedure from June 2018 to December 2021 at Beijing Anzhen Hospital. Patients were divided into four groups based on VESR and early (from 48 h to 3 months after RFCA) recurrence (ER): Group A (no VESR, no ER); Group B (VESR but no ER); Group C (ER but no VESR); and Group D (both VESR and ER). Three hundred and thirty (4.79%) patients experienced VESR (Groups B and D). With an average follow-up of 14.7 months after grouping, the Kaplan-Meier curve showed that LR risk in VESR patients was higher than in other patients (log-rank, P < 0.001), and the difference was significant in both paroxysmal (log-rank, P < 0.001) and persistent (log-rank, P < 0.001) AF patients (P for interaction = 0.118). In multivariate analysis, Groups B, C, and D were associated with a 2.161-, 5.409-, and 7.401-fold increase in the risk of LR, respectively. What is more, compared with Group A, VESR-atrial tachycardia and VESR-AF were related to a 3.467- and 5.564-fold LR risk, respectively. In VESR patients, classification based on ER and VESR modes improved the prediction potential of LR risk. CONCLUSION: Very-early symptomatic recurrence is associated with an increased risk of LR.


Subject(s)
Atrial Fibrillation , Catheter Ablation , Humans , Atrial Fibrillation/diagnosis , Atrial Fibrillation/surgery , Atrial Fibrillation/etiology , Prospective Studies , Treatment Outcome , Risk Factors , Time Factors , Recurrence , Catheter Ablation/adverse effects , Catheter Ablation/methods , Chronic Disease
20.
Pacing Clin Electrophysiol ; 46(8): 895-903, 2023 Aug.
Article in English | MEDLINE | ID: mdl-37433176

ABSTRACT

Bi-atrial tachycardia (BiAT) is not rare after extensive atrial ablation or cardiac surgery. The complexity of bi-atrial reentrant circuits poses a great challenge for clinical practice. With recent advances in mapping technologies, we are now able to characterize atrial activation in detail. However, given the involvement of both atria and multiple epicardial conductions, endocardial mapping for BiATs is not easy to understand. Knowledge of the atrial myocardial architecture is the foundation for the clinical management of BiATs; as it is required to understand the possible mechanism of the tachycardia and identify the optimal target of ablation. In this review we summarize current knowledge about the anatomy of interatrial connections as well as other epicardial fibers and discuss the interpretation of electrophysiological findings and ablation strategies for BiATs.

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