Diagnostic performance of intravascular ultrasound-based fractional flow reserve in evaluating of intermediate left main stenosis

BACKGROUND The recently introduced ultrasonic flow ratio(UFR),is a novel fast computational method to derive fractional flow reserve(FFR)from intravascular ultrasound(IVUS)images.In the present study,we evaluate the diagnostic performance of UFR in patients with intermediate left main(LM)stenosis.METHODS This is a prospective,single center study enrolling consecutive patients with presence of intermediated LM lesions(diameter stenosis of 30%-80%by visual estimation)underwent IVUS and FFR measurement.An independent core laboratory assessed offline UFR and IVUS-derived minimal lumen area(MLA)in a blinded fashion.RESULTS Both UFR and FFR were successfully achieved in 41 LM patients(mean age,62.0±9.9 years,46.3%diabetes).An acceptable correlation between UFR and FFR was identified(r=0.688,P<0.0001),with an absolute numerical difference of 0.03(standard difference:0.01).The area under the curve(AUC)in diagnosis of physiologically significant coronary stenosis for UFR was 0.94(95%CI:0.87-1.01),which was significantly higher than angiographic identified stenosis>50%(AUC=0.66,P<0.001)and numerically higher than IVUS-derived MLA(AUC=0.82;P=0.09).Patient level diagnostic accuracy,sensitivity and specificity for UFR to identify FFR≤0.80 was 82.9%(95%CI:70.2-95.7),93.1%(95%CI:82.2-100.0),58.3%(95%CI:26.3-90.4),respectively.CONCLUSION In patients with intermediate LM diseases,UFR was proved to be associated with acceptable correlation and high accuracy with pressure wire-based FFR as standard reference.The present study supports the use of UFR for functional evaluation of intermediate LM stenosis.

The prognostic value of collateral circulation in coronary chronic total occlusion underwent percutaneous coronary intervention

BACKGROUND The prognostic value of coronary collateral circulation(CC)in patients undergoing chronic total occlusion(CTO)percutaneous coronary intervention(PCI)is underdetermined.The purpose of the study was to assess the prognostic value of current two CC grading systems and their association with long-term outcomes in patients with CTO underwent PCI.METHODS We consecutively enrolled patients with single-vessel CTO underwent PCI between January 2010 and December2013.All patients were categorized into well-developed or poor-developed collaterals group according to angiographic Werner's CC(grade 2 vs.grade 0–1)or Rentrop(grade 3 vs.grade 0–2)grading system.The primary endpoint was 5-year cardiac death.RESULTS Of 2452 enrolled patients,the overall technical success rate was 74.1%.Well-developed collaterals were present in686 patients(28.0%)defined by Werner's CC grade 2,and in 1145 patients(46.7%)by Rentrop grade 3.According to Werner's CC grading system,patients with well-developed collaterals had a lower rate of 5-year cardiac death compared with those with poordeveloped collaterals(1.6%vs.3.3%,P=0.02),those with suboptimal recanalization was associated with higher rate of 5-year cardiac death compared with optimal recanalization(4.7%vs.0.8%,P=0.01)and failure patients(4.7%vs.1.6%,P=0.12).However,the similar effect was not shown in Rentrop grading system.CONCLUSIONS In patients with the single-vessel CTO underwent PCI,well-developed collaterals by Werner's CC definition were associated with lower rate of 5-year cardiac death.Werner's CC grading system had a greater prognostic value than Rentrop grading system in patients with CTO underwent PCI.

Association of acute glycemic parameters at admission with cardiovascular mortality in the oldest old with acute myocardial infarction

OBJECTIVES Stress-related glycemic indicators,including admission blood glucose(ABG),stress-hyperglycemia ratio(SHR),and glycemic gap(GG),have been associated with worse outcomes after acute myocardial infarction(AMI).However,data regarding their prognostic value in the oldest old with AMI are unavailable.Therefore,this study aimed to investigate the association of stress-related glycemic indicators with short-and long-term cardiovascular mortality(CVM)in the oldest old(≥80 years)with AMI.METHODS In this prospective study,a total of 933 consecutive old patients with AMI admitted to FuWai hospital(Beijing,China)were enrolled.On admission,ABG,SHR,and GG were assessed and all participants were classified according to their quartiles.Kaplan-Meier,restricted cubic splines(RCS),and multivariate Cox regression analyses were performed to evaluate the association between these glycemic indicators and CVM within 30 days and long-term follow-up.RESULTS During an average of 1954 patient-years of follow-up,a total of 250 cardiovascular deaths were recorded.Kaplan-Meier analyses showed the lowest CVM in quartile 1 of ABG and in quartile 2 of SHR and GG.After adjusting for potential covariates,patients in quartile 4 of ABG,SHR,and GG had a respective 1.67-fold(95%CI:1.03-2.69;P=0.036),1.80-fold(95%CI:1.16-2.79;P=0.009),and 1.78-fold(95%CI:1.14-2.79;P=0.011)higher risk of long-term CVM risk compared to those in the reference groups(quartile 1 of ABG and quartile 2 of SHR and GG).Furthermore,RCS suggested a J-shaped relationship of ABG and a Ushaped association of SHR and GG with long-term CVM.Additionally,we observed similar associations of these acute glycemic parameters with 30-day CVM.CONCLUSIONS Our data first indicated that SHR and GG consistently had a U-shaped association with both 30-day and longterm CVM among the oldest old with AMI,suggesting that they may be useful for risk stratification in this special population.

应急状态下新冠流行曲线预测的方法学研究——基于北京市百度搜索和传统流感样病例监测

Surveillance is an essential work on infectious diseases prevention and control.When the pandemic occurred,the inadequacy of traditional surveillance was exposed,but it also provided a valuable opportunity to explore new surveillance methods.This study aimed to estimate the transmission dynamics and epidemic curve of severe acute respiratory syndrome coronavirus 2(SARS-Co V-2)Omicron BF.7 in Beijing under the emergent situation using Baidu index and influenza-like illness(ILI)surveillance.A novel hybrid model(multiattention bidirectional gated recurrent unit(MABG)-susceptible-exposed-infected-removed(SEIR))was developed,which leveraged a deep learning algorithm(MABG)to scrutinize the past records of ILI occurrences and the Baidu index of diverse symptoms such as fever,pyrexia,cough,sore throat,anti-fever medicine,and runny nose.By considering the current Baidu index and the correlation between ILI cases and coronavirus disease 2019(COVID-19)cases,a transmission dynamics model(SEIR)was formulated to estimate the transmission dynamics and epidemic curve of SARS-Co V-2.During the COVID-19 pandemic,when conventional surveillance measures have been suspended temporarily,cases of ILI can serve as a useful indicator for estimating the epidemiological trends of COVID-19.In the specific case of Beijing,it has been ascertained that cumulative infection attack rate surpass 80.25%(95%confidence interval(95%CI):77.51%-82.99%)since December 17,2022,with the apex of the outbreak projected to transpire on December 12.The culmination of existing patients is expected to occur three days subsequent to this peak.Effective reproduction number(Rt)represents the average number of secondary infections generated from a single infected individual at a specific point in time during an epidemic,remained below 1 since December 17,2022.The traditional disease surveillance systems should be complemented with information from modern surveillance data such as online data sources with advanced technical support.Modern surveillance channels should be used primarily in emerging infectious and disease outbreaks.Syndrome surveillance on COVID-19 should be established to following on the epidemic,clinical severity,and medical resource demand.

Invasive versus conservative strategy in consecutive patients aged 80 years or older with non-ST-segment elevation myocardial infarction: a retrospective study in China

Objective To investigate whether the very elderly patients with non-ST-segment elevation myocardial infarction (NSTEMI) will benefit from an invasive strategy versus a conservative strategy. Methods 190 consecutive patients aged 80 years or older with NSTEMI were included in the retrospective study from September 2014 to August 2017, of which 69 patients received conservative strategy and 121 patients received invasive strategy. The primary outcome was death. Multivariate Cox regression models were used to assess the statistical association between strategies and mortality. The survival probability was further analyzed. Results The primary outcome occurred in 17.4% patients in the invasive group and in 42.0% patients in the conservative group (P = 0.0002). The readmission rate in the invasive group (14.9%) was higher than that in the conservative group (7.2%). Creatinine level (OR = 1.01, 95% CI: 0.10–1.03, P = 0.05) and use of diuretic (OR = 3.65, 95% CI: 1.56–8.53, P = 0.003) were independent influential factors for invasive strategy. HRs for multivariate Cox regression models were 3.45 (95% CI: 1.77–6.75, P = 0.0003), 3.02 (95% CI: 1.52–6.01, P = 0.0017), 2.93 (95% CI: 1. 46–5.86, P = 0.0024) and 2.47 (95% CI: 1.20–5.07, P = 0.0137). Compared with the patients received invasive strategy, the conservative group had remarkably reduced survival probability with time since treatment (P < 0.001). Conclusions An invasive strategy is superior to a conservative strategy in reducing mortality of patients aged 80 years or older with NSTEMI. Our results suggest that an invasive strategy is more suitable for the very elderly patients with NSTEMI in China.

Research progress on gel polymer electrolytes for lithium-sulfur batteries

Lithium-sulfur(Li-S)batteries have become a promising candidate for advanced energy storage system owing to low cost and high theoretical specific energy.In the last decade,in pursuit of Li-S batteries with enhanced safety and energy density,the investigation on the electrolytes has leaped form liquid organic electrolytes to solid polymer ones.However,such solid-state Li-S battery system is greatly limited by unfavorable ionic conductivity,poor interfacial contact and narrow electrochemical windows on account of the absence of any liquid components.To address these issues,gel polymer electrolytes(GPEs),the incorporation of liquid electrolytes into solid polymer matrixes,have been newly developed.Although the excellent ionic transport and low interfacial resistance provided by GPEs have prompted numerous researchers to make certain progress on high-performance Li-S coins,a comprehensive review on GPEs for Li-S batteries remains vacant.Herein,this review focuses on recent development and progress on GPEs in view of their physical and chemical properties for the applications in Li-S batteries.Studies on the components including solid hosts,liquid solutions and fillers of GPEs are systematically summarized with particular emphasis on the relationship between components and performance.Finally,current challenges and directional outlook for fabricating GPEs-based Li-S batteries with outstanding performance are outlined.

Observation of nonlinearity and heating-induced frequency shifts in cavity magnonics

When there is a certain amount of field inhomogeneity,the biased ferrimagnetic crystal can exhibit the higher-order magnetostatic(HMS)mode in addition to the uniform-precession Kittel mode.In cavity magnonics,we show the nonlinearity and heating-induced frequency shifts of the Kittel mode and HMS mode in a yttrium-iron-garnet(YIG)sphere.When the Kittel mode is driven to generate a certain number of excitations,the temperature of the whole YIG sample rises and the HMS mode can display an induced frequency shift,and vice versa.This cross effect provides a new method to study the magnetization dynamics and paves a way for novel cavity magnonic devices by including the heating effect as an operational degree of freedom.

Selecting flagship species to solve a biodiversity conservation conundrum

The difficulty of effectively monitoring and managing the environment to conserve biodiversity is as yet an unsolved conundrum.A project of the Chinese Academy of Sciences has concluded that progress can be made through the use of flagship species selected using criteria drawn from conservation biology,ecosystem function,socio-economics,and cultural importance.Inclusion of the latter three criteria will help attract and maintain the commitment of the public to play full parts in carrying out any conservation measures needed.A system is proposed for scoring species to select those that are most suitable as flagships.This method can be used regardless of the size of the area chosen for attention,whether it is a region,a country,or a particular protected area.

基于共轭共聚物网络的动态褶皱的多重调控

环境刺激响应的动态微/纳米图案可调节表面特性,为智能表面的按需制备提供了有效的解决方案.我们合成了一种光响应共轭聚合物(P(AEG-AAzo-AAN)),基于简单的策略构建了光驱动的双层动态褶皱图案系统.聚合物所含蒽侧基的光二聚和偶氮苯侧基的光异构化可以分别调节交联密度和应力松弛,从而决定褶皱的产生/擦除,实现多级次褶皱的按需制备.硫酸掺杂后,褶皱图案能够对湿度做出响应,薄膜变为半导体.这种多重响应动态褶皱可能在智能显示器和防伪标签中获得潜在的应用.

Intelligent design and construction of novel APN-based theranostic probe driven by advanced computational methods

Multifunctional molecules with both optical signal and pharmacological activity play an important role in drug development,disease diagnosis,and basic theoretical research.Aminopeptidase N(APN),as a representative tumor biomarker with anti-tumor potential,still lacks a high-precision theranostic probe specifically targeting it.In this study,a novel quaternity design strategy for APN theranostic probe was developed.This proposed strategy utilizes advanced machine learning and molecular dynamics simulations,and cleverly employs the strategy of conformation-induced fluorescence recovery to achieve multi-objective optimization and integration of functional fragments.Through this strategy,a unique“Off-On”theranostic probe,ABTP-DPTB,was ingeniously constructed to light up APN through fluorescence restoration,relying on conformation-induced effects and solvent restriction.Differ from the common diagnostic probes,the intelligent design with non-substrated linkage makes ABTP-DPTB for long-term in-situ imaging.The fabricated probe was used for detecting and inhibiting APN in various environments,with a better in vitro inhibitory than golden-standard drug bestatin.

Vasculopathy in dermatomyositis

To the Editor:Dermatomyositis(DM)is a rare autoimmune disease characterized by specific cutaneous manifestations and proximal muscle weakness,in which abnormalities of nailfold capillary(NFC)and serum levels of vascular biomarkers are common.Dynamic changes in vascular lesions play an important role in the occurrence and development of DM and reflect the disease activity and treatment efficacy.Due to the diversity of clinical manifestations in DM patients,vascular involvement is often under-evaluated,causing the treatment of refractory vascular damage challenging.This review aims to explore the mechanisms,clinical manifestations,and treatment options of vasculopathy in DM to achieve early recognition and improve prognosis.

LDL-C rebound after long-term evolocumab treatment and intravascular imaging evidence in a familial hypercholesterolemia patient with early-onset myocardial infarction

Patients with familial hypercholesterolemia(FH)have elevated low-density lipoprotein cholesterol(LDL-C)levels and are at high risk of premature cardiovascular disease.1 Heterozygous FH(HeFH)is one of the commonest genetic disorders,and is more frequent among those with ischemic heart disease(IHD),atherosclerotic cardiovascular disease(ASCVD)and premature IHD.

平均夜间基线阻抗对食管外症状胃食管反流病的临床诊断价值

目的探讨食管平均夜间基线阻抗(MNBI)对表现为食管外症状的胃食管反流病(GERD)的临床诊断价值。方法回顾性分析2018年1月至2019年12月期间以烧心、反流、咳嗽或声音嘶哑等为主要症状就诊于首都医科大学附属北京朝阳医院,并行24 h多通路腔内pH-阻抗监测的210例患者。按照诊断及分组标准将纳入患者分为四组,GERD食管外症状组39例、GERD典型症状组64例、GERD混合症状组52例及对照组55例。分析并比较各组间食管远端及近端平均夜间基线阻抗及其它反流参数。结果GERD食管外症状组的近端食管MNBI值、食管下段平均pH值低于典型症状组(P<0.05)。相关性分析显示近端及远端食管MNBI值与DeMeester积分、酸暴露时间和酸反流事件次数呈显著负相关(P<0.05)。食管外症状的GERD患者,近端食管MNBI值的诊断曲线下面积显著大于远端食管MNBI值的诊断曲线下面积(P<0.05),最佳诊断临界值为2484.38Ω,诊断敏感性及准确性分别达92.3%和84%,高于远端食管MNBI值的诊断敏感性及准确性。结论近端及远端食管MNBI值均与食管酸暴露相关。近端食管MNBI值可提高多通路pH-阻抗监测对食管外症状的GERD患者的检出率,具有重要的临床诊断价值。

Rational Design of Organelle-Targeted Fluorescent Probes:Insights from Artificial Intelligence

Monitoring the physiological changes of organelles is essential for understanding the local biological information of cells and for improving the diagnosis and therapy of diseases.Currently,fluorescent probes are considered as the most powerful tools for imaging and have been widely applied in biomedical fields.However,the expected targeting effects of these probes are often inconsistent with the real experiments.The design of fluorescent probes mainly depends on the empirical knowledge of researchers,which was inhibited by limited chemical space and low efficiency.Herein,we proposed a novel multilevel framework for the prediction of organelle-targeted fluorescent probes by employing advanced artificial intelligence algorithms.In this way,not only the targeting mechanism could be interpreted beyond intuitions but also a quick evaluation method could be established for the rational design.Furthermore,the targeting and imaging powers of the optimized and synthesized probes based on this methodology were verified by quantitative calculation and experiments.

Machine learning molecular dynamics simulations of liquid methanol

As the simplest hydrogen-bonded alcohol,liquid methanol has attracted intensive experimental and theoretical interest.However,theoretical investigations on this system have primarily relied on empirical intermolecular force fields or ab initio molecular dynamics with semilocal density functionals.Inspired by recent studies on bulk water using increasingly accurate machine learning force fields,we report a new machine learning force field for liquid methanol with a hybrid functional revPBE0 plus dispersion correction.Molecular dynamics simulations on this machine learning force field are orders of magnitude faster than ab initio molecular dynamics simulations,yielding the radial distribution functions,selfdiffusion coefficients,and hydrogen bond network properties with very small statistical errors.The resulting structural and dynamical properties are compared well with the experimental data,demonstrating the superior accuracy of this machine learning force field.This work represents a successful step toward a first-principles description of this benchmark system and showcases the general applicability of the machine learning force field in studying liquid systems.

Cardioprotective mechanism of SGLT2 inhibitor against myocardial infarction is through reduction of autosis

Sodium-glucose cotransporter 2(SGLT2)inhibitors reduce cardiovascular mortality in patients with diabetes mellitus but the protective mechanism remains elusive.Here we demonstrated that the SGLT2 inhibitor,Empagliflozin(EMPA),suppresses cardiomyocytes autosis(autophagic cell death)to confer cardioprotective effects.Using myocardial infarction(Ml)mouse models with and without diabetes mellitus,EMPA treatment significantly reduced infarct size,and myocardial fibrosis,thereby leading to improved cardiac function and survival.In the context of ischemia and nutritional glucose deprivation where autosis is already highly stimulated,EMPA directly inhibits the activity of the Na^(+)/H^(+)exchanger 1(NHE1)in the cardiomyocytes to regulate excessive autophagy.Knockdown of NHE1 significantly rescued glucose deprivation-induced autosis.In contrast,overexpression of NHE1 aggravated the cardiomyocytes death in response to starvation,which was effectively rescued by EMPA treatment.Furthermore,in vitro and in vivo analysis of NHE1 and Beclin 1 knockout mice validated that EMPA s cardioprotective effects are at least in part through downregulation of autophagic flux.These findings provide new insights for drug development,specifically targeting NHE1 and autosis for ventricular remodeling and heart failure after Ml in both diabetic and non-diabetic patients.

In vivo degradation and endothelialization of an iron bioresorbable scaffold

Detection of in vivo biodegradation is critical for development of next-generation medical devices such as bioresorbable stents or scaffolds(BRSs).In particular,it is urgent to establish a nondestructive approach to examine in vivo degradation of a new-generation coronary stent for interventional treatment based on mammal experiments;otherwise it is not available to semi-quantitatively monitor biodegradation in any clinical trial.Herein,we put forward a semi-quantitative approach to measure degradation of a sirolimus-eluting iron bioresorbable scaffold(IBS)based on optical coherence tomography(OCT)images;this approach was confirmed to be consistent with the present weight-loss measurements,which is,however,a destructive approach.The IBS was fabricated by a metal-polymer composite technique with a polylactide coating on an iron stent.The efficacy as a coronary stent of this new bioresorbable scaffold was compared with that of a permanent metal stent with the name of trade mark Xience,which has been widely used in clinic.The endothelial coverage on IBS was found to be greater than on Xience after implantation in a rabbit model;and our well-designed ultrathin stent exhibited less individual variation.We further examined degradation of the IBSs in both minipig coronary artery and rabbit abdominal aorta models.The present result indicated much faster iron degradation of IBS in the rabbit model than in the porcine model.The semi-quantitative approach to detect biodegradation of IBS and the finding of the species difference might be stimulating for fundamental investigation of biodegradable implants and clinical translation of the next-generation coronary stents.

Colonization of endophyte Acremonium sp. D212 in Panax notoginseng and rice mediated by auxin and jasmonic acid

Endophytic fungi can be beneficial to plant growth. However, the molecular mechanisms under-lying colonization of Acremonium spp. remain unclear. In this study, a novel endophytic Acremonium strain was isolated from the buds of Panax notoginseng and named Acremonium sp. D212. The Acremonium sp. D212 could colonize the roots of P. notoginseng, enhance the resistance of P. notoginseng to root rot disease, and promote root growth and saponin bio-synthesis in P. notoginseng. Acremonium sp. D212 could secrete indole-3-acetic acid (IAA) and jasmonic acid (JA), and inoculation with the fungus increased the endogenous levels of IAA and JA in P. noto-ginseng. Colonization of the Acremonium sp. D212 in the roots of the rice line Nipponbare was dependent on the concentration of methyl jasmonate (MeJA) (2–15μmol/L) and 1-naphthalenacetic acid (NAA) (10–20μmol/L). Moreover, the roots of the JA signaling-defective coi1-18 mutant were colonized by Acremonium sp. D212 to a lesser degree than those of the wild-type Nipponbare and miR393b-overexpressing lines, and the colonization was res-cued by MeJA but not by NAA. It suggests that the cross-talk between JA signaling and the auxin biosynthetic pathway plays a crucial role in the colonization of Acremonium sp. D212 in host plants.

Arabidopsis mitochondrial single-stranded DNA-binding proteins SSB1 and SSB2 are essential regulators of mtDNA replication and homologous recombination

Faithful DNA replication is one of the most essential processes in almost all living organisms.However,the proteins responsible for organellar DNA replication are still largely unknown in plants.Here,we show that the two mitochondriontargeted single-stranded DNA-binding(SSB)proteins SSB1 and SSB2 directly interact with each other and act as key factors for mitochondrial DNA(mt DNA)maintenance,as their single or double loss-of-function mutants exhibit severe germination delay and growth retardation.The mt DNA levels in mutants lacking SSB1 and/or SSB2 function were two-to four-fold higher than in the wild-type(WT),revealing a negative role for SSB1/2 in regulating mt DNA replication.Genetic analysis indicated that SSB1 functions upstream of mitochondrial DNA POLYMERASE IA(POLIA)or POLIB in mt DNA replication,as mutation in either gene restored the high mt DNA copy number of the ssb1-1 mutant back to WT levels.In addition,SSB1 and SSB2 also participate in mitochondrial genome maintenance by influencing mt DNA homologous recombination(HR).Additional genetic analysis suggested that SSB1 functions upstream of ORGANELLAR SINGLE-STRANDED DNABINDING PROTEIN1(OSB1)during mt DNA replication,while SSB1 may act downstream of OSB1and MUTS HOMOLOG1 for mt DNA HR.Overall,our results yield new insights into the roles of the plant mitochondrion-targeted SSB proteins and OSB1 in maintaining mt DNA stability via affecting DNA replication and DNA HR.