Adaptive translational pausing is a hallmark of the cellular response to severe environmental stress.

To survive, mammalian cells must adapt to environmental challenges. While the cellular response to mild stress has been widely studied, how cells respond to severe stress remains unclear. We show here that under severe hyperosmotic stress, cells enter a transient hibernation-like state in anticipation of recovery. We demonstrate this adaptive pausing response (APR) is a coordinated cellular response that limits ATP supply and consumption through mitochondrial fragmentation and widespread pausing of mRNA translation. This pausing is accomplished by ribosome stalling at translation initiation codons, which keeps mRNAs poised to resume translation upon recovery. We further show that recovery from severe stress involves ISR (integrated stress response) signaling that permits cell cycle progression, resumption of growth, and reversal of mitochondria fragmentation. Our findings indicate that cells can respond to severe stress via a hibernation-like mechanism that preserves vital elements of cellular function under harsh environmental conditions.

Synthesis of a monolayer fullerene network.

Two-dimensional (2D) carbon materials, such as graphene, have attracted particular attention owing to the exceptional carrier transport characteristics that arise from the unique π-electron system in their conjugated carbon network structure1-4. To complement zero-bandgap graphene, material scientists have devoted considerable effort to identifying 2D carbon materials5-8. However, it is a challenge to prepare large-sized single-crystal 2D carbon materials with moderate bandgaps5,9. Here we prepare a single-crystal 2D carbon material, namely monolayer quasi-hexagonal-phase fullerene (C60), with a large size via an interlayer bonding cleavage strategy. In this monolayer polymeric C60, cluster cages of C60 are covalently bonded with each other in a plane, forming a regular topology that is distinct from that in conventional 2D materials. Monolayer polymeric C60 exhibits high crystallinity and good thermodynamic stability, and the electronic band structure measurement reveals a transport bandgap of about 1.6 electronvolts. Furthermore, an asymmetric lattice structure endows monolayer polymeric C60 with notable in-plane anisotropic properties, including anisotropic phonon modes and conductivity. This 2D carbon material with a moderate bandgap and unique topological structure offers an interesting platform for potential application in 2D electronic devices.

A Unique ISR Program Determines Cellular Responses to Chronic Stress.

The integrated stress response (ISR) is a homeostatic mechanism induced by endoplasmic reticulum (ER) stress. In acute/transient ER stress, decreased global protein synthesis and increased uORF mRNA translation are followed by normalization of protein synthesis. Here, we report a dramatically different response during chronic ER stress. This chronic ISR program is characterized by persistently elevated uORF mRNA translation and concurrent gene expression reprogramming, which permits simultaneous stress sensing and proteostasis. The program includes PERK-dependent switching to an eIF3-dependent translation initiation mechanism, resulting in partial, but not complete, translational recovery, which, together with transcriptional reprogramming, selectively bolsters expression of proteins with ER functions. Coordination of transcriptional and translational reprogramming prevents ER dysfunction and inhibits "foamy cell" development, thus establishing a molecular basis for understanding human diseases associated with ER dysfunction.

Single-cell transcriptomic analysis in clear cell renal cell carcinoma: Deciphering the role of APP within the tumour microenvironment.

Clear cell renal cell carcinoma (ccRCC) represents a significant challenge in oncology, primarily due to its resistance to conventional therapies. Understanding the tumour microenvironment (TME) is crucial for developing new treatment strategies. This study focuses on the role of amyloid precursor protein (APP) in tumour-associated macrophages (TAMs) within the ccRCC TME, exploring its potential as a prognostic biomarker. Basing TAM-related genes, the prognostic model was important to constructed. Employing advanced single-cell transcriptomic analysis, this research dissects the TME of ccRCC at an unprecedented cellular resolution. By isolating and examining the gene expression profiles of individual cells, particularly focusing on TAMs, the study investigates the expression levels of APP and their association with the clinical outcomes of ccRCC patients. The analysis reveals a significant correlation between the expression of APP in TAMs and patient prognosis in ccRCC. Patients with higher APP expression in TAMs showed differing clinical outcomes compared to those with lower expression. This finding suggests that APP could serve as a novel prognostic biomarker for ccRCC, providing insights into the disease progression and potential therapeutic targets. This study underscores the importance of single-cell transcriptomics in understanding the complex dynamics of the TME in ccRCC. The correlation between APP expression in TAMs and patient prognosis highlights APP as a potential prognostic biomarker. However, further research is needed to validate these findings and explore the regulatory mechanisms and therapeutic implications of APP in ccRCC.

MAP4K4 exacerbates cardiac microvascular injury in diabetes by facilitating S-nitrosylation modification of Drp1.

Dynamin-related protein 1 (Drp1) is a crucial regulator of mitochondrial dynamics, the overactivation of which can lead to cardiovascular disease. Multiple distinct posttranscriptional modifications of Drp1 have been reported, among which S-nitrosylation was recently introduced. However, the detailed regulatory mechanism of S-nitrosylation of Drp1 (SNO-Drp1) in cardiac microvascular dysfunction in diabetes remains elusive. The present study revealed that mitogen-activated protein kinase kinase kinase kinase 4 (MAP4K4) was consistently upregulated in diabetic cardiomyopathy (DCM) and promoted SNO-Drp1 in cardiac microvascular endothelial cells (CMECs), which in turn led to mitochondrial dysfunction and cardiac microvascular disorder. Further studies confirmed that MAP4K4 promoted SNO-Drp1 at human C644 (mouse C650) by inhibiting glutathione peroxidase 4 (GPX4) expression, through which MAP4K4 stimulated endothelial ferroptosis in diabetes. In contrast, inhibition of MAP4K4 via DMX-5804 significantly reduced endothelial ferroptosis, alleviated cardiac microvascular dysfunction and improved cardiac dysfunction in db/db mice by reducing SNO-Drp1. In parallel, the C650A mutation in mice abolished SNO-Drp1 and the role of Drp1 in promoting cardiac microvascular disorder and cardiac dysfunction. In conclusion, our findings demonstrate that MAP4K4 plays an important role in endothelial dysfunction in DCM and reveal that SNO-Drp1 and ferroptosis activation may act as downstream targets, representing potential therapeutic targets for DCM.

Preparation of Ultrasmall AIE Nanoparticles with Tunable Molecular Packing via Freeze Assembly.

Advances in the development of aggregation-induced emission luminogens (AIEgens) depend on understanding how the molecular packing affects their luminescent properties and on making nanoparticles (NPs) with desired sizes. Although reported strategies have advanced the field, rational control of molecular packing and efficient fabrication of AIEgen NPs sub-5.5 nm in diameter remain pressing issues. Here we report a "freeze assembly" strategy, in which the diameter of AIEgen NPs can be precisely tuned from ∼3 nm to hundreds of nanometers, and a molecular packing in kinetically trapped states that are not easily captured by conventional assembly methods can be obtained, leading to tunable fluorescence emissions. Therefore, this study provides a significant tool to fabricate organic luminescent nanomaterials with diameters smaller than 5 nm, which is of critical importance for biomedical applications; meanwhile, tuning molecular packing in nanoparticles displaying different fluorescence may help to shed new light on the mechanism of AIEgens.

Fluacrypyrim Protects Hematopoietic Stem and Progenitor Cells against Irradiation via Apoptosis Prevention.

Ionizing radiation (IR)-induced hematopoietic injury has become a global concern in the past decade. The underlying cause of this condition is a compromised hematopoietic reserve, and this kind of hematopoietic injury could result in infection or bleeding, in addition to lethal mishaps. Therefore, developing an effective treatment for this condition is imperative. Fluacrypyrim (FAPM) is a recognized effective inhibitor of STAT3, which exhibits anti-inflammation and anti-tumor effects in hematopoietic disorders. In this context, the present study aimed to determine whether FAPM could serve as a curative agent in hematopoietic-acute radiation syndrome (H-ARS) after total body irradiation (TBI). The results revealed that the peritoneally injection of FAPM could effectively promote mice survival after lethal dose irradiation. In addition, promising recovery of peripheral blood, bone marrow (BM) cell counts, hematopoietic stem cell (HSC) cellularity, BM colony-forming ability, and HSC reconstituting ability upon FAPM treatment after sublethal dose irradiation was noted. Furthermore, FAPM could reduce IR-induced apoptosis in hematopoietic stem and progenitor cells (HSPCs) both in vitro and in vivo. Specifically, FAPM could downregulate the expressions of p53-PUMA pathway target genes, such as Puma, Bax, and Noxa. These results suggested that FAPM played a protective role in IR-induced hematopoietic damage and that the possible underlying mechanism was the modulation of apoptotic activities in HSCs.

Human plasma derived exosomes: Impact of active and passive drug loading approaches on drug delivery.

The aim of the current study was to explore the potential of human plasma-derived exosomes as versatile carriers for drug delivery by employing various active and passive loading methods. Exosomes were isolated from human plasma using differential centrifugation and ultrafiltration method. Drug loading was achieved by employing sonication and freeze thaw methods, facilitating effective drug encapsulation within exosomes for delivery. Each approach was examined for its effectiveness, loading efficiency and ability to preserve membrane stability. Methotrexate (MTX), a weak acid model drug was loaded at a concentration of 2.2 µM to exosomes underwent characterization using various techniques such as particle size analysis, transmission electron microscopy and drug loading capacity. Human plasma derived exosomes showed a mean size of 162.15 ± 28.21 nm and zeta potential of -30.6 ± 0.71 mV. These exosomes were successfully loaded with MTX demonstrated a better drug encapsulation of 64.538 ± 1.54 % by freeze thaw method in comparison 55.515 ± 1.907 % by sonication. In-vitro drug release displayed 60 % loaded drug released within 72 h by freeze thaw method that was significantly different from that by sonication method i.e., 99 % within 72 h (p value 0.0045). Moreover, cell viability of exosomes loaded by freeze thaw method was significantly higher than that by sonication method (p value 0.0091) suggested that there was membrane disruption by sonication method. In conclusion, this study offers valuable insights into the potential of human plasma-derived exosomes loaded by freeze thaw method suggest as a promising carrier for improved drug loading and maintenance of exosomal membrane integrity.

Dealloying-Induced Zeolite-like Metal Framework of AB2 Laves Phase Intermetallic Electrocatalysts.

Exploring an efficient and robust electrocatalyst for hydrogen evolution reaction (HER) at high pH and temperature holds the key to the industrial application of alkaline water electrolysis (AWE). Herein, we design an open tunnel structure by dealloying a series of Laves phase intermetallics, i.e., MCo2 and MRu0.25Co1.75 (M = Sc and Zr). The dealloying process can induce a zeolite-like metal framework for ScCo2 and ScRu0.25Co1.75 by stripping Sc metal from the center of a tunnel structure. This structural engineering significantly lowers their overpotentials at a current density of 500 mA/cm2 (η500) ca. 80 mV in 1.0 M KOH. Through a simple process, ScRu0.25Co1.75 can be easily decorated on a carbon cloth substrate and only requires 132 mV to reach 500 mA/cm2. More importantly it can maintain activity over 1000 h in industrial conditions (6.0 M KOH at 333 K), showing its potential for practical industrial applications.

Co-Immobilization of GOD & HRP on Y-Shaped DNA Scaffold and the Regulation of Inter-Enzyme Distance.

In multienzymes cascade reaction, the inter-enzyme spacing is supposed to be a factor affecting the cascade activity. Here, a simple and efficient Y-shaped DNA scaffold is assembled using two partially complementary DNA single strands on magnetic microspheres, which is used to coimmobilize glucose oxidase (GOD) and horseradish peroxidase (HRP). As a result, on poly(vinyl acetate) magnetic microspheres (PVAC), GOD/HRP-DNA@PVAC multienzyme system is obtained, which can locate GOD and HRP accurately and control the inter-enzyme distance precisely. The distance between GOD and HRP is regulated by changing the length of DNA strand. It showed that the cascade activity is significantly distance-dependent. Moreover, the inter-enzyme spacing is not the closer the better, and too short distance would generate steric hindrance between enzymes. The cascade activity reached the maximum value of 967 U mg-1 at 13.6 nm, which is 3.5 times higher than that of free enzymes. This is ascribed to the formation of substrate channeling.

Living alone and health-related quality of life among adults with obstructive sleep apnea in a single-center cohort study.

OBJECTIVE: To determine the impact of a solitary lifestyle on health-related quality of life (HRQoL) in adults with obstructive sleep apnea (OSA). METHODS: This was a prospective cohort study; patients diagnosed with OSA but not receiving continuous positive airway pressure (CPAP) therapy were enrolled in our study. These participants completed basic information and the Short Form-36 Health Survey (SF-36) at baseline and were divided into the living alone and living with others groups. Telephone follow-up was performed 1 year later to re-evaluate the SF-36. Differences in health status between and within groups were assessed. In addition, variables associated with changes in the health of the whole population were examined. RESULTS: A total of 402 patients with OSA were enrolled, including 120 in the living alone group and the rest in the living with others group. After a year, mental health scores of the living alone group decreased (55.7 ± 21.5 versus 54.1 ± 22.7, p = 0.001), while physical functioning scores of the living with others group increased significantly (82.1 ± 24.7 versus 82.6 ± 24.2, p = 0.006). In the whole population, the determinants of mental health change after 1 year from baseline were alcohol drinking (beta coefficient - 1.169, 95% CI - 2.03 to - 0.309, p = 0.008) and solitary living (beta coefficient - 1.135, 95% CI - 2.072 to - 0.199, p = 0.018). CONCLUSION: Regarding all initial variables, alcohol drinking and solitary living seem to be the predictors of mental health change of patients with OSA in China. We speculate that to improve the quality of life of such people, the medical staff could provide certain social support for them.

I-line photolithographic metalenses enabled by distributed optical proximity correction with a deep-learning model.

High pattern fidelity is paramount to the performance of metalenses and metasurfaces, but is difficult to achieve using economic photolithography technologies due to low resolutions and limited process windows of diverse subwavelength structures. These hurdles can be overcome by photomask sizing or reshaping, also known as optical proximity correction (OPC). However, the lithographic simulators critical to model-based OPC require precise calibration and have not yet been specifically developed for metasurface patterning. Here, we demonstrate an accurate lithographic model based on Hopkin's image formulation and fully convolutional networks (FCN) to control the critical dimension (CD) patterning of a near-infrared (NIR) metalens through a distributed OPC flow using i-line photolithography. The lithographic model achieves an average ΔCD/CD = 1.69% due to process variations. The model-based OPC successfully produces the 260 nm CD in a metalens layout, which corresponds to a lithographic constant k1 of 0.46 and is primarily limited by the resolution of the photoresist. Consequently, our fabricated NIR metalens with a diameter of 1.5 mm and numerical aperture (NA) of 0.45 achieves a measured focusing efficiency of 64%, which is close to the calculated value of 69% and among the highest reported values using i-line photolithography.

Triglyceride-glucose index and the risk of heart failure: Evidence from two large cohorts and a mendelian randomization analysis.

BACKGROUND: The relationship between triglyceride-glucose (TyG) index, an emerging marker of insulin resistance, and the risk of incident heart failure (HF) was unclear. This study thus aimed to investigate this relationship. METHODS: Subjects without prevalent cardiovascular diseases from the prospective Kailuan cohort (recruited during 2006-2007) and a retrospective cohort of family medicine patients from Hong Kong (recruited during 2000-2003) were followed up until December 31st, 2019 for the outcome of incident HF. Separate adjusted hazard ratios (aHRs) summarizing the relationship between TyG index and HF risk in the two cohorts were combined using a random-effect meta-analysis. Additionally, a two-sample Mendelian randomization (MR) of published genome-wide association study data was performed to assess the causality of observed associations. RESULTS: In total, 95,996 and 19,345 subjects from the Kailuan and Hong Kong cohorts were analyzed, respectively, with 2,726 cases of incident HF in the former and 1,709 in the latter. Subjects in the highest quartile of TyG index had the highest risk of incident HF in both cohorts (Kailuan: aHR 1.23 (95% confidence interval: 1.09-1.39), PTrend <0.001; Hong Kong: aHR 1.21 (1.04-1.40), PTrend =0.007; both compared with the lowest quartile). Meta-analysis showed similar results (highest versus lowest quartile: HR 1.22 (1.11-1.34), P < 0.001). Findings from MR analysis, which included 47,309 cases and 930,014 controls, supported a causal relationship between higher TyG index and increased risk of HF (odds ratio 1.27 (1.15-1.40), P < 0.001). CONCLUSION: A higher TyG index is an independent and causal risk factor for incident HF in the general population. CLINICAL TRIAL REGISTRATION: URL: https://www.chictr.org.cn ; Unique identifier: ChiCTR-TNRC-11,001,489.

eIF2A-knockout mice reveal decreased life span and metabolic syndrome.

Eukaryotic initiation factor 2A (eIF2A) is a 65 kDa protein that functions in minor initiation pathways, which affect the translation of only a subset of messenger ribonucleic acid (mRNAs), such as internal ribosome entry site (IRES)-containing mRNAs and/or mRNAs harboring upstream near cognate/non-AUG start codons. These non-canonical initiation events are important for regulation of protein synthesis during cellular development and/or the integrated stress response. Selective eIF2A knockdown in cellular systems significantly inhibits translation of such mRNAs, which rely on alternative initiation mechanisms for their translation. However, there exists a gap in our understanding of how eIF2A functions in mammalian systems in vivo (on the organismal level) and ex vivo (in cells). Here, using an eIF2A-knockout (KO) mouse model, we present evidence implicating eIF2A in the biology of aging, metabolic syndrome and central tolerance. We discovered that eIF2A-KO mice have reduced life span and that eIF2A plays an important role in maintenance of lipid homeostasis, the control of glucose tolerance, insulin resistance and also reduces the abundance of B lymphocytes and dendritic cells in the thymic medulla of mice. We also show the eIF2A KO affects male and female mice differently, suggesting that eIF2A may affect sex-specific pathways. Interestingly, our experiments involving pharmacological induction of endoplasmic reticulum (ER) stress with tunicamycin did not reveal any substantial difference between the response to ER stress in eIF2A-KO and wild-type mice. The identification of eIF2A function in the development of metabolic syndrome bears promise for the further identification of specific eIF2A targets responsible for these changes.

C-reactive protein and atrial fibrillation: Insights from epidemiological and Mendelian randomization studies.

BACKGROUND AND AIMS: This study aimed to investigate the role of C-reactive protein (CRP) in atrial fibrillation (AF) from epidemiological and genetic perspectives. METHODS AND RESULTS: Individual-level data from the Kailuan cohort recruited between 2006 and 2017 were included. Serum CRP levels were measured at baseline and at biennial follow-up visits, and incident AF was ascertained from biennial 12-lead ECG assessment and medical records. Cox proportional hazards models were used to assess the association between baseline CRP levels or cumulative exposure to CRP and incident AF. A meta-analysis including nine prospective cohort studies and our current study was also conducted. Mendelian randomization (MR) analysis was performed to evaluate the aetiological role of CRP in AF. In our observational study (n = 86,424), high baseline CRP levels (>3 mg/L), compared with low CRP (<1 mg/L), were not significantly associated with AF risk (HR: 1.18; 95% CI: 0.99-1.40). High cumulative exposure to CRP (HR: 1.49; 95%CI: 1.01-2.21) was significantly associated with an increased risk of AF. Our meta-analysis suggested a positive association between elevated CRP levels and incident AF (relative risk: 1.27; 95% CI: 1.14-1.42). However, no significant association between genetically determined CRP and AF risk was observed in the MR analysis. CONCLUSION: Evidence from observational studies suggested that elevated serum CRP levels were positively associated with incident AF, while the causal effects of CRP on AF were not supported by the MR analysis. CLINICAL TRIAL REGISTRATION: URL: https://www.chictr.org.cn; Unique identifier: ChiCTR-TNRC-11001489.

Assembly of Hexagonal Column Interpenetrated Spheres from Plant Polyphenol/Cationic Surfactants and Their Application as Antimicrobial Molecular Banks.

Microbial infections have become a great threat to human health and one of the main risks arises from direct contact with the surfaces contaminated by pathogenic microbes. Herein, a kind of hexagonal column interpenetrated spheres (HCISs) are fabricated by non-covalent assembly of plant gallic acid with quaternary ammonium surfactants. Different from one-time burst release of conventional antimicrobial agents, the HCIS acts like a "antimicrobial molecular bank" and releases the antimicrobial ingredients in a multistage way, leading to long-lasting antimicrobial performance. Taking advantage of strong hydrophobicity and adhesion, HCISs are applicable to various substrates and endowed with anti-water washing property, thus showing high in vitro antimicrobial efficiency (>99 %) even after being used for 10 cycles. Meanwhile, HCISs exhibit broad-spectrum antimicrobial activity against bacteria and fungi, and have good biocompatibility with mammalian cells. Such a low-cost and portable long-lasting antimicrobial agent meets the growing anti-infection demand in public spaces.

Bridging Interparticle Li+ Conduction in a Soft Ceramic Oxide Electrolyte.

Li+-conductive ceramic oxide electrolytes, such as garnet-structured Li7La3Zr2O12, have been considered as promising candidates for realizing the next-generation solid-state Li-metal batteries with high energy density. Practically, the ceramic pellets sintered at elevated temperatures are often provided with high stiffness yet low fracture toughness, making them too brittle for the manufacture of thin-film electrolytes and strain-involved operation of solid-state batteries. The ceramic powder, though provided with ductility, does not yield satisfactorily high Li+ conductivity due to poor ion conduction at the boundaries of ceramic particles. Here we show, with solid-state nuclear magnetic resonance, that a uniform conjugated polymer nanocoating formed on the surface of ceramic oxide particles builds pathways for Li+ conduction between adjacent particles in the unsintered ceramics. A tape-casted thin-film electrolyte (thickness: <10 µm), prepared from the polymer-coated ceramic particles, exhibits sufficient ionic conductivity, a high Li+ transference number, and a broad electrochemical window to enable stable cycling of symmetric Li/Li cells and all-solid-state rechargeable Li-metal cells.

Serial Cardiopulmonary Exercise Testing in Patients after Extracardiac Conduit Total Cavopulmonary Connection for Single-Ventricle Hearts: An Observational Study.

OBJECTIVE: To analyze the aerobic fitness and evolution of exercise tolerance in patients with single-ventricle physiology after total cavopulmonary connection (TCPC) with an extracardiac conduit (ECC). STUDY DESIGN: This retrospective cohort study included patients with previous ECC-TCPC who underwent cardiopulmonary exercise testing (CPET) between September 2010 and September 2019. Patients who completed at least 2 tests (≥6 months apart) with adequate levels of effort were recruited for the serial CPET evaluation. RESULTS: We identified 70 patients (50% male) with a mean age of 6.45 ± 5.14 years at ECC-TCPC and 15.67 ± 5.03 years at the initial CPET. The peak oxygen consumption (peak VO2) to predicted value (peak PD) was 55.90 ± 16.81%. Twenty of the 70 identified patients (50% male) were recruited for serial analysis. The average number of CPETs was 2.6 per patient. The average duration from the first CPET to the last CPET was 3.64 years. The peak VO2 and PD increased slowly, with mean rates of 38.77 ± 129.01 mL/min and 1.66 ± 6.40%, respectively, during the study period. CONCLUSIONS: Although the patients had lower exercise tolerance after ECC-TCPC compared with their normal peers, exercise tolerance appears to have been preserved over the adolescent period in those who underwent serial testing after ECC-TCPC.

Association between epicardial adipose tissue and blood pressure: A systematic review and meta-analysis.

AIMS: Epicardial adipose tissue has been reported to be associated with the development of cardiometabolic disease. Whether this is true for hypertension and non-dipper blood pressure remains controversial. Here, we conducted a systemic review and meta-analysis to evaluate the association between EAT and blood pressure. DATA SYNTHESIS: Pubmed, Embase, and Web of Science were searched for relevant papers. Studies reported on the difference of EAT thickness between hypertensive and normotensive patients, or those recorded odds ratio (OR) between EAT and hypertension were included. The standard mean difference (SMD) and ORs were extracted and pooled using a random-effects model respectively. We further assessed the effect of EAT on circadian rhythm of blood pressure by combining multiple-adjusted ORs for non-dipper blood pressure. Seven studies with an overall sample of 1089 patients reported the mean difference of EAT thickness between hypertensive and normotensive patients, and the hypertensive patients had higher EAT (SMD = 1.07; 95% CI: 0.66-1.48; I2 = 89.2%) compared with controls. However, the pooled association between EAT and hypertension from two studies was not significant (OR = 1.65, 95%CI 0.62-4.68; I2 = 87.5%). The summary risk effect of EAT on non-dipper blood pressure from six studies comprising1208 patients showed that each 1 mm increment of EAT was associated with a 2.55-fold risk of non-dipper blood pressure. CONCLUSION: Hypertensive patients tend to present higher EAT thickness near the right ventricular wall and increased EAT thickness might be associated with high risk of non-dipper blood pressure. Future researches are warranted to determine the causal link between EAT and hypertension and the underlying mechanism.

Serial cardiopulmonary exercise testing in an asymptomatic young female receiving percutaneous balloon dilatation for cor triatriatum sinistrum at an early age.

A young female was diagnosed as classic cor triatriatum sinistrum (CTS) at 38 months old incidentally and she received percutaneous catheter-based balloon dilatation twice at 41 and 48 months old. She took regular follow-up by echocardiography biannually with no re-stenosis of the orifice in the membrane between two chambers in the left atrium and she denied any cardiac-related symptoms. Serial cardiopulmonary exercise testing (CPET) by treadmill under Ramped-Bruce protocol was done at her 13, 19, and 23-year old. She could reach maximal effort and complete the three CPETs. No significant change of metabolic equivalent at anaerobic (MET) threshold, peak MET, and pulmonary function were noted in the serial CPETs and all of them were within normal limits comparing to the reference values of Chinese specific to her age. Our case report demonstrated that the concept of percutaneous catheter-based balloon dilatation of obstructive membrane for classic CTS without other associated congenital heart diseases is sound and feasible. The prognosis is well without re-obstruction and the cardiopulmonary fitness after that could be maintain as healthy peers for up to 18 years.