A novel temperature-preserved core chamber designed for depths exceeding 5000 m has been developed to enhance the scientific understanding of deep oil and gas reservoirs.This temperature-preserved core chamber employs...A novel temperature-preserved core chamber designed for depths exceeding 5000 m has been developed to enhance the scientific understanding of deep oil and gas reservoirs.This temperature-preserved core chamber employs an innovative vacuum layer for temperature preservation and is compatible with a temperature-pressure preserved coring system.The design principles and key parameters of the temperature-preserved core chamber were determined through static analysis.Numerical simulations assessed the mechanical properties of 70,85,and 100 MPa core chambers under conditions of 120-150℃.The results demonstrate that the temperature-preserved core chambers withstand the applied stresses without plastic deformation,and the vacuum layer maintains its integrity under these conditions.A 70 MPa class core chamber prototype was manufactured,and system integration tests were performed on a self-developed in-situ coring platform.The system demonstrated stable operation at 70 MPa for 120 min,with pressure fluctuations within 5%.Additionally,the integrated system operated without interference,enabling the successful extraction of cores with a 50 mm diameter.These findings provide valuable theoretical guidance and design recommendations for advancing oil and gas in-situ temperature-pressure preserved coring technologies in high-temperature and high-pressure environments.展开更多
Heart failure(HF)with preserved ejection fraction(HFpEF)has exceeded HF with reduced ejection fraction(HFrEF),becoming the most common type of HF.Unlike HFrEF,HFpEF is primarily a chronic low-grade inflammatory proces...Heart failure(HF)with preserved ejection fraction(HFpEF)has exceeded HF with reduced ejection fraction(HFrEF),becoming the most common type of HF.Unlike HFrEF,HFpEF is primarily a chronic low-grade inflammatory process closely associated with metabolic disorders.The coexistence of HFpEF and metabolic dysfunction-associated steatotic liver disease(MASLD)presents significant clinical challenges due to shared metabolic pathophysiology and complex inter-play.Management strategies for HFpEF and MASLD remain challenging.Sodium-glucose cotransporter 2 inhibitors have shown benefits in managing both conditions.Additionally,glucagon-like peptide-1 receptor agonists are being actively investigated for their potential benefits,particularly in MASLD.A comprehensive,patient-centered approach that combines metabolic and cardiova-scular care is essential for improving outcomes in patients with HFpEF and MASLD,addressing the global metabolic health challenges.展开更多
Background Organic acids(OA)and maternal nutritional strategies have been demonstrated to promote piglet health and development.The objective of this study was to investigate the effects of incorporating OA-preserved ...Background Organic acids(OA)and maternal nutritional strategies have been demonstrated to promote piglet health and development.The objective of this study was to investigate the effects of incorporating OA-preserved cereal grains into sow diets during late gestation and lactation,aiming to reduce the metabolic demands of lactation while optimising offspring development and growth until slaughter.The experiment compared OA-preserved wheat and barley to conventionally dried grains,focusing on sow and offspring performance,as well as their faecal microbiota during lactation.Forty sows were blocked based on parity,body weight and back fat thickness on d 100 of gestation and assigned to one of two diets:a dried grain lactation diet and a preserved grain lactation diet.Sow faecal samples were collected at farrowing for the coefficient of apparent total tract digestibility(CATTD)of nutrients and microbial analysis.Offspring faecal samples were collected on d 10 postpartum and at weaning(d 26 postpartum)for microbial analysis.Results Sow body weight,back fat changes,gestation and lactation length,total piglets born,wean-to-oestrus interval,and lactation efficiency were unaffected by sow diet(P>0.05).However,sows offered the preserved grain diet exhibited improved CATTD of dry matter,nitrogen,gross energy,and neutral detergent fibre(P<0.05).While no maternal effect was observed on offspring growth during lactation(P>0.05),pigs from sows offered the preserved grain diet showed improved growth and feed efficiency from weaning until slaughter(d 168)compared to those from sows offered the dried grain diet(P<0.05).The preserved grain diet also reduced the abundance of Proteobacteria in sow faeces at farrowing and in their offspring on d 10 postpartum,and improved piglet faecal scores throughout lactation(P=0.05).At weaning,piglets from sows offered the preserved grain diet exhibited an increased abundance of Lactobacillus and reduced abundance of Alistipes in their faeces(P<0.05).Conclusion OA-preserved grains enhanced the CATTD of nutrients in sows,promoted healthier piglet faecal scores during lactation,and improved offspring growth performance post-weaning,potentially linked to beneficial changes observed in the faecal microbiota of sows and their offspring during lactation.展开更多
BACKGROUND Obesity has become a serious public health issue,significantly elevating the risk of various complications.It is a well-established contributor to Heart failure with preserved ejection fraction(HFpEF).Evalu...BACKGROUND Obesity has become a serious public health issue,significantly elevating the risk of various complications.It is a well-established contributor to Heart failure with preserved ejection fraction(HFpEF).Evaluating HFpEF in obesity is crucial.Epicardial adipose tissue(EAT)has emerged as a valuable tool for validating prognostic biomarkers and guiding treatment targets.Hence,assessing EAT is of paramount importance.Cardiovascular magnetic resonance(CMR)imaging is acknowledged as the gold standard for analyzing cardiac function and mor-phology.We hope to use CMR to assess EAT as a bioimaging marker to evaluate HFpEF in obese patients.AIM To assess the diagnostic utility of CMR for evaluating heart failure with preserved ejection fraction[HFpEF;left ventricular(LV)ejection fraction≥50%]by measuring the epicardial adipose tissue(EAT)volumes and EAT mass in obese patients.METHODS Sixty-two obese patients were divided into two groups for a case-control study based on whether or not they had heart failure with HFpEF.The two groups were defined as HFpEF+and HFpEF-.LV geometry,global systolic function,EAT volumes and EAT mass of all subjects were obtained using cine magnetic resonance sequences.RESULTS Forty-five patients of HFpEF-group and seventeen patients of HFpEF+group were included.LV mass index(g/m2)of HFpEF+group was higher than HFpEF-group(P<0.05).In HFpEF+group,EAT volumes,EAT volume index,EAT mass,EAT mass index and the ratio of EAT/[left atrial(LA)left-right(LR)diameter]were higher compared to HFpEF-group(P<0.05).In multivariate analysis,Higher EAT/LA LR diameter ratio was associated with higher odds ratio of HFpEF.CONCLUSION EAT/LA LR diameter ratio is highly associated with HFpEF in obese patients.It is plausible that there may be utility in CMR for assessing obese patients for HFpEF using EAT/LA LR diameter ratio as a diagnostic biomarker.Further prospective studies,are needed to validate these proof-of-concept findings.展开更多
Using pressure-preserved coring technique to determine in-situ gas content provides a more precise assessment of gas resource reserves and safeguard of mining safety in coal seams. How coring technique and depth affec...Using pressure-preserved coring technique to determine in-situ gas content provides a more precise assessment of gas resource reserves and safeguard of mining safety in coal seams. How coring technique and depth affect the determination of gas content is unclear due to borehole zoning rupture caused by roadway excavation and drilling disturbance. To this end, a proposed coupling model of stress distribution and gas migration was simulated and validated by FLAC^(3D) and COMSOL Multiphysics considering superposition effects of roadway excavation and drilling disturbance. The findings indicate that the roadway surrounding rock displays distinct zoning features including stress relief zone, stress concentration zone that is composed of plastic zone, elastic zone, and original stress zone;and the broken situations depending on the borehole peeping are consistent with the corresponding simulation results.On this basis, this study proposes a set of drilling coring depth calculation and prediction model for the gas desorption affected area under engineering disturbance. Optimal depth of coring drilling is not only approach to the in-situ coal bulk, but also can get the balance of the drilling workload and cost controlling. According to the typical mine site geological conditions and the numerical simulation results in this study, if the roadway excavation time is ~1 year, it is recommended that the pressure-preserved coring depth should be greater than 17 m.展开更多
In heart failure with preserved ejection fraction,significant left ventricular diastolic abnormalities are present,despite a normal systolic ejection fraction.This article will consider whether this is consistent with...In heart failure with preserved ejection fraction,significant left ventricular diastolic abnormalities are present,despite a normal systolic ejection fraction.This article will consider whether this is consistent with the law of conservation of energy,also know as the first law of thermodynamics.展开更多
Heart failure (HF) is a chronic condition characterized by the heart’s inability to pump blood effectively. Hypertension is a frequent contributing factor. The reduced cardiac output leads to fluid accumulation, caus...Heart failure (HF) is a chronic condition characterized by the heart’s inability to pump blood effectively. Hypertension is a frequent contributing factor. The reduced cardiac output leads to fluid accumulation, causing respiratory distress and chest pain. Ejection fraction (EF), a measure of the left ventricle’s pumping capacity, is crucial in HF diagnosis. HF with reduced EF (HFrEF) is defined by an EF below 40%, often caused by coronary artery disease—approximately half of all HF patients present with HFrEF. The remaining cases encompass HF with mid-range EF (40% - 50%) or HF with preserved EF (HFpEF, EF ≥ 50%).展开更多
Background:Formononetin(FMN)has beneficial effects in cardiovascular diseases but its functions and mechanisms in heart failure with preserved ejection fraction(HFpEF)remain unclear.This study aimed at determining whe...Background:Formononetin(FMN)has beneficial effects in cardiovascular diseases but its functions and mechanisms in heart failure with preserved ejection fraction(HFpEF)remain unclear.This study aimed at determining whether FMN ameliorated HFpEF-induced cardiac dysfunction and exploring its underlying mechanisms.Methods:The mouse model of HFpEF was established through uninephrectomy surgery and d-aldosterone infusion in C57BL/6 mice.Cardiac remodeling and potential mechanisms of FMN in HFpEF were assessed by histological analysis,immunofluorescence,echocardiography,real-time PCR and western blotting sequentially.Results:FMN prevented myocardial dysfunction,fibrosis and cardiomyocyte apoptosis.The mRNA levels of left ventricular hypertrophy markers were increased in HFpEF mice but they remained unchanged in FMN-treated mice.In addition,the expression levels of PPARαand PGC-1 were increased in HFpEF mice for FMN treatment.The PPARα-PGC-1 complex affected the expression of fatty acid content and encoded enzymes in glucose metabolism.Both the hypertrophy and metabolic impairment due to FMN in HFpEF mice were alleviated after the addition of PPARαantagonist GW6471.Conclusion:In conclusion,FMN could prevent the cardiac hypertrophy in HFpEF mice by activating the PPARα/PGC-1 pathway and regulating energy metabolism,which provides a new therapeutic strategy for HFpEF patients.展开更多
With the prevalence of the Internet of Things(IoT)systems,smart cities comprise complex networks,including sensors,actuators,appliances,and cyber services.The complexity and heterogeneity of smart cities have become v...With the prevalence of the Internet of Things(IoT)systems,smart cities comprise complex networks,including sensors,actuators,appliances,and cyber services.The complexity and heterogeneity of smart cities have become vulnerable to sophisticated cyber-attacks,especially privacy-related attacks such as inference and data poisoning ones.Federated Learning(FL)has been regarded as a hopeful method to enable distributed learning with privacypreserved intelligence in IoT applications.Even though the significance of developing privacy-preserving FL has drawn as a great research interest,the current research only concentrates on FL with independent identically distributed(i.i.d)data and few studies have addressed the non-i.i.d setting.FL is known to be vulnerable to Generative Adversarial Network(GAN)attacks,where an adversary can presume to act as a contributor participating in the training process to acquire the private data of other contributors.This paper proposes an innovative Privacy Protection-based Federated Deep Learning(PP-FDL)framework,which accomplishes data protection against privacy-related GAN attacks,along with high classification rates from non-i.i.d data.PP-FDL is designed to enable fog nodes to cooperate to train the FDL model in a way that ensures contributors have no access to the data of each other,where class probabilities are protected utilizing a private identifier generated for each class.The PP-FDL framework is evaluated for image classification using simple convolutional networks which are trained using MNIST and CIFAR-10 datasets.The empirical results have revealed that PF-DFL can achieve data protection and the framework outperforms the other three state-of-the-art models with 3%–8%as accuracy improvements.展开更多
Traditional pre-stack depth migration can only provide subsurface structural information. However, simple structure information is insufficient for petroleum exploration which also needs amplitude information proporti...Traditional pre-stack depth migration can only provide subsurface structural information. However, simple structure information is insufficient for petroleum exploration which also needs amplitude information proportional to reflection coefficients. In recent years, pre-stack depth migration algorithms which preserve amplitudes and based on the one- way wave equation have been developed. Using the method in the shot domain requires a deconvolution imaging condition which produces some instability in areas with complicated structure and dramatic lateral variation in velocity. Depth migration with preserved amplitude based on the angle domain can overcome the instability of the one-way wave migration imaging condition with preserved amplitude. It can also offer provide velocity analysis in the angle domain of common imaging point gathers. In this paper, based on the foundation of the one-way wave continuation operator with preserved amplitude, we realized the preserved amplitude prestack depth migration in the angle domain. Models and real data validate the accuracy of the method.展开更多
As shallow resources are increasingly depleted,the mechanics'theory and testing technology of deep insitu rock has become urgent.Traditional coring technologies obtain rock samples without retaining the in-situ en...As shallow resources are increasingly depleted,the mechanics'theory and testing technology of deep insitu rock has become urgent.Traditional coring technologies obtain rock samples without retaining the in-situ environmental conditions,leading to distortion of the measured parameters.Herein,a coring and testing systems retaining in-situ geological conditions is presented:the coring system that obtains in-situ rock samples,and the transfer and testing system that stores and analyzes the rocks under a reconstructed environment.The ICP-Coring system mainly consists of the pressure controller,active insulated core reactor and insulation layer and sealing film.The ultimate bearing strength of 100 MPa for pressurepreservation,temperature control accuracy of 0.97%for temperature-retained are realized.CH_(4)and CO permeability of the optimized sealing film are as low as 3.85 and 0.33 ppm/min.The average tensile elongation of the film is 152.4%and the light transmittance is reduced to 0%.Additionally,the pressure and steady-state temperature accuracy for reconstructing the in-situ environment of transfer and storage system up to 1%and±0.2 is achieved.The error recorded of the noncontact sensor ring made of lowdensity polymer is less than 6%than that of the contact test.The system can provide technical support for the deep in-situ rock mechanics research,improving deep resource acquisition capabilities and further clarifying deep-earth processes.展开更多
micro RNAs(mi RNAs) are powerful regulators of posttranscriptional gene expression and play an important role in pathophysiological processes. Circulating mi RNAs can be quantified in body liquids and are promising bi...micro RNAs(mi RNAs) are powerful regulators of posttranscriptional gene expression and play an important role in pathophysiological processes. Circulating mi RNAs can be quantified in body liquids and are promising biomarkers in numerous diseases. In cardiovascular disease mi RNAs have been proven to be reliable diagnostic biomarkers for different disease entities. In cardiac fibrosis(CF) and heart failure(HF) dysregulated circulating mi RNAs have been identified,indicating their promising applicability as diagnostic biomarkers. Some mi RNAs were successfully tested in risk stratification of HF implementing their potential use as prognostic biomarkers. In this respect mi RNAs might soon be implemented in diagnostic clinical routine. In the young field of mi RNA based research advances have been made in identifying mi RNAs as potential targets for the treatment of experimental CF and HF. Promising study results suggest their potential future application as therapeutic agents in treatment of cardiovascular disease. This article summarizes the current state of the various aspects of mi RNA research in the field of CF and HF with reduced ejection fraction as well as preserved ejection fraction. The review provides an overview of the application of circulating mi RNAs as biomarkers in CF and HF and current approaches to therapeutically utilize mi RNAs in this field of cardiovascular disease.展开更多
Traditional Chinese preserved egg products have exhibited some anti-inflammatory effects,but their mechanisms of action remain unknown.This study aimed to investigate the anti-inflammatory effects of preserved egg whi...Traditional Chinese preserved egg products have exhibited some anti-inflammatory effects,but their mechanisms of action remain unknown.This study aimed to investigate the anti-inflammatory effects of preserved egg white(PEW)treatment on dextran sulfate sodium(DSS)-induced colitis in mice and the underlying mechanisms.The results showed that treatment with PEW in mice with DSS-induced colitis for 14 days effectively improved the clinical signs,inhibited the secretion and gene expression of pro-inflammatory cytokines,and reduced myeloperoxidase(MPO)activity and oxidative stress levels.In addition,western blotting results showed that PEW significantly suppressed DSS-induced phosphorylation levels of nuclear factor-kappa B(NF-κB)p65 and p38 mitogen-activated protein kinase(MAPK)in colon tissues of mice with colitis.PEW also enhanced the production of short-chain fatty acids(SCFAs)and modulated gut microbiota composition in mice with DSS-induced colitis,including increasing the relative abundance of beneficial bacteria Lachnospiraceae,Ruminococcaceae and Muribaculaceae,and reducing the relative abundance of harmful bacteria Proteobacteria.Taken together,our study demonstrated that preserved egg white could alleviate DSS-induced colitis in mice through the reduction of oxidative stress,modulation of inflammatory cytokines,NF-κB,MAPK and gut microbiota composition.展开更多
Heart failure with preserved ejection fraction(HFPEF)is common and represents a major challenge in cardiovascular medicine.Most of the current treatment of HFPEF is based on morbidity benefits and symptom reduction.Va...Heart failure with preserved ejection fraction(HFPEF)is common and represents a major challenge in cardiovascular medicine.Most of the current treatment of HFPEF is based on morbidity benefits and symptom reduction.Various pharmacological interventions available for heart failure with reduced ejection fraction have not been supported by clinical studies for HFPEF.Addressing the specific aetiology and aggressive risk factor modification remain the mainstay in the treatment of HFPEF.We present a brief overview of the currently recommended therapeutic options with available evidence.展开更多
Background Endogenous aldehyde damages DNA and potentiates an ageing phenotype. The aldehyde dehydrogenase 2(ALDH2) rs671 polymorphism has a prevalence of 30%–50% in Asian populations. In this study, we aimed to anal...Background Endogenous aldehyde damages DNA and potentiates an ageing phenotype. The aldehyde dehydrogenase 2(ALDH2) rs671 polymorphism has a prevalence of 30%–50% in Asian populations. In this study, we aimed to analyze risk factors contributing to the development of heart failure with preserved ejection fraction(HFpEF) along with the genetic exposure in Chinese patients hospitalized with cardiovascular diseases(CVD). Methods From July 2017 to October 2018, a total of 770 consecutive Chinese patients with normal left ventricular ejection fractions(LVEF) and established CVD(hypertension, coronary heart diseases, or diabetes) were enrolled in this prospective cross-sectional study. HFpEF was defined by the presence of at least one of symptom(dyspnoea and fatigue) or sign(rales and ankle swelling) related to heart failure;N-terminal pro-B-Type natriuretic peptide(NT pro-BNP ≥ 280 pg/mL);LVEF ≥ 50%;and at least one criterion related to elevated ventricular filling pressure or diastolic dysfunction(left atrial diameter > 40 mm, E/E’ ≥ 13, E’/A’ < 1 or concurrent atrial fibrillation). Logistic regression was performed to yield adjusted odds ratios(ORs) for HFp EF incidence associated with traditional and/or genetic exposures. Results Finally, among 770 patients with CVD, 92(11.9%) patients were classified into the HFpEF group according to the diagnostic criteria. The mean age of the participants was 67 ± 12 years, and 278(36.1%) patients were females. A total of 303(39.4%) patients were ALDH2*2 variant carriers. In the univariate analysis, eight exposures were found to be associated with HFpEF: atrial fibrillation, ALDH2*2 variants, hypertension, age, anaemia, smoking, alcohol consumption and sex. Multivariable logistic regression showed that 4 ‘A’ variables(atrial fibrillation, ALDH2*2 variants, age and anaemia) were significantly associated with an increased risk of HFpEF. Atrial fibrillation was associated with a 3.8-fold increased HFpEF risk(95% CI: 2.21–6.61, P < 0.001), and the other three exposures associated with increased HFpEF risk were the ALDH2*2 variant(OR = 2.41, 95% CI: 1.49–3.87, P < 0.001), age(OR = 2.14, 95% CI: 1.27–3.60, P = 0.004), and anaemia(OR = 1.79, 95% CI: 1.05–3.03, P = 0.032). These four variables predicted HFpEF incidence in Chinese CVD patients(C-statistic = 0.745, 95% CI: 0.691–0.800, P < 0.001). Conclusions 4 A traits(atrial fibrillation, ALDH2*2 variants, age and anaemia) were associated with an increased risk of HFpEF in Chinese CVD patients. Our results provide potential clues to the aetiology, pathophysiology and therapeutic targets of HFpEF.展开更多
Heart failure(HF) is the leading cause of hospitalization among older adults and the prevalence is growing with the aging populations in the Western countries. Epidemiologic reports suggest that approximately 50% of p...Heart failure(HF) is the leading cause of hospitalization among older adults and the prevalence is growing with the aging populations in the Western countries. Epidemiologic reports suggest that approximately 50% of patients who have signs or symptoms of HF have preserved left ventricular ejection fraction. This HF type predominantly affects women and the elderly with other co-morbidities, such as diabetes, hypertension, and overt volume status. Most of the current treatment strategies are based on morbidity benefits such as quality of life and reduction of clinical HF symptoms. Treatment of patients with HF with preserved ejection fraction displayed disappointing results from several large randomized controlled trials. The heterogeneity of HF with preserved ejection fraction, understood as complex syndrome, seems to be one of the primary reasons. Here, we present an overview of the current management strategies with available evidence and new therapeutic approach from drugs currently in clinical trials, which target diastolic dysfunction, chronotropic incompetence, and risk factor management. We provide an outline and interpretation of recent clinical trials that failed to improve outcome and survival in patients with HF with preserved ejection fraction.展开更多
Objective To determine the effect of the phosphodiesterase-5 inhibitor sildenafil compared with placebo on exercise capacity and clinical status in HFPEF. Design Multicenter, double-blind, placebo-controlled, paralle...Objective To determine the effect of the phosphodiesterase-5 inhibitor sildenafil compared with placebo on exercise capacity and clinical status in HFPEF. Design Multicenter, double-blind, placebo-controlled, parallel-group, randomized clinical trial of 216 sta- ble outpatients with HF, ejection fraction ≥ 50%, elevated N-terminal brain-type natriuretic peptide or elevat- ed invasively measured filling pressures, and reduced exercise capacity. Participants were randomized from October 2008 through February 2012 at 26 centers in North America. Follow-up was through August 30, 2012.展开更多
With the launch of sacubitril/valsartan(ARNI),there are new options for the treatment of heart failure(HF).However,ARNI is currently only used in HF patients with reduced ejection fraction(HFrEF).No evidence shows tha...With the launch of sacubitril/valsartan(ARNI),there are new options for the treatment of heart failure(HF).However,ARNI is currently only used in HF patients with reduced ejection fraction(HFrEF).No evidence shows that no modern treatment can reduce mortality in HF patients with preserved ejection fraction(HFpEF).Therefore,it is urgently necessary clarify whether ARNI can be used in the treatment of HFpEF.In the present study,we summarized the research progress of ARNI in the treatment of HFpEF.展开更多
Objective Heart failure(HF)is divided into two types:Heart failure with reduced ejection fraction(HFrEF)and heart failure with preserved ejection fraction(HFpEF).The latter always results in diastolic dysfunction,char...Objective Heart failure(HF)is divided into two types:Heart failure with reduced ejection fraction(HFrEF)and heart failure with preserved ejection fraction(HFpEF).The latter always results in diastolic dysfunction,characterized by changes in mechanical properties.The objective of this study is to build a finite element(FE)model of HFpEF and analyze diastolic and systolic function in rats.Methods Ten Dahl salt-sensitive rats were fed either a low-salt(LS)(n=5)or highsalt(HS)(n=5)diet beginning at 7 weeks of age and scanned by ultrasonic machine at 14 weeks of age.A non-linear FE model of the left ventricle(LV)was built from cardiac echo images at end-diastole and passive material properties of the LV were prescribed using Fung’s transversely isotropic constitutive law.Fiber angles of the endocardium and epicardium were prescribed as 53°°and-52°,respectively,with respect to the circumferential direction and varied linearly through the LV wall.The method developed by Krishnamurthywas used to determine the unloaded geometry to estimate the Fung passive material parameters.LV end-diastolic pressure(EDP)was determined from the measured pressure waves and applied to the endocardium at the unloaded geometry to simulate passive filling.Active material properties of the LV were prescribed using Guccione’s time-varying elastance model and maximum isometric tension was scaled to match the measured peak systolic pressure.The finite element model was then coupled to the Windkessel model,whose parameters were adjusted to the measured hemodynamics.Results Measured LVEDPs of LS and HS rats were 4.9±3.4 mmHg and 13.2±5.4 mmHg(P-0.030 8),respectively.End-diastolic Cauchy stress along the fiber direction for LS rats was significantly lower than for HS rats(0.91±0.60 kPa vs 3.00±0.63 kPa,P=0.001 4)and there was a similar trend in end-diastolic Green Strain along the fiber direction(0.058±0.003 vs 0.072±0.010,P=0.012 8,Figure 1b),as well.There was no distinctive difference between end-systolic Cauchy stress along the fiber direction for LS rats and HS rats(17.2±4.3 kPa vs 17.2±5.5 kPa,P=0.991 9)but end-systolic Green Strain along the fiber direction for LS rats was significantly higher than for HS rats(-0. 108±0.017 vs-0.065±0.024,negative sign represents direction).Conclusions For rats with HFpEF,it is the elevated LVEDP that induces the increase in end-diastolic stress and strain,thereby leading to diastolic dysfunction.Because of the preserved ejection fraction,HFpEF has less effect on systolic function.展开更多
Heart failure with preserved ejection fraction(HFpEF)is a heterogeneous syndrome with various comorbidities,multiple cardiac and extracardiac pathophysiologic abnormalities,and diverse phenotypic presentations.Since H...Heart failure with preserved ejection fraction(HFpEF)is a heterogeneous syndrome with various comorbidities,multiple cardiac and extracardiac pathophysiologic abnormalities,and diverse phenotypic presentations.Since HFpEF is a heterogeneous disease with different phenotypes,individualized treatment is required.HFpEF with type 2 diabetes mellitus(T2DM)represents a specific phenotype of HFpEF,with about 45%-50% of HFpEF patients suffering from T2DM.Systemic inflammation associated with dysregulated glucose metabolism is a critical pathological mechanism of HFpEF with T2DM,which is intimately related to the expansion and dysfunction(inflammation and hypermetabolic activity)of epicardial adipose tissue(EAT).EAT is well established as a very active endocrine organ that can regulate the pathophysiological processes of HFpEF with T2DM through the paracrine and endocrine mechanisms.Therefore,suppressing abnormal EAT expansion may be a promising therapeutic strategy for HFpEF with T2DM.Although there is no treatment specifically for EAT,lifestyle management,bariatric surgery,and some pharmaceutical interventions(anti-cytokine drugs,statins,proprotein convertase subtilisin/kexin type 9 inhibitors,metformin,glucagon-like peptide-1 receptor agonists,and especially sodium-glucose cotransporter-2 inhibitors)have been shown to attenuate the inflammatory response or expansion of EAT.Importantly,these treatments may be beneficial in improving the clinical symptoms or prognosis of patients with HFpEF.Accordingly,well-designed randomized controlled trials are needed to validate the efficacy of current therapies.In addition,more novel and effective therapies targeting EAT are needed in the future.展开更多
基金the financial support from the National Key R&D Program of China(No.2022YFB3706604)the National Natural Science Foundation of China(52304033)+2 种基金the National Natural Science Foundation of China(No.51827901)Sichuan Science and Technology Program(2023NSFSC0790)China Postdoctoral Science Foundation(No.2023M742446)。
文摘A novel temperature-preserved core chamber designed for depths exceeding 5000 m has been developed to enhance the scientific understanding of deep oil and gas reservoirs.This temperature-preserved core chamber employs an innovative vacuum layer for temperature preservation and is compatible with a temperature-pressure preserved coring system.The design principles and key parameters of the temperature-preserved core chamber were determined through static analysis.Numerical simulations assessed the mechanical properties of 70,85,and 100 MPa core chambers under conditions of 120-150℃.The results demonstrate that the temperature-preserved core chambers withstand the applied stresses without plastic deformation,and the vacuum layer maintains its integrity under these conditions.A 70 MPa class core chamber prototype was manufactured,and system integration tests were performed on a self-developed in-situ coring platform.The system demonstrated stable operation at 70 MPa for 120 min,with pressure fluctuations within 5%.Additionally,the integrated system operated without interference,enabling the successful extraction of cores with a 50 mm diameter.These findings provide valuable theoretical guidance and design recommendations for advancing oil and gas in-situ temperature-pressure preserved coring technologies in high-temperature and high-pressure environments.
基金Supported by Wenzhou Science Technology Bureau Foundation,No.2022Y0726.
文摘Heart failure(HF)with preserved ejection fraction(HFpEF)has exceeded HF with reduced ejection fraction(HFrEF),becoming the most common type of HF.Unlike HFrEF,HFpEF is primarily a chronic low-grade inflammatory process closely associated with metabolic disorders.The coexistence of HFpEF and metabolic dysfunction-associated steatotic liver disease(MASLD)presents significant clinical challenges due to shared metabolic pathophysiology and complex inter-play.Management strategies for HFpEF and MASLD remain challenging.Sodium-glucose cotransporter 2 inhibitors have shown benefits in managing both conditions.Additionally,glucagon-like peptide-1 receptor agonists are being actively investigated for their potential benefits,particularly in MASLD.A comprehensive,patient-centered approach that combines metabolic and cardiova-scular care is essential for improving outcomes in patients with HFpEF and MASLD,addressing the global metabolic health challenges.
基金funded by the Science Foundation Ireland(BiOrbic,Dublin,Ireland)and Adesco Nutricines(Dungarvan,Waterford,Ireland)under grant number 16/RC/3889。
文摘Background Organic acids(OA)and maternal nutritional strategies have been demonstrated to promote piglet health and development.The objective of this study was to investigate the effects of incorporating OA-preserved cereal grains into sow diets during late gestation and lactation,aiming to reduce the metabolic demands of lactation while optimising offspring development and growth until slaughter.The experiment compared OA-preserved wheat and barley to conventionally dried grains,focusing on sow and offspring performance,as well as their faecal microbiota during lactation.Forty sows were blocked based on parity,body weight and back fat thickness on d 100 of gestation and assigned to one of two diets:a dried grain lactation diet and a preserved grain lactation diet.Sow faecal samples were collected at farrowing for the coefficient of apparent total tract digestibility(CATTD)of nutrients and microbial analysis.Offspring faecal samples were collected on d 10 postpartum and at weaning(d 26 postpartum)for microbial analysis.Results Sow body weight,back fat changes,gestation and lactation length,total piglets born,wean-to-oestrus interval,and lactation efficiency were unaffected by sow diet(P>0.05).However,sows offered the preserved grain diet exhibited improved CATTD of dry matter,nitrogen,gross energy,and neutral detergent fibre(P<0.05).While no maternal effect was observed on offspring growth during lactation(P>0.05),pigs from sows offered the preserved grain diet showed improved growth and feed efficiency from weaning until slaughter(d 168)compared to those from sows offered the dried grain diet(P<0.05).The preserved grain diet also reduced the abundance of Proteobacteria in sow faeces at farrowing and in their offspring on d 10 postpartum,and improved piglet faecal scores throughout lactation(P=0.05).At weaning,piglets from sows offered the preserved grain diet exhibited an increased abundance of Lactobacillus and reduced abundance of Alistipes in their faeces(P<0.05).Conclusion OA-preserved grains enhanced the CATTD of nutrients in sows,promoted healthier piglet faecal scores during lactation,and improved offspring growth performance post-weaning,potentially linked to beneficial changes observed in the faecal microbiota of sows and their offspring during lactation.
基金National Natural Science Foundation of China,No.81873887National Natural Science Foundation of China Youth Project,No.82101981Shanghai Jiao Tong University School of Medicine Double Hundred Outstanding Person Project,No.20191904。
文摘BACKGROUND Obesity has become a serious public health issue,significantly elevating the risk of various complications.It is a well-established contributor to Heart failure with preserved ejection fraction(HFpEF).Evaluating HFpEF in obesity is crucial.Epicardial adipose tissue(EAT)has emerged as a valuable tool for validating prognostic biomarkers and guiding treatment targets.Hence,assessing EAT is of paramount importance.Cardiovascular magnetic resonance(CMR)imaging is acknowledged as the gold standard for analyzing cardiac function and mor-phology.We hope to use CMR to assess EAT as a bioimaging marker to evaluate HFpEF in obese patients.AIM To assess the diagnostic utility of CMR for evaluating heart failure with preserved ejection fraction[HFpEF;left ventricular(LV)ejection fraction≥50%]by measuring the epicardial adipose tissue(EAT)volumes and EAT mass in obese patients.METHODS Sixty-two obese patients were divided into two groups for a case-control study based on whether or not they had heart failure with HFpEF.The two groups were defined as HFpEF+and HFpEF-.LV geometry,global systolic function,EAT volumes and EAT mass of all subjects were obtained using cine magnetic resonance sequences.RESULTS Forty-five patients of HFpEF-group and seventeen patients of HFpEF+group were included.LV mass index(g/m2)of HFpEF+group was higher than HFpEF-group(P<0.05).In HFpEF+group,EAT volumes,EAT volume index,EAT mass,EAT mass index and the ratio of EAT/[left atrial(LA)left-right(LR)diameter]were higher compared to HFpEF-group(P<0.05).In multivariate analysis,Higher EAT/LA LR diameter ratio was associated with higher odds ratio of HFpEF.CONCLUSION EAT/LA LR diameter ratio is highly associated with HFpEF in obese patients.It is plausible that there may be utility in CMR for assessing obese patients for HFpEF using EAT/LA LR diameter ratio as a diagnostic biomarker.Further prospective studies,are needed to validate these proof-of-concept findings.
基金supported by National Natural Science Foundation of China (Nos. 51827901, 52104096)the Shenzhen National Science Fund for Distinguished Young Scholars (No. RCJC20210706091948015)+2 种基金Open Fund of State Key Laboratory of Hydraulics and Mountain River Engineering, Sichuan University (No. SKHL2216)National Key R & D Program of China (No. 2022YFB3706605)Youth Foundation of Sichuan Natural Science Foundation (No. 2023NSFSC0780)。
文摘Using pressure-preserved coring technique to determine in-situ gas content provides a more precise assessment of gas resource reserves and safeguard of mining safety in coal seams. How coring technique and depth affect the determination of gas content is unclear due to borehole zoning rupture caused by roadway excavation and drilling disturbance. To this end, a proposed coupling model of stress distribution and gas migration was simulated and validated by FLAC^(3D) and COMSOL Multiphysics considering superposition effects of roadway excavation and drilling disturbance. The findings indicate that the roadway surrounding rock displays distinct zoning features including stress relief zone, stress concentration zone that is composed of plastic zone, elastic zone, and original stress zone;and the broken situations depending on the borehole peeping are consistent with the corresponding simulation results.On this basis, this study proposes a set of drilling coring depth calculation and prediction model for the gas desorption affected area under engineering disturbance. Optimal depth of coring drilling is not only approach to the in-situ coal bulk, but also can get the balance of the drilling workload and cost controlling. According to the typical mine site geological conditions and the numerical simulation results in this study, if the roadway excavation time is ~1 year, it is recommended that the pressure-preserved coring depth should be greater than 17 m.
文摘In heart failure with preserved ejection fraction,significant left ventricular diastolic abnormalities are present,despite a normal systolic ejection fraction.This article will consider whether this is consistent with the law of conservation of energy,also know as the first law of thermodynamics.
文摘Heart failure (HF) is a chronic condition characterized by the heart’s inability to pump blood effectively. Hypertension is a frequent contributing factor. The reduced cardiac output leads to fluid accumulation, causing respiratory distress and chest pain. Ejection fraction (EF), a measure of the left ventricle’s pumping capacity, is crucial in HF diagnosis. HF with reduced EF (HFrEF) is defined by an EF below 40%, often caused by coronary artery disease—approximately half of all HF patients present with HFrEF. The remaining cases encompass HF with mid-range EF (40% - 50%) or HF with preserved EF (HFpEF, EF ≥ 50%).
基金supported by the National Natural Science Foundation of China(82274313)Key R&D Program of Shaanxi Province(2023GHZD43)the National Natural Science Foundation of China(81870284).
文摘Background:Formononetin(FMN)has beneficial effects in cardiovascular diseases but its functions and mechanisms in heart failure with preserved ejection fraction(HFpEF)remain unclear.This study aimed at determining whether FMN ameliorated HFpEF-induced cardiac dysfunction and exploring its underlying mechanisms.Methods:The mouse model of HFpEF was established through uninephrectomy surgery and d-aldosterone infusion in C57BL/6 mice.Cardiac remodeling and potential mechanisms of FMN in HFpEF were assessed by histological analysis,immunofluorescence,echocardiography,real-time PCR and western blotting sequentially.Results:FMN prevented myocardial dysfunction,fibrosis and cardiomyocyte apoptosis.The mRNA levels of left ventricular hypertrophy markers were increased in HFpEF mice but they remained unchanged in FMN-treated mice.In addition,the expression levels of PPARαand PGC-1 were increased in HFpEF mice for FMN treatment.The PPARα-PGC-1 complex affected the expression of fatty acid content and encoded enzymes in glucose metabolism.Both the hypertrophy and metabolic impairment due to FMN in HFpEF mice were alleviated after the addition of PPARαantagonist GW6471.Conclusion:In conclusion,FMN could prevent the cardiac hypertrophy in HFpEF mice by activating the PPARα/PGC-1 pathway and regulating energy metabolism,which provides a new therapeutic strategy for HFpEF patients.
文摘With the prevalence of the Internet of Things(IoT)systems,smart cities comprise complex networks,including sensors,actuators,appliances,and cyber services.The complexity and heterogeneity of smart cities have become vulnerable to sophisticated cyber-attacks,especially privacy-related attacks such as inference and data poisoning ones.Federated Learning(FL)has been regarded as a hopeful method to enable distributed learning with privacypreserved intelligence in IoT applications.Even though the significance of developing privacy-preserving FL has drawn as a great research interest,the current research only concentrates on FL with independent identically distributed(i.i.d)data and few studies have addressed the non-i.i.d setting.FL is known to be vulnerable to Generative Adversarial Network(GAN)attacks,where an adversary can presume to act as a contributor participating in the training process to acquire the private data of other contributors.This paper proposes an innovative Privacy Protection-based Federated Deep Learning(PP-FDL)framework,which accomplishes data protection against privacy-related GAN attacks,along with high classification rates from non-i.i.d data.PP-FDL is designed to enable fog nodes to cooperate to train the FDL model in a way that ensures contributors have no access to the data of each other,where class probabilities are protected utilizing a private identifier generated for each class.The PP-FDL framework is evaluated for image classification using simple convolutional networks which are trained using MNIST and CIFAR-10 datasets.The empirical results have revealed that PF-DFL can achieve data protection and the framework outperforms the other three state-of-the-art models with 3%–8%as accuracy improvements.
基金supported by the National 863 Program(Grant No.2006AA06Z206)the National 973 Program(Grant No.2007CB209605)CNPC geophysical laboratories and Ph.D innovative funding in China University of Petroleum(East China)
文摘Traditional pre-stack depth migration can only provide subsurface structural information. However, simple structure information is insufficient for petroleum exploration which also needs amplitude information proportional to reflection coefficients. In recent years, pre-stack depth migration algorithms which preserve amplitudes and based on the one- way wave equation have been developed. Using the method in the shot domain requires a deconvolution imaging condition which produces some instability in areas with complicated structure and dramatic lateral variation in velocity. Depth migration with preserved amplitude based on the angle domain can overcome the instability of the one-way wave migration imaging condition with preserved amplitude. It can also offer provide velocity analysis in the angle domain of common imaging point gathers. In this paper, based on the foundation of the one-way wave continuation operator with preserved amplitude, we realized the preserved amplitude prestack depth migration in the angle domain. Models and real data validate the accuracy of the method.
基金supported by the Program for Guangdong Introducing Innovative and Enterpreneurial Teams(No.2019ZT08G315)National Natural Science Foundation of China(No.51827901,U2013603,and 52004166)。
文摘As shallow resources are increasingly depleted,the mechanics'theory and testing technology of deep insitu rock has become urgent.Traditional coring technologies obtain rock samples without retaining the in-situ environmental conditions,leading to distortion of the measured parameters.Herein,a coring and testing systems retaining in-situ geological conditions is presented:the coring system that obtains in-situ rock samples,and the transfer and testing system that stores and analyzes the rocks under a reconstructed environment.The ICP-Coring system mainly consists of the pressure controller,active insulated core reactor and insulation layer and sealing film.The ultimate bearing strength of 100 MPa for pressurepreservation,temperature control accuracy of 0.97%for temperature-retained are realized.CH_(4)and CO permeability of the optimized sealing film are as low as 3.85 and 0.33 ppm/min.The average tensile elongation of the film is 152.4%and the light transmittance is reduced to 0%.Additionally,the pressure and steady-state temperature accuracy for reconstructing the in-situ environment of transfer and storage system up to 1%and±0.2 is achieved.The error recorded of the noncontact sensor ring made of lowdensity polymer is less than 6%than that of the contact test.The system can provide technical support for the deep in-situ rock mechanics research,improving deep resource acquisition capabilities and further clarifying deep-earth processes.
基金Supported by The European Union,Biomar Ca RE,No.HEALTH-2011-278913
文摘micro RNAs(mi RNAs) are powerful regulators of posttranscriptional gene expression and play an important role in pathophysiological processes. Circulating mi RNAs can be quantified in body liquids and are promising biomarkers in numerous diseases. In cardiovascular disease mi RNAs have been proven to be reliable diagnostic biomarkers for different disease entities. In cardiac fibrosis(CF) and heart failure(HF) dysregulated circulating mi RNAs have been identified,indicating their promising applicability as diagnostic biomarkers. Some mi RNAs were successfully tested in risk stratification of HF implementing their potential use as prognostic biomarkers. In this respect mi RNAs might soon be implemented in diagnostic clinical routine. In the young field of mi RNA based research advances have been made in identifying mi RNAs as potential targets for the treatment of experimental CF and HF. Promising study results suggest their potential future application as therapeutic agents in treatment of cardiovascular disease. This article summarizes the current state of the various aspects of mi RNA research in the field of CF and HF with reduced ejection fraction as well as preserved ejection fraction. The review provides an overview of the application of circulating mi RNAs as biomarkers in CF and HF and current approaches to therapeutically utilize mi RNAs in this field of cardiovascular disease.
基金financially supported by the Chinese National Natural Science Funds (31772043)the Fundamental Research Funds for the Central Universities (2662018JC021)
文摘Traditional Chinese preserved egg products have exhibited some anti-inflammatory effects,but their mechanisms of action remain unknown.This study aimed to investigate the anti-inflammatory effects of preserved egg white(PEW)treatment on dextran sulfate sodium(DSS)-induced colitis in mice and the underlying mechanisms.The results showed that treatment with PEW in mice with DSS-induced colitis for 14 days effectively improved the clinical signs,inhibited the secretion and gene expression of pro-inflammatory cytokines,and reduced myeloperoxidase(MPO)activity and oxidative stress levels.In addition,western blotting results showed that PEW significantly suppressed DSS-induced phosphorylation levels of nuclear factor-kappa B(NF-κB)p65 and p38 mitogen-activated protein kinase(MAPK)in colon tissues of mice with colitis.PEW also enhanced the production of short-chain fatty acids(SCFAs)and modulated gut microbiota composition in mice with DSS-induced colitis,including increasing the relative abundance of beneficial bacteria Lachnospiraceae,Ruminococcaceae and Muribaculaceae,and reducing the relative abundance of harmful bacteria Proteobacteria.Taken together,our study demonstrated that preserved egg white could alleviate DSS-induced colitis in mice through the reduction of oxidative stress,modulation of inflammatory cytokines,NF-κB,MAPK and gut microbiota composition.
文摘Heart failure with preserved ejection fraction(HFPEF)is common and represents a major challenge in cardiovascular medicine.Most of the current treatment of HFPEF is based on morbidity benefits and symptom reduction.Various pharmacological interventions available for heart failure with reduced ejection fraction have not been supported by clinical studies for HFPEF.Addressing the specific aetiology and aggressive risk factor modification remain the mainstay in the treatment of HFPEF.We present a brief overview of the currently recommended therapeutic options with available evidence.
基金supported by the he National Natural Science Foundation of China (No. 81770441, No. 81700398, No. 81970309)Nanjing Municipal Healthcare Grant YKK16127
文摘Background Endogenous aldehyde damages DNA and potentiates an ageing phenotype. The aldehyde dehydrogenase 2(ALDH2) rs671 polymorphism has a prevalence of 30%–50% in Asian populations. In this study, we aimed to analyze risk factors contributing to the development of heart failure with preserved ejection fraction(HFpEF) along with the genetic exposure in Chinese patients hospitalized with cardiovascular diseases(CVD). Methods From July 2017 to October 2018, a total of 770 consecutive Chinese patients with normal left ventricular ejection fractions(LVEF) and established CVD(hypertension, coronary heart diseases, or diabetes) were enrolled in this prospective cross-sectional study. HFpEF was defined by the presence of at least one of symptom(dyspnoea and fatigue) or sign(rales and ankle swelling) related to heart failure;N-terminal pro-B-Type natriuretic peptide(NT pro-BNP ≥ 280 pg/mL);LVEF ≥ 50%;and at least one criterion related to elevated ventricular filling pressure or diastolic dysfunction(left atrial diameter > 40 mm, E/E’ ≥ 13, E’/A’ < 1 or concurrent atrial fibrillation). Logistic regression was performed to yield adjusted odds ratios(ORs) for HFp EF incidence associated with traditional and/or genetic exposures. Results Finally, among 770 patients with CVD, 92(11.9%) patients were classified into the HFpEF group according to the diagnostic criteria. The mean age of the participants was 67 ± 12 years, and 278(36.1%) patients were females. A total of 303(39.4%) patients were ALDH2*2 variant carriers. In the univariate analysis, eight exposures were found to be associated with HFpEF: atrial fibrillation, ALDH2*2 variants, hypertension, age, anaemia, smoking, alcohol consumption and sex. Multivariable logistic regression showed that 4 ‘A’ variables(atrial fibrillation, ALDH2*2 variants, age and anaemia) were significantly associated with an increased risk of HFpEF. Atrial fibrillation was associated with a 3.8-fold increased HFpEF risk(95% CI: 2.21–6.61, P < 0.001), and the other three exposures associated with increased HFpEF risk were the ALDH2*2 variant(OR = 2.41, 95% CI: 1.49–3.87, P < 0.001), age(OR = 2.14, 95% CI: 1.27–3.60, P = 0.004), and anaemia(OR = 1.79, 95% CI: 1.05–3.03, P = 0.032). These four variables predicted HFpEF incidence in Chinese CVD patients(C-statistic = 0.745, 95% CI: 0.691–0.800, P < 0.001). Conclusions 4 A traits(atrial fibrillation, ALDH2*2 variants, age and anaemia) were associated with an increased risk of HFpEF in Chinese CVD patients. Our results provide potential clues to the aetiology, pathophysiology and therapeutic targets of HFpEF.
文摘Heart failure(HF) is the leading cause of hospitalization among older adults and the prevalence is growing with the aging populations in the Western countries. Epidemiologic reports suggest that approximately 50% of patients who have signs or symptoms of HF have preserved left ventricular ejection fraction. This HF type predominantly affects women and the elderly with other co-morbidities, such as diabetes, hypertension, and overt volume status. Most of the current treatment strategies are based on morbidity benefits such as quality of life and reduction of clinical HF symptoms. Treatment of patients with HF with preserved ejection fraction displayed disappointing results from several large randomized controlled trials. The heterogeneity of HF with preserved ejection fraction, understood as complex syndrome, seems to be one of the primary reasons. Here, we present an overview of the current management strategies with available evidence and new therapeutic approach from drugs currently in clinical trials, which target diastolic dysfunction, chronotropic incompetence, and risk factor management. We provide an outline and interpretation of recent clinical trials that failed to improve outcome and survival in patients with HF with preserved ejection fraction.
文摘Objective To determine the effect of the phosphodiesterase-5 inhibitor sildenafil compared with placebo on exercise capacity and clinical status in HFPEF. Design Multicenter, double-blind, placebo-controlled, parallel-group, randomized clinical trial of 216 sta- ble outpatients with HF, ejection fraction ≥ 50%, elevated N-terminal brain-type natriuretic peptide or elevat- ed invasively measured filling pressures, and reduced exercise capacity. Participants were randomized from October 2008 through February 2012 at 26 centers in North America. Follow-up was through August 30, 2012.
文摘With the launch of sacubitril/valsartan(ARNI),there are new options for the treatment of heart failure(HF).However,ARNI is currently only used in HF patients with reduced ejection fraction(HFrEF).No evidence shows that no modern treatment can reduce mortality in HF patients with preserved ejection fraction(HFpEF).Therefore,it is urgently necessary clarify whether ARNI can be used in the treatment of HFpEF.In the present study,we summarized the research progress of ARNI in the treatment of HFpEF.
基金supported by the National Natural Science Foundation of China ( 11732001)
文摘Objective Heart failure(HF)is divided into two types:Heart failure with reduced ejection fraction(HFrEF)and heart failure with preserved ejection fraction(HFpEF).The latter always results in diastolic dysfunction,characterized by changes in mechanical properties.The objective of this study is to build a finite element(FE)model of HFpEF and analyze diastolic and systolic function in rats.Methods Ten Dahl salt-sensitive rats were fed either a low-salt(LS)(n=5)or highsalt(HS)(n=5)diet beginning at 7 weeks of age and scanned by ultrasonic machine at 14 weeks of age.A non-linear FE model of the left ventricle(LV)was built from cardiac echo images at end-diastole and passive material properties of the LV were prescribed using Fung’s transversely isotropic constitutive law.Fiber angles of the endocardium and epicardium were prescribed as 53°°and-52°,respectively,with respect to the circumferential direction and varied linearly through the LV wall.The method developed by Krishnamurthywas used to determine the unloaded geometry to estimate the Fung passive material parameters.LV end-diastolic pressure(EDP)was determined from the measured pressure waves and applied to the endocardium at the unloaded geometry to simulate passive filling.Active material properties of the LV were prescribed using Guccione’s time-varying elastance model and maximum isometric tension was scaled to match the measured peak systolic pressure.The finite element model was then coupled to the Windkessel model,whose parameters were adjusted to the measured hemodynamics.Results Measured LVEDPs of LS and HS rats were 4.9±3.4 mmHg and 13.2±5.4 mmHg(P-0.030 8),respectively.End-diastolic Cauchy stress along the fiber direction for LS rats was significantly lower than for HS rats(0.91±0.60 kPa vs 3.00±0.63 kPa,P=0.001 4)and there was a similar trend in end-diastolic Green Strain along the fiber direction(0.058±0.003 vs 0.072±0.010,P=0.012 8,Figure 1b),as well.There was no distinctive difference between end-systolic Cauchy stress along the fiber direction for LS rats and HS rats(17.2±4.3 kPa vs 17.2±5.5 kPa,P=0.991 9)but end-systolic Green Strain along the fiber direction for LS rats was significantly higher than for HS rats(-0. 108±0.017 vs-0.065±0.024,negative sign represents direction).Conclusions For rats with HFpEF,it is the elevated LVEDP that induces the increase in end-diastolic stress and strain,thereby leading to diastolic dysfunction.Because of the preserved ejection fraction,HFpEF has less effect on systolic function.
文摘Heart failure with preserved ejection fraction(HFpEF)is a heterogeneous syndrome with various comorbidities,multiple cardiac and extracardiac pathophysiologic abnormalities,and diverse phenotypic presentations.Since HFpEF is a heterogeneous disease with different phenotypes,individualized treatment is required.HFpEF with type 2 diabetes mellitus(T2DM)represents a specific phenotype of HFpEF,with about 45%-50% of HFpEF patients suffering from T2DM.Systemic inflammation associated with dysregulated glucose metabolism is a critical pathological mechanism of HFpEF with T2DM,which is intimately related to the expansion and dysfunction(inflammation and hypermetabolic activity)of epicardial adipose tissue(EAT).EAT is well established as a very active endocrine organ that can regulate the pathophysiological processes of HFpEF with T2DM through the paracrine and endocrine mechanisms.Therefore,suppressing abnormal EAT expansion may be a promising therapeutic strategy for HFpEF with T2DM.Although there is no treatment specifically for EAT,lifestyle management,bariatric surgery,and some pharmaceutical interventions(anti-cytokine drugs,statins,proprotein convertase subtilisin/kexin type 9 inhibitors,metformin,glucagon-like peptide-1 receptor agonists,and especially sodium-glucose cotransporter-2 inhibitors)have been shown to attenuate the inflammatory response or expansion of EAT.Importantly,these treatments may be beneficial in improving the clinical symptoms or prognosis of patients with HFpEF.Accordingly,well-designed randomized controlled trials are needed to validate the efficacy of current therapies.In addition,more novel and effective therapies targeting EAT are needed in the future.
