Accurately evaluating the quality and scale of deep oil and gas reservoirs is the key to effectively exploring and developing deep oil and gas resources.Changes in temperature and pressure can cause significant variat...Accurately evaluating the quality and scale of deep oil and gas reservoirs is the key to effectively exploring and developing deep oil and gas resources.Changes in temperature and pressure can cause significant variations in key reservoir quality para meters,such as porosity,permeability,and satu ration,leading to distortions in oil and gas reserve assessments.To addresses the technical bottleneck of the existing pressu re-preserved coring systems,which has a pressure-preserved ca pacity not exceed 70 MPa due to the limitations of small coring space,a complex coring environment,significant disturbance during the coring process,and the difficulty in controlling coring operations,a self-sealing control principle and method for pressure-preserved coring was proposed.The sealing structural parameters of the pressure-preserved controller(PPC) under high temperature(150℃) were optimized through experiments and numerical simulations,the sealing failure mechanism was thoroughly revealed,and the pressure-preserved capacity of the PPC under high temperature was enhanced from 100 to 140 MPa.In addition,to achieve the temperature preservation of the core in the deep oil and gas environment,a temperature preservation system combining active and passive temperature preservation was designed and integrated into the deep oil and gas in-situ temperature pressure preserved(ITPP) coring system.Finally,the coring function and temperature pressure preserved capacity of the ITPP coring system were verified through field and laboratory tests.The results show that the developed ITPP coring system can successfully achieve the temperature pressure preserved function,and can sample oil and gas-bearing core samples with a diameter of 50 mm and a maximum length of 1000 mm from wells up to 5000 m.This study addresses the urgent need for reliable and effective pressure-preservation in deep oil and gas exploration.展开更多
BACKGROUND Heart failure with preserved ejection fraction(HFpEF)accounts for approximately half of heart failure cases and is associated with high morbidity and mortality.Beta-blockers(BB)and calcium channel blockers(...BACKGROUND Heart failure with preserved ejection fraction(HFpEF)accounts for approximately half of heart failure cases and is associated with high morbidity and mortality.Beta-blockers(BB)and calcium channel blockers(CCB)are commonly used for symptom control and comorbidity management,but their comparative effectiveness and safety remain unclear.AIM To compare the effectiveness and safety of BB vs CCB in patients with HFpEF using simulated real-world data and propensity score-matched analyses.METHODS Simulated data for 4000 HFpEF patients(2000 BB,2000 CCB)were generated based on distributions extracted from electronic medical records spanning 2014-2023.Inclusion criteria included adults with left ventricular ejection fraction≥50%and initiation of BB or CCB.Effectiveness outcomes encompassed mortality,heart failure hospitalizations,and changes in clinical parameters.Safety outcomes included bradycardia,hypotension,and drug discontinuation.Statistical analyses used t-tests,χ2 tests,Cox proportional hazards models for hazard ratios(HR),and incidence rate ratios(IRR)in R software.Propensity score matching(PSM)was performed to balance baseline characteristics,with outcomes reassessed in the matched cohort.RESULTS Baseline characteristics were largely balanced,with minor differences in sex,chronic kidney disease,systolic blood pressure,and left atrial volume index.BB demonstrated lower all-cause mortality(crude HR 0.78,95%CI:0.70-0.87,P=0.003),heart failure hospitalization(crude HR 0.86,95%CI:0.77-0.96,P=0.031),and composite endpoint(crude HR 0.85,95%CI:0.79-0.91,P<0.001)rates compared to CCB.IRR for heart failure hospitalizations and emergency visits favored BB.Safety profiles showed higher symptomatic bradycardia(9.2%vs 4.9%,P<0.001)and drug discontinuation(11.3%vs 9.3%,P=0.043)with BB,and higher hypotension(7.2%vs 11.5%,P<0.001)with CCB.Matched analyses showed all-cause mortality rates of 0.0622 per person-year for BB vs 0.0649 for CCB(HR 0.96,95%CI:0.85-1.08),heart failure hospitalization rates of 0.0751 vs 0.0888(HR 0.84,95%CI:0.75-0.94),and IRR for number of heart failure hospitalizations of 1.65 for CCB vs BB(95%CI:1.51-1.80,P<0.001).CONCLUSION BB may offer potential advantages in reducing mortality and hospitalizations in HFpEF compared to CCB,with distinct safety considerations.PSM confirmed these trends with reduced confounding.Personalized therapy is recommended,warranting prospective trials for validation.展开更多
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
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
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
Since the launch of a digitization project for the protection and utilization of ancient texts in the Sakya Monastery of the Xizang Autonomous Region in 2012,significant efforts and achievements have been made in anci...Since the launch of a digitization project for the protection and utilization of ancient texts in the Sakya Monastery of the Xizang Autonomous Region in 2012,significant efforts and achievements have been made in ancient text preservation.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
Tibetan spruce (Picea smithiana) is an endemic species of the Himalayas,and it distributes only in a re-stricted area with very low number.To address the lack of detailed distributional information,we used maximum en-...Tibetan spruce (Picea smithiana) is an endemic species of the Himalayas,and it distributes only in a re-stricted area with very low number.To address the lack of detailed distributional information,we used maximum en-tropy (Maxent) niche-based model to predict the species' potential distribution from limited occurrence-only records.The location data of P.smithiana,relative bioclimatic variables,vegetation data,digital elevation model (DEM),and the derived data were analyzed in Maxent.The receiver operating characteristic (ROC) curve was applied to assess the prediction accuracy.The Maxent jackknife test was performed to quantify the training gains from data layers and the response of P.smithiana distribution to four typical environmental variables was analyzed.Results show that the model performs well at the regional scale.There is a potential for continued expansion of P.smithiana population numbers and distribution in China.P.smithiana potentially distributes in the lower reaches of Gyirong Zangbo and Poiqu rivers in Gyirong and Nyalam counties in Qomolangma (Mount Everest) National Nature Preserve (QNNP),China.The species prefers warm temperate climate in mountain area and mainly distributes in needle-leaved evergreen closed to open forest and mixed forest along the river valley at relatively low altitudes of about 2000-3000 m.Model simulations suggest that distribution patterns of rare species with few species numbers can be well predicted by Max-ent.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
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
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
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
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
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
OBJECTIVE: To determine whether Shunxin decoction(顺心组方) improves diastolic function in rats with heart failure with preserved ejection fraction(HFp EF) by regulating the cyclic guanosine monophosphatedependent pro...OBJECTIVE: To determine whether Shunxin decoction(顺心组方) improves diastolic function in rats with heart failure with preserved ejection fraction(HFp EF) by regulating the cyclic guanosine monophosphatedependent protein kinase(c GMP-PKG) signaling pathway. METHODS: Except for control group 8 and sham surgery group 8, the remaining 32 male Sprague-Dawlay rats were developed into HFp EF rat models using the abdominal aorta constriction method. These rats in the HFp EF model were randomly divided into the model group, the Shunxin high-dose group, the Shunxin lowdose group, and the Qiliqiangxin capsule group. The three groups received high-dose Shunxin decoction, lowdose Shunxin decoction, and Qiliqiangxin capsule by gavage, respectively, for 14 d. After the intervention, the diastolic function of each rat was evaluated by testing E/A, heart index, hematoxylin-eosin staining, Masson, myocardial ultrastructure, and N-terminal pro-brain natriuretic peptide(NT-pro BNP). The Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine(BATMAN-TCM) software was used to predict targets for which Shunxin decoction acts on the c GMP-PKG pathway. Natriuretic peptide receptor A(NPRA) and guanylate cyclase(GC) were detected by immunohistochemistry, and e NOS, phosphodiesterase 5A(PDE5A), and c GMP-dependent protein kinase 1(PKG I) were determined by Western blotting. RESULTS: Compared to the model group, the thickness of the interventricular septum at the end of diastole(IVSd) and the thickness of the posterior wall at the end of diastole(PWd) of the Shunxin decoction high-dose group, Shunxin decoction low-dose group, and Qiliqiangxin capsule group were all significantly reduced(P < 0.01). Furthermore, Shunxin decoction high-dose group E/A value was decreased(P < 0.01). Compared to the model group, the expression of NPRA and GC increased in the Shunxin decoction low-dose group and the Qiliqiangxin capsule group(P < 0.01). Compared to the model group, the expressions of e NOS and PKG I increased(P < 0.05) in the Shunxin decoction high-dose group. The expression of PDE5A expression decreased in the myocardium of the Shunxin decoction high-dose group, Shunxin decoction low-dose group, and Qiliqiangxin capsule group compared to the model group(P < 0.01). CONCLUSIONS: Shunxin decoction can improve diastolic function in rats with HFp EF. It increases the expression of NPRA, GC, and e NOS in the myocardial cell c GMP-PKG signaling pathway, upregulates c GMP expression, decreases PDE5A expression to reduce the c GMP degradation. Thus, the c GMP continually stimulates PKG I, reversing myocardial hypertrophy and improving myocardial compliance in HFp EF rats.展开更多
基金supported by the National Natural Science Foundation of China(Grant Nos.524B2040,2023M742460,and 52304146)。
文摘Accurately evaluating the quality and scale of deep oil and gas reservoirs is the key to effectively exploring and developing deep oil and gas resources.Changes in temperature and pressure can cause significant variations in key reservoir quality para meters,such as porosity,permeability,and satu ration,leading to distortions in oil and gas reserve assessments.To addresses the technical bottleneck of the existing pressu re-preserved coring systems,which has a pressure-preserved ca pacity not exceed 70 MPa due to the limitations of small coring space,a complex coring environment,significant disturbance during the coring process,and the difficulty in controlling coring operations,a self-sealing control principle and method for pressure-preserved coring was proposed.The sealing structural parameters of the pressure-preserved controller(PPC) under high temperature(150℃) were optimized through experiments and numerical simulations,the sealing failure mechanism was thoroughly revealed,and the pressure-preserved capacity of the PPC under high temperature was enhanced from 100 to 140 MPa.In addition,to achieve the temperature preservation of the core in the deep oil and gas environment,a temperature preservation system combining active and passive temperature preservation was designed and integrated into the deep oil and gas in-situ temperature pressure preserved(ITPP) coring system.Finally,the coring function and temperature pressure preserved capacity of the ITPP coring system were verified through field and laboratory tests.The results show that the developed ITPP coring system can successfully achieve the temperature pressure preserved function,and can sample oil and gas-bearing core samples with a diameter of 50 mm and a maximum length of 1000 mm from wells up to 5000 m.This study addresses the urgent need for reliable and effective pressure-preservation in deep oil and gas exploration.
文摘BACKGROUND Heart failure with preserved ejection fraction(HFpEF)accounts for approximately half of heart failure cases and is associated with high morbidity and mortality.Beta-blockers(BB)and calcium channel blockers(CCB)are commonly used for symptom control and comorbidity management,but their comparative effectiveness and safety remain unclear.AIM To compare the effectiveness and safety of BB vs CCB in patients with HFpEF using simulated real-world data and propensity score-matched analyses.METHODS Simulated data for 4000 HFpEF patients(2000 BB,2000 CCB)were generated based on distributions extracted from electronic medical records spanning 2014-2023.Inclusion criteria included adults with left ventricular ejection fraction≥50%and initiation of BB or CCB.Effectiveness outcomes encompassed mortality,heart failure hospitalizations,and changes in clinical parameters.Safety outcomes included bradycardia,hypotension,and drug discontinuation.Statistical analyses used t-tests,χ2 tests,Cox proportional hazards models for hazard ratios(HR),and incidence rate ratios(IRR)in R software.Propensity score matching(PSM)was performed to balance baseline characteristics,with outcomes reassessed in the matched cohort.RESULTS Baseline characteristics were largely balanced,with minor differences in sex,chronic kidney disease,systolic blood pressure,and left atrial volume index.BB demonstrated lower all-cause mortality(crude HR 0.78,95%CI:0.70-0.87,P=0.003),heart failure hospitalization(crude HR 0.86,95%CI:0.77-0.96,P=0.031),and composite endpoint(crude HR 0.85,95%CI:0.79-0.91,P<0.001)rates compared to CCB.IRR for heart failure hospitalizations and emergency visits favored BB.Safety profiles showed higher symptomatic bradycardia(9.2%vs 4.9%,P<0.001)and drug discontinuation(11.3%vs 9.3%,P=0.043)with BB,and higher hypotension(7.2%vs 11.5%,P<0.001)with CCB.Matched analyses showed all-cause mortality rates of 0.0622 per person-year for BB vs 0.0649 for CCB(HR 0.96,95%CI:0.85-1.08),heart failure hospitalization rates of 0.0751 vs 0.0888(HR 0.84,95%CI:0.75-0.94),and IRR for number of heart failure hospitalizations of 1.65 for CCB vs BB(95%CI:1.51-1.80,P<0.001).CONCLUSION BB may offer potential advantages in reducing mortality and hospitalizations in HFpEF compared to CCB,with distinct safety considerations.PSM confirmed these trends with reduced confounding.Personalized therapy is recommended,warranting prospective trials for validation.
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.
文摘Since the launch of a digitization project for the protection and utilization of ancient texts in the Sakya Monastery of the Xizang Autonomous Region in 2012,significant efforts and achievements have been made in ancient text preservation.
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Under the auspices of National Basic Research Program of China (No.2010CB951704)Institutional Consolidation for Coordinated and Integrated Monitoring of Natural Resources towards Sustainable Development and Environmental Conservation in the Hindu Kush-Karakoram-Himalaya Mountain Complex (No.76444-000)External Cooperation Program of Chinese Academy of Sciences (No.GJHZ0954)
文摘Tibetan spruce (Picea smithiana) is an endemic species of the Himalayas,and it distributes only in a re-stricted area with very low number.To address the lack of detailed distributional information,we used maximum en-tropy (Maxent) niche-based model to predict the species' potential distribution from limited occurrence-only records.The location data of P.smithiana,relative bioclimatic variables,vegetation data,digital elevation model (DEM),and the derived data were analyzed in Maxent.The receiver operating characteristic (ROC) curve was applied to assess the prediction accuracy.The Maxent jackknife test was performed to quantify the training gains from data layers and the response of P.smithiana distribution to four typical environmental variables was analyzed.Results show that the model performs well at the regional scale.There is a potential for continued expansion of P.smithiana population numbers and distribution in China.P.smithiana potentially distributes in the lower reaches of Gyirong Zangbo and Poiqu rivers in Gyirong and Nyalam counties in Qomolangma (Mount Everest) National Nature Preserve (QNNP),China.The species prefers warm temperate climate in mountain area and mainly distributes in needle-leaved evergreen closed to open forest and mixed forest along the river valley at relatively low altitudes of about 2000-3000 m.Model simulations suggest that distribution patterns of rare species with few species numbers can be well predicted by Max-ent.
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.
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.
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.
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.
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.
基金Supported by Lanzhou Science and Technology Planning Project:Study on a New Traditional Chinese Herb Preparation for Treating HFp EF (No. 2017-4-125)Belt and Road Special Project of Lanzhou University:Study on Countermeasures of Gansu Traditional Chinese Medicine Industry Entering Five Central Asian Countries (No. 2018ldbrzd004)。
文摘OBJECTIVE: To determine whether Shunxin decoction(顺心组方) improves diastolic function in rats with heart failure with preserved ejection fraction(HFp EF) by regulating the cyclic guanosine monophosphatedependent protein kinase(c GMP-PKG) signaling pathway. METHODS: Except for control group 8 and sham surgery group 8, the remaining 32 male Sprague-Dawlay rats were developed into HFp EF rat models using the abdominal aorta constriction method. These rats in the HFp EF model were randomly divided into the model group, the Shunxin high-dose group, the Shunxin lowdose group, and the Qiliqiangxin capsule group. The three groups received high-dose Shunxin decoction, lowdose Shunxin decoction, and Qiliqiangxin capsule by gavage, respectively, for 14 d. After the intervention, the diastolic function of each rat was evaluated by testing E/A, heart index, hematoxylin-eosin staining, Masson, myocardial ultrastructure, and N-terminal pro-brain natriuretic peptide(NT-pro BNP). The Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine(BATMAN-TCM) software was used to predict targets for which Shunxin decoction acts on the c GMP-PKG pathway. Natriuretic peptide receptor A(NPRA) and guanylate cyclase(GC) were detected by immunohistochemistry, and e NOS, phosphodiesterase 5A(PDE5A), and c GMP-dependent protein kinase 1(PKG I) were determined by Western blotting. RESULTS: Compared to the model group, the thickness of the interventricular septum at the end of diastole(IVSd) and the thickness of the posterior wall at the end of diastole(PWd) of the Shunxin decoction high-dose group, Shunxin decoction low-dose group, and Qiliqiangxin capsule group were all significantly reduced(P < 0.01). Furthermore, Shunxin decoction high-dose group E/A value was decreased(P < 0.01). Compared to the model group, the expression of NPRA and GC increased in the Shunxin decoction low-dose group and the Qiliqiangxin capsule group(P < 0.01). Compared to the model group, the expressions of e NOS and PKG I increased(P < 0.05) in the Shunxin decoction high-dose group. The expression of PDE5A expression decreased in the myocardium of the Shunxin decoction high-dose group, Shunxin decoction low-dose group, and Qiliqiangxin capsule group compared to the model group(P < 0.01). CONCLUSIONS: Shunxin decoction can improve diastolic function in rats with HFp EF. It increases the expression of NPRA, GC, and e NOS in the myocardial cell c GMP-PKG signaling pathway, upregulates c GMP expression, decreases PDE5A expression to reduce the c GMP degradation. Thus, the c GMP continually stimulates PKG I, reversing myocardial hypertrophy and improving myocardial compliance in HFp EF rats.
