Alzheimer's disease,the primary cause of dementia,is characterized by neuropathologies,such as amyloid plaques,synaptic and neuronal degeneration,and neurofibrillary tangles.Although amyloid plaques are the primar...Alzheimer's disease,the primary cause of dementia,is characterized by neuropathologies,such as amyloid plaques,synaptic and neuronal degeneration,and neurofibrillary tangles.Although amyloid plaques are the primary characteristic of Alzheimer's disease in the central nervous system and peripheral organs,targeting amyloid-beta clearance in the central nervous system has shown limited clinical efficacy in Alzheimer's disease treatment.Metabolic abnormalities are commonly observed in patients with Alzheimer's disease.The liver is the primary peripheral organ involved in amyloid-beta metabolism,playing a crucial role in the pathophysiology of Alzheimer's disease.Notably,impaired cholesterol metabolism in the liver may exacerbate the development of Alzheimer's disease.In this review,we explore the underlying causes of Alzheimer's disease and elucidate the role of the liver in amyloid-beta clearance and cholesterol metabolism.Furthermore,we propose that restoring normal cholesterol metabolism in the liver could represent a promising therapeutic strategy for addressing Alzheimer's disease.展开更多
The excessive buildup of neurotoxicα-synuclein plays a pivotal role in the pathogenesis of Parkinson's disease,highlighting the urgent need for innovative therapeutic strategies to promoteα-synuclein clearance,p...The excessive buildup of neurotoxicα-synuclein plays a pivotal role in the pathogenesis of Parkinson's disease,highlighting the urgent need for innovative therapeutic strategies to promoteα-synuclein clearance,particularly given the current lack of disease-modifying treatments.The glymphatic system,a recently identified perivascular fluid transport network,is crucial for clearing neurotoxic proteins.This review aims to synthesize current knowledge on the role of the glymphatic system inα-synuclein clearance and its implications for the pathology of Parkinson's disease while emphasizing potential therapeutic strategies and areas for future research.The review begins with an overview of the glymphatic system and details its anatomical structure and physiological functions that facilitate cerebrospinal fluid circulation and waste clearance.It summarizes emerging evidence from neuroimaging and experimental studies that highlight the close correlation between the glymphatic system and clinical symptom severity in patients with Parkinson's disease,as well as the effect of glymphatic dysfunction onα-synuclein accumulation in Parkinson's disease models.Subsequently,the review summarizes the mechanisms of glymphatic system impairment in Parkinson's disease,including sleep disturbances,aquaporin-4 impairment,and mitochondrial dysfunction,all of which diminish glymphatic system efficiency.This creates a vicious cycle that exacerbatesα-synuclein accumulation and worsens Parkinson's disease.The therapeutic perspectives section outlines strategies for enhancing glymphatic activity,such as improving sleep quality and pharmacologically targeting aquaporin-4 or its subcellular localization.Promising interventions include deep brain stimulation,melatonin supplementation,γ-aminobutyric acid modulation,and non-invasive methods(such as exercise and bright-light therapy),multisensoryγstimulation,and ultrasound therapy.Moreover,identifying neuroimaging biomarkers to assess glymphatic flow as an indicator ofα-synuclein burden could refine Parkinson's disease diagnosis and track disease progression.In conclusion,the review highlights the critical role of the glymphatic system inα-synuclein clearance and its potential as a therapeutic target in Parkinson's disease.It advocates for further research to elucidate the specific mechanisms by which the glymphatic system clears misfoldedα-synuclein and the development of imaging biomarkers to monitor glymphatic activity in patients with Parkinson's disease.Findings from this review suggest that enhancing glymphatic clearance is a promising strategy for reducingα-synuclein deposits and mitigating the progression of Parkinson's disease.展开更多
The existence of the aeroengine casing,limited monitoring points,and multi-fault characteristics make obtaining the rotor’s vibration transmission characteristics challenging,resulting in difficulties accurately iden...The existence of the aeroengine casing,limited monitoring points,and multi-fault characteristics make obtaining the rotor’s vibration transmission characteristics challenging,resulting in difficulties accurately identifying the rotor unbalance.This paper utilizes a high-frequency composite sensor to monitor the engine’s blade tip clearance(BTC)and extracts unbalanced information from BTC signals for rotor dynamic balancing,while avoiding the need for the once per revolution(OPR)sensor.First,the vibration characteristics of the rotor-blade system under multi-fault conditions are investigated.Then,based on BTC measurement,a none OPR method and an unbalance identification method are proposed,in which the radial vibration of the blade tip in the BTC signals at different speeds is extracted and operated in the time domain to obtain the rotor unbalanced vibration,the signal is reconstructed,and cross-correlation analysis is used to accurately identify the magnitude and phase of the unbalanced signal.Finally,a rotor test bench is utilized for experimental verification.The results reveal that the dynamic balancing method based on the BTC signal can more precisely identify the rotor unbalance than the traditional rotor dynamic balancing method.The application of this technique will effectively improve engine health management and fault prediction.展开更多
Currently,it is still a challenge to develop an organic photosensitizer(PS)with outstanding near-infrared absorption,low O2dependence,precise tumor targeting and rapid clearance through the kidney to improve the overa...Currently,it is still a challenge to develop an organic photosensitizer(PS)with outstanding near-infrared absorption,low O2dependence,precise tumor targeting and rapid clearance through the kidney to improve the overall outcome of phototherapy.In this study,we have designed an organic PS(Nc PB)with an excellent near-infrared light absorption through a refined molecular strategy.Meanwhile,Nc PB was assembled into nanoparticles with different sizes(Nano Nc PB-1 and Nano Nc PB-0)by a supramolecular modulation strategy.As the results,the nanoparticle with an ultra-small size(Nano Nc PB-1)generated a large number of superoxide anion(O_(2)^(·-))in a low-O_(2)-dependent manner and release plenty of heat.Furthermore,the results of in vivo experiments demonstrated that Nano Nc PB-1 actively accumulated in tumor tissues and showed a 92%tumor inhibition after photodynamic and photothermal combination therapy.More importantly,Nano Nc PB-1 could be rapidly cleared from the body of mice via the renal pathway,which alleviates potential side effects of prolonged retention of PS in the circulation.展开更多
Combining practical engineering projects, this article analyzes the design strategies for the reconstruction and expansion of insufficient clearance sections in highway interchanges. This includes an overview of the p...Combining practical engineering projects, this article analyzes the design strategies for the reconstruction and expansion of insufficient clearance sections in highway interchanges. This includes an overview of the project, a comparison of design options for insufficient clearance in interchanges, and the main design strategies for reconstruction and expansion. It is hoped that this analysis can provide a reference for the design of such road reconstruction and expansion projects.展开更多
Metamorphic mechanism has the advantages of variable topology and variable degrees of freedom, which can realize the requirements of multi-conditions and multi-tasks, and has a good application prospect. The configura...Metamorphic mechanism has the advantages of variable topology and variable degrees of freedom, which can realize the requirements of multi-conditions and multi-tasks, and has a good application prospect. The configuration transformation is prominent feature of the metamorphic mechanism. The number of constraints or properties of the kinematic pairs provided by the metamorphic kinematic pairs will change under certain conditions, its dynamic performance is much more complex than that of traditional kinematic pairs with immutable constraints. However, the clearance model about traditional kinematic pairs with immutable constraints established by long-term research is difficult to be directly applied to the metachromatic kinematic pairs. Referring to the experience of the traditional kinematic pairs with immutable constraints, the continuous contact model of Metamorphic Groove pin pair with clearance is established. According to the traditional continuous contact model of the kinematic pairs with immutable constraints, the forces between the elements of kinematic pair of the mechanism with clearance and the ideal mechanism without clearance are regarded as the same, and the inertia force and inertia moment of the components are also calculated according to the acceleration of the ideal mechanism. The clearance is regarded as a massless virtual bar with length r. For the rotating pair part, the massless virtual bar length r is the difference between the radius of the shaft and the hole, and for the sliding pair part, the massless virtual bar length r is half of the difference between the height of the slider and the guide groove. According to the new mechanism without gap after adding the imaginary bar, kinetic energy and potential energy of the system are calculated for the two configurations of mechanism with metamorphic Groove pin pair with clearance. The kinetic energy and potential energy of the system are calculated according to the new mechanism without clearance after adding the massless virtual bar. The kinetic energy, potential energy and generalized force are substituted into the Lagrangian equation to obtain the motion equation of the metamorphic mechanism, which lays the foundation for the dynamic performance study of the mechanism with metamorphic groove pin pair with clearance.展开更多
As the performance of the box-type multiple launch rocket system(BMLRS)improves,its mechanical structures,particularly the plane clearance design between the slider on the rocket and the guide inside the launch canist...As the performance of the box-type multiple launch rocket system(BMLRS)improves,its mechanical structures,particularly the plane clearance design between the slider on the rocket and the guide inside the launch canister,have grown increasingly complex.However,deficiencies still exist in the current launch modeling theory for BMLRS.In this study,a multi-rigid-flexible-body launch dynamics model coupling the launch platform and rocket was established using the multibody system transfer matrix method and the Newton-Euler formulation.Furthermore,considering the bending of the launch canister,a detection algorithm for slider-guide plane clearance contact was proposed.To quantify the contact force and friction effect between the slider and guide,the contact force model and modified Coulomb model were introduced.Both the modal and launch tests were conducted.Additionally,the modal convergence was verified.By comparing the modal experiments and simulation results,the maximum relative error of the eigenfrequency is 3.29%.thereby verifying the accuracy of the developed BMLRS dynamics model.Furthermore,the launch test validated the proposed plane clearance contact model.Moreover,the study investigated the influence of various model parameters on the dynamic characteristics of BMLRS,including launch canister bending stiffness,slider and guide material,slider-guide clearance,slider length and layout.This analysis of influencing factors provides a foundation for future optimization in BMLRS design.展开更多
Advancements in murine modeling systems for ulcerative colitis have diversified our understanding of the pathophysiological factors involved in disease onset and progression.This has fueled the identification of molec...Advancements in murine modeling systems for ulcerative colitis have diversified our understanding of the pathophysiological factors involved in disease onset and progression.This has fueled the identification of molecular targets,resulting in a rapidly expanding therapeutic armamentarium.Subsequently,management strategies have evolved from symptomatic resolution to well-defined objective endpoints,including clinical remission,endoscopic remission and mucosal healing.While the incorporation of these assessment modalities has permitted targeted intervention in the context of a natural disease history and the prevention of complications,studies have consistently depicted discrepancies associated with ascertaining disease status through clinical and endoscopic measures.Current recommendations lack consideration of histological healing.The simultaneous achievement of clinical,endoscopic,and histologic remission has not been fully investigated.This has laid the groundwork for a novel therapeutic outcome termed disease clearance(DC).This article summarizes the concept of DC and its current evidence.展开更多
Objective:Augmented renal clearance(ARC),in contrast to renal dysfunction,refers to enhanced renal elimination of circulating solutes compared to the expected baseline.Although patients may present with normal serum c...Objective:Augmented renal clearance(ARC),in contrast to renal dysfunction,refers to enhanced renal elimination of circulating solutes compared to the expected baseline.Although patients may present with normal serum creatinine(Scr)levels,the incidence of ARC is high in intensive care unit(ICU)settings.ARC is associated with subtherapeutic exposure and treatment failure of renally cleared antibiotics.However,limited research exists on the incidence and risk factors of ARC in the ICU,and even fewer data are available specifically for neurological ICU(NICU).This study aims to determine the incidence and risk factors of ARC in neurocritically ill patients.Methods:We retrospectively analyzed all available Scr data of neurocritical care patients admitted to the NICU of the Second Xiangya Hospital of Central South University between December 2020 and January 2023.Creatinine clearance(CrCl)was calculated using the Cockcroft-Gault equation.ARC was defined as a CrCl≥130 mL/(min·1.73 m^(2))sustained for more than 50%of the duration of the NICU stay.A total of 208 neurocritically ill patients were assigned into an ARC group(n=52)and a non-ARC(N-ARC)group(n=156).Clinical characteristics were compared between the 2 groups.Variables with P<0.05 in univariate analysis were included in binary Logistic regression to identify independent risk factors for ARC.Results:The incidence of ARC among neurocritically ill patients was 25.00%.Of the 74 patients with normal CrCl,20(27.03%)gradually developed ARC during hospitalization.Compared with the N-ARC group,the patients of the ARC group were younger(P<0.001),with a higher proportion of females(P=0.048)and a lower admission mean arterial pressure(MAP)(P=0.034).Moreover,patients of the ARC group were commonly complicated with severe bacterial infections compared with the patients of the N-ARC group(P<0.001).In binary Logistic regression analysis,younger age(OR=0.903,95%CI 0.872 to 0.935)and severe bacterial infections(OR=6.270,95%CI 2.568 to 15.310)were significant predictors of ARC.Conclusion:ARC is relatively common in the NICU.A considerable number of patients with initially normal renal function developed ARC during hospitalization.Younger age and concurrent severe bacterial infection are important risk factors of ARC in neurocritically ill patients.展开更多
This article describes the effects of some factors on the tip clearance flow in axial linear turbine cascades. The measurements of the total pressure loss coefficient are made at the cascade outlets by using a five-ho...This article describes the effects of some factors on the tip clearance flow in axial linear turbine cascades. The measurements of the total pressure loss coefficient are made at the cascade outlets by using a five-hole probe at exit Mach numbers of 0.10, 0.14 and 0.19. At each exit Mach number, experiments are performed at the tip clearance heights of 1.0%, 1.5%, 2.0%, 2.5% and 3.0% of the blade height. The effects of the non-uniform tip clearance height of each blade in the pitchwise direction are also studied. The results show that at a given tip clearance height, generally, total pressure loss rises with exit Mach numbers proportionally. At a fixed exit Mach number, the total pressure loss augments nearly proportionally as the tip clearance height increases. The increased tip clearance heights in the tip regions of two adjacent blades are to be blame for the larger clearance loss of the center blade. Compared to the effects of the tip clearance height, the effects of the exit Mach number and the pitchwise variation of the tip clearance height on the cascade total pressure loss are so less significant to be omitted.展开更多
Joint clearances in antenna pointing mechanisms lead to uncertainty in function deviation. Current studies mainly focus on radial clearance of revolute joints, while axial clearance has rarely been taken into consider...Joint clearances in antenna pointing mechanisms lead to uncertainty in function deviation. Current studies mainly focus on radial clearance of revolute joints, while axial clearance has rarely been taken into consideration. In fact, own?ing to errors from machining and assembly, thermal deformation and so forth, practically, axial clearance is inevitable in the joint. In this study, an error equivalent model(EEM) of revolute joints is proposed with considering both radial and axial clearances. Compared to the planar model of revolute joints only considering radial clearance, the journal motion inside the bearing is more abundant and matches the reality better in the EEM. The model is also extended for analyzing the error distribution of a spatial dual?axis("X–Y" type) antenna pointing mechanism of Spot?beam antennas which especially demand a high pointing accuracy. Three case studies are performed which illustrates the internal relation between radial clearance and axial clearance. It is found that when the axial clearance is big enough, the physical journal can freely realize both translational motion and rotational motion. While if the axial clearance is limited, the motion of the physical journal will be restricted. Analysis results indicate that the consideration of both radial and axial clearances in the revolute joint describes the journal motion inside the bearing more precise. To further validate the proposed model, a model of the EEM is designed and fabricated. Some suggestions on the design of revolute joints are also provided.展开更多
Lateral clearance on the inside of horizontal curves is required by all geometric design guidelines in order to provide at least stopping sight distance. There already exist graphical models, analytical models, and de...Lateral clearance on the inside of horizontal curves is required by all geometric design guidelines in order to provide at least stopping sight distance. There already exist graphical models, analytical models, and design charts for determining minimum clearance offsets to meet the requirement. Some of these models determine the offsets based on constant design sight distance values on the assumption that drivers negotiate horizontal curves at constant speed. Therefore, those models are suitable for sites where there is no difference in speeds between tangent and curved sections. Past studies have reported that there are sites where drivers decelerate on entering horizontal curves and accelerate on departing from the curves. At those sites stopping sight distance for a given driver varies with driver location due to variable speed. This paper presents an analytical model and a chart for determining minimum offsets needed to provide desired sight distances at horizontal curves with variable operating speeds. At those sites the offsets yield roadside clearance boundaries that have transition arcs with performances that are similar to those of elliptical arcs. Therefore, practitioners may choose to use elliptical equations or equations and the chart developed herein. Results of this study will be of value to practitioners in the area of roadside design.展开更多
Active control of turbine blade tip clearance continues to be a concern in design and control of gas turbines. Ever increasing demands for improved efficiency and higher operating temperatures require more stringent t...Active control of turbine blade tip clearance continues to be a concern in design and control of gas turbines. Ever increasing demands for improved efficiency and higher operating temperatures require more stringent tolerances on turbine tip clearance. In this paper, a turbine tip clearance control apparatus and a model of turbine tip clearance are proposed; an implicit active generalized predictive control （GPC）, with auto-regressive （AR） error modification and fuzzy adjustment on control horizon, is presented, as well as a quantitative analysis method of robust per- turbation radius of the system. The active clearance control （ACC） of aero-engine turbine tip clear- ance is evaluated in a lapse-rate take-off transient, along with the comparative and quantitative analysis of the stability and robustness of the active tip clearance control system. The results show that the resultant active tip clearance control system with the improved GPC has favorable steadystate and dynamic performance and benefits of increased efficiency, reduced specific fuel consump- tion, and additional service life.展开更多
Experiment and numerical simulation technique are used to investigate the tip leakage flow in an axial fan with tip clearance at the design condition. The flow field in the tip region of fan is measured using a PDA (P...Experiment and numerical simulation technique are used to investigate the tip leakage flow in an axial fan with tip clearance at the design condition. The flow field in the tip region of fan is measured using a PDA (Particle Dynamics Analysis) system. The flow is surveyed across the whole passage at fifteen axial locations (from the 100% axial chord in front of the leading edge to the 100% axial chord behind the trailing edge), mainly focusing on the outer 90% blade span. Both experiment measurement and numerical simulation indicates the leakage flow originated from the tip clearance along the chord rolls up into three dimensional spiral structure to form leakage flow vortex. The interaction of leakage flow and main flow will produce the low velocity zone, and block the flow. The leakage flow almost occupies the most part of flow passage behind the trailing edge.展开更多
A centrifugal fan with the high speed and compact dimensions is studied numerically and experimentally. The centrifugal fan consists of a shrouded impeller rotating at 34 000 r/min with a small tip clearance 0.7 mm to...A centrifugal fan with the high speed and compact dimensions is studied numerically and experimentally. The centrifugal fan consists of a shrouded impeller rotating at 34 000 r/min with a small tip clearance 0.7 mm to the fixed outer casing. Computational models with/without the tip clearance are built and the κ-ω shear stress transport （SST） turbulence model and the unstructured mesh are applied to the numerical simulation for unsteady solutions. The overall performance is measured on a standard experimental bench and the major flow feature of each component inside the centrifugal fan is numerically investigated. In the presence of the tip clearance due to the difference of static pressure between leading and trailing edges of the clearance, i. e. , leading and trailing edges of the impeller, a strong return flow exists inside the clearance passage and re-circulates the main stream inside the impeller passage, and produces the strong flow interaction, thus changing the flow field and influencing the overall performance.展开更多
Thin-walled tube numerical control （NC） bending is a tri-nonlinear physical process with multi-defect and multi-die constraints. The clearance on each contact interface is the major factor to indicate the contact co...Thin-walled tube numerical control （NC） bending is a tri-nonlinear physical process with multi-defect and multi-die constraints. The clearance on each contact interface is the major factor to indicate the contact conditions. A three-dimensional-finite element （3D-FE） model is established to consider the realistic dynamic boundary conditions of multiple dies under ABAQUS/Explicit platform. Combined with experiment, numerical study on bending behavior and bendability under different clearance between tube and various dies is conducted in terms of wrinkling, wall thinning and cross section deformation. The results show that （1）with smaller clearance of tube-wiper die and tube-mandrel, the wrinkling can be restrained while the wall thinning It and cross-section deformation Id increase; while excessive small clearance blocks tube materials to flow past tangent point and causes piles up, the onset of wrinkling enhances It and Id. （2）Both It and Id decrease with smaller clearance of tube-pressure die; the wrinkling possibility rises with larger clearance on this interface if the mandrel’s freedom along Y-axis is opened; smaller clearance of tube-bend die prevents wrinkling while increases It, and the clearance on this interface has little effect on Id. （3）A modified Yoshida buckling test （YBT） is used to address the wrinkling mechanisms under normal constraints in tube bending： the smaller clearance may restrain wrinkling efficiently; the smaller wall thickness, the less critical clearance needed; the critical clearance for tube bending 38 mm×1 mm×57 mm （tube outer diameter×wall thickness×centerline bending radius） equals about 20% of initial wall thickness.展开更多
BACKGROUND Nucleos(t)ide analog(NA)has shown limited effectiveness against hepatitis B surface antigen(HBsAg)clearance in chronic hepatitis B(CHB)patients.AIM To evaluate the efficacy and safety of add-on peginterfero...BACKGROUND Nucleos(t)ide analog(NA)has shown limited effectiveness against hepatitis B surface antigen(HBsAg)clearance in chronic hepatitis B(CHB)patients.AIM To evaluate the efficacy and safety of add-on peginterferonα-2a(peg-IFNα-2a)to an ongoing NA regimen in CHB patients.METHODS In this observational study,195 CHB patients with HBsAg≤1500 IU/m L,hepatitis B e antigen(HBeAg)-negative(including HBeAg-negative patients or HBeAg-positive patients who achieved HBeAg-negative after antiviral treatment with NA)and hepatitis B virus-deoxyribonucleic acid<1.0×10^2 IU/mL after over 1 year of NA therapy were enrolled between November 2015 and December2018 at the Second Affiliated Hospital of Xi'an Jiaotong University,China.Patients were given the choice between receiving either peg-IFNα-2a add-on therapy to an ongoing NA regimen(add-on group,n=91)or continuous NA monotherapy(monotherapy group,n=104)after being informed of the benefits and risks of the peg-IFNα-2a therapy.Total therapy duration of peg-IFNα-2a was 48 wk.All patients were followed-up to week 72(24 wk after discontinuation of peg-IFNα-2a).The primary endpoint was the proportion of patients with HBsAg clearance at week 72.RESULTS Demographic and baseline characteristics were comparable between the two groups.Intention-to-treatment analysis showed that the HBsAg clearance rate in the add-on group and monotherapy group was 37.4%(34/91)and 1.9%(2/104)at week 72,respectively.The HBsAg seroconversion rate in the add-on group was 29.7%(27/91)at week 72,and no patient in the monotherapy group achieved HBsAg seroconversion at week 72.The HBsAg clearance and seroconversion rates in the add-on group were significantly higher than in the monotherapy group at week 72(P<0.001).Younger patients,lower baseline HBsAg concentration,lower HBsAg concentrations at weeks 12 and 24,greater HBsAg decline from baseline to weeks 12 and 24 and the alanine aminotransferase≥2×upper limit of normal during the first 12 wk of therapy were strong predictors of HBsAg clearance in patients with peg-IFNα-2a add-on treatment.Regarding the safety of the treatment,4.4%(4/91)of patients in the add-on group discontinued peg-IFNα-2a due to adverse events.No severe adverse events were noted.CONCLUSION Peg-IFNα-2a as an add-on therapy augments HBsAg clearance in HBeAg-negative CHB patients with HBsAg≤1500 IU/m L after over 1 year of NA therapy.展开更多
Objective:To explore the easily applicable indicators of practical value to evaluate the prognosis of acute respiratory distress syndrome（ARDS）.Methods:Blood and biochemical tests and bloodgas analyses were performe...Objective:To explore the easily applicable indicators of practical value to evaluate the prognosis of acute respiratory distress syndrome（ARDS）.Methods:Blood and biochemical tests and bloodgas analyses were performed upon entry into the ICUs,12 h,24 h,48 h and 72 h after that in 72 ARDS patients（who were admitted to the ICUs of our hospital from January 2000 to December 2009）.Then APACHEⅡscores were achieved by combining relevant physiological parameters and laboratory results.Results:There was a statistical difference between the death group and survival group at different time points upon entering the ICUs in terms of APACHEⅡscore, alveolar-arterial oxygen difference and arterial blood lactate clearance rate.PaO<sub>2</sub>/FiO<sub>2</sub> values were recorded to be statistically different between the death group and survival group 24 h,48 h and 72 h,respectively after entry into the ICUs.In addition,registered linear regression existed between APACHEⅡscore,alveolar-arterial oxygen difference or PaO<sub>2</sub>/FiO<sub>2</sub> value and time. APACHEⅡscore 24 h and 72 h after entering ICUs predicted mortality with an area under the ROC curve（AUC） standing respectively at 0.919 and 0.9SS.Arterial blood lactate clearance rate 12 h, 24 h,48 h and 72 h after entering ICUs predicted mortality with an area under the ROC curve （AUC） at 0.918,0.918,0.909 and 0.991,respectively.Conclusions:APACHEⅡscore applied in combination with arterial blood lactate clearance rate is of clinical significance in assessing the prognosis of ARDS patients.展开更多
The inner and outer oil film dynamic characteristic coefficients of floating ring bearings（FRBs） change due to the manufacturing tolerance of the floating ring, journal and intermediate, which leads to high-speed tu...The inner and outer oil film dynamic characteristic coefficients of floating ring bearings（FRBs） change due to the manufacturing tolerance of the floating ring, journal and intermediate, which leads to high-speed turbocharger＇s vibration too large and even causes nonlinear vibration accident. However, the investigation of floating ring bearing manufacturing tolerance clearance on the rotordynamic characteristics is less at present. In order to study the influence law of inner and outer clearance on turbocharger vibration, the rotor dynamic motion equations of turbocharger supported in FRBs are derived by analyzing the size relations between floating ring, journal and intermediate for the inner and outer oil film clearances, the time transient response analysis for combination of FRBs clearance are developed. A realistic turbocharger is taken as a research object, the FE model of the turbocharger with FRBs is modeled. Under the conditions of four kinds of limit state bearing clearances for inner and outer oil film, the nonlinear transient analyses are performed based on the established FE dynamic models of the nonlinear rotor-FRBs system applied incentive combinations of gravity and unbalance force, respectively. From the waterfall, the simulation results show that the speed for the appearance of fractional frequency is not identical and the amplitude magnitude is different under the four kinds of bearing manufacturing tolerance limit clearances, and fractional frequency does not appear in the turbocharger and the amplitude is minimum under the ODMin/IDMax bearing manufacturing tolerance clearances. The turbocharger vibration is reduced by controlling the manufacturing tolerance clearance combinations of FRBs, which is helpful for the dynamic design and production-manufacturing of high-speed turbocharger.展开更多
BACKGROUND: Acute liver failure(ALF) is an acute severe deterioration of liver function with high mortality. Early and accurate prognostic assessment of patients with ALF is critically important. Although the model fo...BACKGROUND: Acute liver failure(ALF) is an acute severe deterioration of liver function with high mortality. Early and accurate prognostic assessment of patients with ALF is critically important. Although the model for end-stage liver disease(MELD) scores and King’s College Hospital(KCH) criteria are well-accepted as predictive tools, their accuracy is unsatisfactory.The indocyanine green(ICG) clearance test(ICGR15, ICG retention rate at the 15 minutes) is a sensitive indicator of liver function. In this study, we investigated the efficacy of the ICGR15 for the short-term prognosis in patients with ALF. We compared the predictive value of ICGR15 with the MELD scores and KCH criteria.METHODS: Sixty-nine patients who had been diagnosed with ALF were recruited retrospectively. ICGR15 had been performed by ICG pulse spectrophotometry and relevant clinical and laboratory indices were analyzed within 24 hours of diagnosis.In addition, the MELD scores and KCH criteria were calculated.RESULTS: The three-month mortality of all patients was 47.83%.Age, serum total bilirubin and creatinine concentrations,international normalized ratio for prothrombin time, ICGR15,MELD scores and KCH criteria differed significantly between surviving and deceased patients. A positive correlation was observed between ICGR15 and MELD scores(r=0.328, P=0.006).The ICGR15-MELD model, Logit(P)=0.096×ICGR15+0.174 ×MELD score–9.346, was constructed by logistic regression analysis. The area under the receiver operating characteristic curve was 0.855. When set the cut-off point to-0.4684, the sensitivity was 87.90% and specificity, 72.20%. The area under the receiver operating characteristic curve of the ICGR15-MELD model(0.855) was significantly higher than that of the ICGR15(0.793), MELD scores(0.776) and KCH criteria(0.659).Based on this cut-off value, the patients were divided into two groups. The mortality was 74.36% in the first group(ICGR15-MELD≥-0.4686) and 13.33% in the second group(ICGR15-MELD<-0.4686), with a significant difference between the two groups(χ2=25.307, P=0.000).CONCLUSION: The ICGR15-MELD model is superior to the ICGR15, MELD scores, and KCH criteria in predicting the shortterm prognosis of patients with ALF.展开更多
基金financially supported by the Science and Technology Innovation Program of Hunan Province,No.2022RC1220(to WP)China Postdoctoral Science Foundation,No.2022M711733(to ZZ)+2 种基金the National Natural Science Foundation of China,No.82160920(to ZZ)Hebei Postdoctoral Scientific Research Project,No.B2022003040(to ZZ)Hunan Flagship Department of Integrated Traditional Chinese and Western Medicine(to WP)。
文摘Alzheimer's disease,the primary cause of dementia,is characterized by neuropathologies,such as amyloid plaques,synaptic and neuronal degeneration,and neurofibrillary tangles.Although amyloid plaques are the primary characteristic of Alzheimer's disease in the central nervous system and peripheral organs,targeting amyloid-beta clearance in the central nervous system has shown limited clinical efficacy in Alzheimer's disease treatment.Metabolic abnormalities are commonly observed in patients with Alzheimer's disease.The liver is the primary peripheral organ involved in amyloid-beta metabolism,playing a crucial role in the pathophysiology of Alzheimer's disease.Notably,impaired cholesterol metabolism in the liver may exacerbate the development of Alzheimer's disease.In this review,we explore the underlying causes of Alzheimer's disease and elucidate the role of the liver in amyloid-beta clearance and cholesterol metabolism.Furthermore,we propose that restoring normal cholesterol metabolism in the liver could represent a promising therapeutic strategy for addressing Alzheimer's disease.
基金supported by the National Natural Science Foundation of China,No.81971031(to ZL)the National Key Research and Development Program of China,No.2022YFE0210100(to JFC)+7 种基金the National Natural Science Foundation of China(Original Exploration Project),No.82151308(to JFC)the National Natural Science Foundation of China(Research Fund for International Senior Scientists),No.82150710558(to JFC)Science&Technology Initiative STI2030-Major Projects,No.2021ZD0203400(to JFC)Key Research and Development Program of Zhejiang Province,No.2023C03079(to JFC)Scientific Research Starting Foundation of Oujiang Laboratory(Zhejiang Laboratory for Regenerative Medicine,Vision and Brain Health),No.OJQDSP2022007(to JFC)Project of State Key Laboratory of Ophthalmology,Optometry and Visual Science,Wenzhou Medical University,No.J01-20190101(to JFC)Scientific Research Starting Foundation of Wenzhou Medical University,No.QTJ12003(to JFC)Department of Science and Technology of Zhejiang Province,No.2023ZY1011(to JFC)。
文摘The excessive buildup of neurotoxicα-synuclein plays a pivotal role in the pathogenesis of Parkinson's disease,highlighting the urgent need for innovative therapeutic strategies to promoteα-synuclein clearance,particularly given the current lack of disease-modifying treatments.The glymphatic system,a recently identified perivascular fluid transport network,is crucial for clearing neurotoxic proteins.This review aims to synthesize current knowledge on the role of the glymphatic system inα-synuclein clearance and its implications for the pathology of Parkinson's disease while emphasizing potential therapeutic strategies and areas for future research.The review begins with an overview of the glymphatic system and details its anatomical structure and physiological functions that facilitate cerebrospinal fluid circulation and waste clearance.It summarizes emerging evidence from neuroimaging and experimental studies that highlight the close correlation between the glymphatic system and clinical symptom severity in patients with Parkinson's disease,as well as the effect of glymphatic dysfunction onα-synuclein accumulation in Parkinson's disease models.Subsequently,the review summarizes the mechanisms of glymphatic system impairment in Parkinson's disease,including sleep disturbances,aquaporin-4 impairment,and mitochondrial dysfunction,all of which diminish glymphatic system efficiency.This creates a vicious cycle that exacerbatesα-synuclein accumulation and worsens Parkinson's disease.The therapeutic perspectives section outlines strategies for enhancing glymphatic activity,such as improving sleep quality and pharmacologically targeting aquaporin-4 or its subcellular localization.Promising interventions include deep brain stimulation,melatonin supplementation,γ-aminobutyric acid modulation,and non-invasive methods(such as exercise and bright-light therapy),multisensoryγstimulation,and ultrasound therapy.Moreover,identifying neuroimaging biomarkers to assess glymphatic flow as an indicator ofα-synuclein burden could refine Parkinson's disease diagnosis and track disease progression.In conclusion,the review highlights the critical role of the glymphatic system inα-synuclein clearance and its potential as a therapeutic target in Parkinson's disease.It advocates for further research to elucidate the specific mechanisms by which the glymphatic system clears misfoldedα-synuclein and the development of imaging biomarkers to monitor glymphatic activity in patients with Parkinson's disease.Findings from this review suggest that enhancing glymphatic clearance is a promising strategy for reducingα-synuclein deposits and mitigating the progression of Parkinson's disease.
基金supported by the Key Program of National Natural Science Foundation of China(No.92160203)National Natural Science Foundation of China(No.92360306).
文摘The existence of the aeroengine casing,limited monitoring points,and multi-fault characteristics make obtaining the rotor’s vibration transmission characteristics challenging,resulting in difficulties accurately identifying the rotor unbalance.This paper utilizes a high-frequency composite sensor to monitor the engine’s blade tip clearance(BTC)and extracts unbalanced information from BTC signals for rotor dynamic balancing,while avoiding the need for the once per revolution(OPR)sensor.First,the vibration characteristics of the rotor-blade system under multi-fault conditions are investigated.Then,based on BTC measurement,a none OPR method and an unbalance identification method are proposed,in which the radial vibration of the blade tip in the BTC signals at different speeds is extracted and operated in the time domain to obtain the rotor unbalanced vibration,the signal is reconstructed,and cross-correlation analysis is used to accurately identify the magnitude and phase of the unbalanced signal.Finally,a rotor test bench is utilized for experimental verification.The results reveal that the dynamic balancing method based on the BTC signal can more precisely identify the rotor unbalance than the traditional rotor dynamic balancing method.The application of this technique will effectively improve engine health management and fault prediction.
基金the National Natural Science Foundation of China(Nos.T2322004 and 22078066)。
文摘Currently,it is still a challenge to develop an organic photosensitizer(PS)with outstanding near-infrared absorption,low O2dependence,precise tumor targeting and rapid clearance through the kidney to improve the overall outcome of phototherapy.In this study,we have designed an organic PS(Nc PB)with an excellent near-infrared light absorption through a refined molecular strategy.Meanwhile,Nc PB was assembled into nanoparticles with different sizes(Nano Nc PB-1 and Nano Nc PB-0)by a supramolecular modulation strategy.As the results,the nanoparticle with an ultra-small size(Nano Nc PB-1)generated a large number of superoxide anion(O_(2)^(·-))in a low-O_(2)-dependent manner and release plenty of heat.Furthermore,the results of in vivo experiments demonstrated that Nano Nc PB-1 actively accumulated in tumor tissues and showed a 92%tumor inhibition after photodynamic and photothermal combination therapy.More importantly,Nano Nc PB-1 could be rapidly cleared from the body of mice via the renal pathway,which alleviates potential side effects of prolonged retention of PS in the circulation.
文摘Combining practical engineering projects, this article analyzes the design strategies for the reconstruction and expansion of insufficient clearance sections in highway interchanges. This includes an overview of the project, a comparison of design options for insufficient clearance in interchanges, and the main design strategies for reconstruction and expansion. It is hoped that this analysis can provide a reference for the design of such road reconstruction and expansion projects.
文摘Metamorphic mechanism has the advantages of variable topology and variable degrees of freedom, which can realize the requirements of multi-conditions and multi-tasks, and has a good application prospect. The configuration transformation is prominent feature of the metamorphic mechanism. The number of constraints or properties of the kinematic pairs provided by the metamorphic kinematic pairs will change under certain conditions, its dynamic performance is much more complex than that of traditional kinematic pairs with immutable constraints. However, the clearance model about traditional kinematic pairs with immutable constraints established by long-term research is difficult to be directly applied to the metachromatic kinematic pairs. Referring to the experience of the traditional kinematic pairs with immutable constraints, the continuous contact model of Metamorphic Groove pin pair with clearance is established. According to the traditional continuous contact model of the kinematic pairs with immutable constraints, the forces between the elements of kinematic pair of the mechanism with clearance and the ideal mechanism without clearance are regarded as the same, and the inertia force and inertia moment of the components are also calculated according to the acceleration of the ideal mechanism. The clearance is regarded as a massless virtual bar with length r. For the rotating pair part, the massless virtual bar length r is the difference between the radius of the shaft and the hole, and for the sliding pair part, the massless virtual bar length r is half of the difference between the height of the slider and the guide groove. According to the new mechanism without gap after adding the imaginary bar, kinetic energy and potential energy of the system are calculated for the two configurations of mechanism with metamorphic Groove pin pair with clearance. The kinetic energy and potential energy of the system are calculated according to the new mechanism without clearance after adding the massless virtual bar. The kinetic energy, potential energy and generalized force are substituted into the Lagrangian equation to obtain the motion equation of the metamorphic mechanism, which lays the foundation for the dynamic performance study of the mechanism with metamorphic groove pin pair with clearance.
基金supported by National Natural Science Foundation of China(Grant No.92266201).
文摘As the performance of the box-type multiple launch rocket system(BMLRS)improves,its mechanical structures,particularly the plane clearance design between the slider on the rocket and the guide inside the launch canister,have grown increasingly complex.However,deficiencies still exist in the current launch modeling theory for BMLRS.In this study,a multi-rigid-flexible-body launch dynamics model coupling the launch platform and rocket was established using the multibody system transfer matrix method and the Newton-Euler formulation.Furthermore,considering the bending of the launch canister,a detection algorithm for slider-guide plane clearance contact was proposed.To quantify the contact force and friction effect between the slider and guide,the contact force model and modified Coulomb model were introduced.Both the modal and launch tests were conducted.Additionally,the modal convergence was verified.By comparing the modal experiments and simulation results,the maximum relative error of the eigenfrequency is 3.29%.thereby verifying the accuracy of the developed BMLRS dynamics model.Furthermore,the launch test validated the proposed plane clearance contact model.Moreover,the study investigated the influence of various model parameters on the dynamic characteristics of BMLRS,including launch canister bending stiffness,slider and guide material,slider-guide clearance,slider length and layout.This analysis of influencing factors provides a foundation for future optimization in BMLRS design.
文摘Advancements in murine modeling systems for ulcerative colitis have diversified our understanding of the pathophysiological factors involved in disease onset and progression.This has fueled the identification of molecular targets,resulting in a rapidly expanding therapeutic armamentarium.Subsequently,management strategies have evolved from symptomatic resolution to well-defined objective endpoints,including clinical remission,endoscopic remission and mucosal healing.While the incorporation of these assessment modalities has permitted targeted intervention in the context of a natural disease history and the prevention of complications,studies have consistently depicted discrepancies associated with ascertaining disease status through clinical and endoscopic measures.Current recommendations lack consideration of histological healing.The simultaneous achievement of clinical,endoscopic,and histologic remission has not been fully investigated.This has laid the groundwork for a novel therapeutic outcome termed disease clearance(DC).This article summarizes the concept of DC and its current evidence.
基金supported by the Natural Science Foundation of Hunan Province(2023JJ60087)the Clinical Medical Technology Innovation Guidance Project of Hunan Province(2021SK53501),China。
文摘Objective:Augmented renal clearance(ARC),in contrast to renal dysfunction,refers to enhanced renal elimination of circulating solutes compared to the expected baseline.Although patients may present with normal serum creatinine(Scr)levels,the incidence of ARC is high in intensive care unit(ICU)settings.ARC is associated with subtherapeutic exposure and treatment failure of renally cleared antibiotics.However,limited research exists on the incidence and risk factors of ARC in the ICU,and even fewer data are available specifically for neurological ICU(NICU).This study aims to determine the incidence and risk factors of ARC in neurocritically ill patients.Methods:We retrospectively analyzed all available Scr data of neurocritical care patients admitted to the NICU of the Second Xiangya Hospital of Central South University between December 2020 and January 2023.Creatinine clearance(CrCl)was calculated using the Cockcroft-Gault equation.ARC was defined as a CrCl≥130 mL/(min·1.73 m^(2))sustained for more than 50%of the duration of the NICU stay.A total of 208 neurocritically ill patients were assigned into an ARC group(n=52)and a non-ARC(N-ARC)group(n=156).Clinical characteristics were compared between the 2 groups.Variables with P<0.05 in univariate analysis were included in binary Logistic regression to identify independent risk factors for ARC.Results:The incidence of ARC among neurocritically ill patients was 25.00%.Of the 74 patients with normal CrCl,20(27.03%)gradually developed ARC during hospitalization.Compared with the N-ARC group,the patients of the ARC group were younger(P<0.001),with a higher proportion of females(P=0.048)and a lower admission mean arterial pressure(MAP)(P=0.034).Moreover,patients of the ARC group were commonly complicated with severe bacterial infections compared with the patients of the N-ARC group(P<0.001).In binary Logistic regression analysis,younger age(OR=0.903,95%CI 0.872 to 0.935)and severe bacterial infections(OR=6.270,95%CI 2.568 to 15.310)were significant predictors of ARC.Conclusion:ARC is relatively common in the NICU.A considerable number of patients with initially normal renal function developed ARC during hospitalization.Younger age and concurrent severe bacterial infection are important risk factors of ARC in neurocritically ill patients.
基金National Natural Science Foundation of China (10377011)
文摘This article describes the effects of some factors on the tip clearance flow in axial linear turbine cascades. The measurements of the total pressure loss coefficient are made at the cascade outlets by using a five-hole probe at exit Mach numbers of 0.10, 0.14 and 0.19. At each exit Mach number, experiments are performed at the tip clearance heights of 1.0%, 1.5%, 2.0%, 2.5% and 3.0% of the blade height. The effects of the non-uniform tip clearance height of each blade in the pitchwise direction are also studied. The results show that at a given tip clearance height, generally, total pressure loss rises with exit Mach numbers proportionally. At a fixed exit Mach number, the total pressure loss augments nearly proportionally as the tip clearance height increases. The increased tip clearance heights in the tip regions of two adjacent blades are to be blame for the larger clearance loss of the center blade. Compared to the effects of the tip clearance height, the effects of the exit Mach number and the pitchwise variation of the tip clearance height on the cascade total pressure loss are so less significant to be omitted.
基金Supported by National Natural Science Foundation of China(Grant Nos.51635002(Key Program),51605011,51275015)
文摘Joint clearances in antenna pointing mechanisms lead to uncertainty in function deviation. Current studies mainly focus on radial clearance of revolute joints, while axial clearance has rarely been taken into consideration. In fact, own?ing to errors from machining and assembly, thermal deformation and so forth, practically, axial clearance is inevitable in the joint. In this study, an error equivalent model(EEM) of revolute joints is proposed with considering both radial and axial clearances. Compared to the planar model of revolute joints only considering radial clearance, the journal motion inside the bearing is more abundant and matches the reality better in the EEM. The model is also extended for analyzing the error distribution of a spatial dual?axis("X–Y" type) antenna pointing mechanism of Spot?beam antennas which especially demand a high pointing accuracy. Three case studies are performed which illustrates the internal relation between radial clearance and axial clearance. It is found that when the axial clearance is big enough, the physical journal can freely realize both translational motion and rotational motion. While if the axial clearance is limited, the motion of the physical journal will be restricted. Analysis results indicate that the consideration of both radial and axial clearances in the revolute joint describes the journal motion inside the bearing more precise. To further validate the proposed model, a model of the EEM is designed and fabricated. Some suggestions on the design of revolute joints are also provided.
文摘Lateral clearance on the inside of horizontal curves is required by all geometric design guidelines in order to provide at least stopping sight distance. There already exist graphical models, analytical models, and design charts for determining minimum clearance offsets to meet the requirement. Some of these models determine the offsets based on constant design sight distance values on the assumption that drivers negotiate horizontal curves at constant speed. Therefore, those models are suitable for sites where there is no difference in speeds between tangent and curved sections. Past studies have reported that there are sites where drivers decelerate on entering horizontal curves and accelerate on departing from the curves. At those sites stopping sight distance for a given driver varies with driver location due to variable speed. This paper presents an analytical model and a chart for determining minimum offsets needed to provide desired sight distances at horizontal curves with variable operating speeds. At those sites the offsets yield roadside clearance boundaries that have transition arcs with performances that are similar to those of elliptical arcs. Therefore, practitioners may choose to use elliptical equations or equations and the chart developed herein. Results of this study will be of value to practitioners in the area of roadside design.
文摘Active control of turbine blade tip clearance continues to be a concern in design and control of gas turbines. Ever increasing demands for improved efficiency and higher operating temperatures require more stringent tolerances on turbine tip clearance. In this paper, a turbine tip clearance control apparatus and a model of turbine tip clearance are proposed; an implicit active generalized predictive control （GPC）, with auto-regressive （AR） error modification and fuzzy adjustment on control horizon, is presented, as well as a quantitative analysis method of robust per- turbation radius of the system. The active clearance control （ACC） of aero-engine turbine tip clear- ance is evaluated in a lapse-rate take-off transient, along with the comparative and quantitative analysis of the stability and robustness of the active tip clearance control system. The results show that the resultant active tip clearance control system with the improved GPC has favorable steadystate and dynamic performance and benefits of increased efficiency, reduced specific fuel consump- tion, and additional service life.
文摘Experiment and numerical simulation technique are used to investigate the tip leakage flow in an axial fan with tip clearance at the design condition. The flow field in the tip region of fan is measured using a PDA (Particle Dynamics Analysis) system. The flow is surveyed across the whole passage at fifteen axial locations (from the 100% axial chord in front of the leading edge to the 100% axial chord behind the trailing edge), mainly focusing on the outer 90% blade span. Both experiment measurement and numerical simulation indicates the leakage flow originated from the tip clearance along the chord rolls up into three dimensional spiral structure to form leakage flow vortex. The interaction of leakage flow and main flow will produce the low velocity zone, and block the flow. The leakage flow almost occupies the most part of flow passage behind the trailing edge.
文摘A centrifugal fan with the high speed and compact dimensions is studied numerically and experimentally. The centrifugal fan consists of a shrouded impeller rotating at 34 000 r/min with a small tip clearance 0.7 mm to the fixed outer casing. Computational models with/without the tip clearance are built and the κ-ω shear stress transport （SST） turbulence model and the unstructured mesh are applied to the numerical simulation for unsteady solutions. The overall performance is measured on a standard experimental bench and the major flow feature of each component inside the centrifugal fan is numerically investigated. In the presence of the tip clearance due to the difference of static pressure between leading and trailing edges of the clearance, i. e. , leading and trailing edges of the impeller, a strong return flow exists inside the clearance passage and re-circulates the main stream inside the impeller passage, and produces the strong flow interaction, thus changing the flow field and influencing the overall performance.
基金National Natural Science Foundation of China (59975076, 50905144)State Key Laboratory of Materials Processing and Die & Mould Technology, Huazhong University of Science and Technology (09-10)+1 种基金NPU Foundation for Fundamental Research (JC201028)Fund of the State Key Laboratory of Solidification Process-ing in NWPU
文摘Thin-walled tube numerical control （NC） bending is a tri-nonlinear physical process with multi-defect and multi-die constraints. The clearance on each contact interface is the major factor to indicate the contact conditions. A three-dimensional-finite element （3D-FE） model is established to consider the realistic dynamic boundary conditions of multiple dies under ABAQUS/Explicit platform. Combined with experiment, numerical study on bending behavior and bendability under different clearance between tube and various dies is conducted in terms of wrinkling, wall thinning and cross section deformation. The results show that （1）with smaller clearance of tube-wiper die and tube-mandrel, the wrinkling can be restrained while the wall thinning It and cross-section deformation Id increase; while excessive small clearance blocks tube materials to flow past tangent point and causes piles up, the onset of wrinkling enhances It and Id. （2）Both It and Id decrease with smaller clearance of tube-pressure die; the wrinkling possibility rises with larger clearance on this interface if the mandrel’s freedom along Y-axis is opened; smaller clearance of tube-bend die prevents wrinkling while increases It, and the clearance on this interface has little effect on Id. （3）A modified Yoshida buckling test （YBT） is used to address the wrinkling mechanisms under normal constraints in tube bending： the smaller clearance may restrain wrinkling efficiently; the smaller wall thickness, the less critical clearance needed; the critical clearance for tube bending 38 mm×1 mm×57 mm （tube outer diameter×wall thickness×centerline bending radius） equals about 20% of initial wall thickness.
基金the National Natural Science Foundation of China,No.31500650。
文摘BACKGROUND Nucleos(t)ide analog(NA)has shown limited effectiveness against hepatitis B surface antigen(HBsAg)clearance in chronic hepatitis B(CHB)patients.AIM To evaluate the efficacy and safety of add-on peginterferonα-2a(peg-IFNα-2a)to an ongoing NA regimen in CHB patients.METHODS In this observational study,195 CHB patients with HBsAg≤1500 IU/m L,hepatitis B e antigen(HBeAg)-negative(including HBeAg-negative patients or HBeAg-positive patients who achieved HBeAg-negative after antiviral treatment with NA)and hepatitis B virus-deoxyribonucleic acid<1.0×10^2 IU/mL after over 1 year of NA therapy were enrolled between November 2015 and December2018 at the Second Affiliated Hospital of Xi'an Jiaotong University,China.Patients were given the choice between receiving either peg-IFNα-2a add-on therapy to an ongoing NA regimen(add-on group,n=91)or continuous NA monotherapy(monotherapy group,n=104)after being informed of the benefits and risks of the peg-IFNα-2a therapy.Total therapy duration of peg-IFNα-2a was 48 wk.All patients were followed-up to week 72(24 wk after discontinuation of peg-IFNα-2a).The primary endpoint was the proportion of patients with HBsAg clearance at week 72.RESULTS Demographic and baseline characteristics were comparable between the two groups.Intention-to-treatment analysis showed that the HBsAg clearance rate in the add-on group and monotherapy group was 37.4%(34/91)and 1.9%(2/104)at week 72,respectively.The HBsAg seroconversion rate in the add-on group was 29.7%(27/91)at week 72,and no patient in the monotherapy group achieved HBsAg seroconversion at week 72.The HBsAg clearance and seroconversion rates in the add-on group were significantly higher than in the monotherapy group at week 72(P<0.001).Younger patients,lower baseline HBsAg concentration,lower HBsAg concentrations at weeks 12 and 24,greater HBsAg decline from baseline to weeks 12 and 24 and the alanine aminotransferase≥2×upper limit of normal during the first 12 wk of therapy were strong predictors of HBsAg clearance in patients with peg-IFNα-2a add-on treatment.Regarding the safety of the treatment,4.4%(4/91)of patients in the add-on group discontinued peg-IFNα-2a due to adverse events.No severe adverse events were noted.CONCLUSION Peg-IFNα-2a as an add-on therapy augments HBsAg clearance in HBeAg-negative CHB patients with HBsAg≤1500 IU/m L after over 1 year of NA therapy.
基金sponsored by Guangdong Science and Technology Project(No:2009B03081118)
文摘Objective:To explore the easily applicable indicators of practical value to evaluate the prognosis of acute respiratory distress syndrome（ARDS）.Methods:Blood and biochemical tests and bloodgas analyses were performed upon entry into the ICUs,12 h,24 h,48 h and 72 h after that in 72 ARDS patients（who were admitted to the ICUs of our hospital from January 2000 to December 2009）.Then APACHEⅡscores were achieved by combining relevant physiological parameters and laboratory results.Results:There was a statistical difference between the death group and survival group at different time points upon entering the ICUs in terms of APACHEⅡscore, alveolar-arterial oxygen difference and arterial blood lactate clearance rate.PaO<sub>2</sub>/FiO<sub>2</sub> values were recorded to be statistically different between the death group and survival group 24 h,48 h and 72 h,respectively after entry into the ICUs.In addition,registered linear regression existed between APACHEⅡscore,alveolar-arterial oxygen difference or PaO<sub>2</sub>/FiO<sub>2</sub> value and time. APACHEⅡscore 24 h and 72 h after entering ICUs predicted mortality with an area under the ROC curve（AUC） standing respectively at 0.919 and 0.9SS.Arterial blood lactate clearance rate 12 h, 24 h,48 h and 72 h after entering ICUs predicted mortality with an area under the ROC curve （AUC） at 0.918,0.918,0.909 and 0.991,respectively.Conclusions:APACHEⅡscore applied in combination with arterial blood lactate clearance rate is of clinical significance in assessing the prognosis of ARDS patients.
基金Supported by National Natural Science Foundation of China(Grant Nos.51205121,51375162)Scientific Research Foundation of Hunan Provincial Education Department of China(Grant No.13A023)Postgraduate Innovation Foundation of Hunan University of Science and Technology,China(Grant No.S140020)
文摘The inner and outer oil film dynamic characteristic coefficients of floating ring bearings（FRBs） change due to the manufacturing tolerance of the floating ring, journal and intermediate, which leads to high-speed turbocharger＇s vibration too large and even causes nonlinear vibration accident. However, the investigation of floating ring bearing manufacturing tolerance clearance on the rotordynamic characteristics is less at present. In order to study the influence law of inner and outer clearance on turbocharger vibration, the rotor dynamic motion equations of turbocharger supported in FRBs are derived by analyzing the size relations between floating ring, journal and intermediate for the inner and outer oil film clearances, the time transient response analysis for combination of FRBs clearance are developed. A realistic turbocharger is taken as a research object, the FE model of the turbocharger with FRBs is modeled. Under the conditions of four kinds of limit state bearing clearances for inner and outer oil film, the nonlinear transient analyses are performed based on the established FE dynamic models of the nonlinear rotor-FRBs system applied incentive combinations of gravity and unbalance force, respectively. From the waterfall, the simulation results show that the speed for the appearance of fractional frequency is not identical and the amplitude magnitude is different under the four kinds of bearing manufacturing tolerance limit clearances, and fractional frequency does not appear in the turbocharger and the amplitude is minimum under the ODMin/IDMax bearing manufacturing tolerance clearances. The turbocharger vibration is reduced by controlling the manufacturing tolerance clearance combinations of FRBs, which is helpful for the dynamic design and production-manufacturing of high-speed turbocharger.
基金supported by a grant from the Foundation of the Ministry of Health,China(2008ZX1005)
文摘BACKGROUND: Acute liver failure(ALF) is an acute severe deterioration of liver function with high mortality. Early and accurate prognostic assessment of patients with ALF is critically important. Although the model for end-stage liver disease(MELD) scores and King’s College Hospital(KCH) criteria are well-accepted as predictive tools, their accuracy is unsatisfactory.The indocyanine green(ICG) clearance test(ICGR15, ICG retention rate at the 15 minutes) is a sensitive indicator of liver function. In this study, we investigated the efficacy of the ICGR15 for the short-term prognosis in patients with ALF. We compared the predictive value of ICGR15 with the MELD scores and KCH criteria.METHODS: Sixty-nine patients who had been diagnosed with ALF were recruited retrospectively. ICGR15 had been performed by ICG pulse spectrophotometry and relevant clinical and laboratory indices were analyzed within 24 hours of diagnosis.In addition, the MELD scores and KCH criteria were calculated.RESULTS: The three-month mortality of all patients was 47.83%.Age, serum total bilirubin and creatinine concentrations,international normalized ratio for prothrombin time, ICGR15,MELD scores and KCH criteria differed significantly between surviving and deceased patients. A positive correlation was observed between ICGR15 and MELD scores(r=0.328, P=0.006).The ICGR15-MELD model, Logit(P)=0.096×ICGR15+0.174 ×MELD score–9.346, was constructed by logistic regression analysis. The area under the receiver operating characteristic curve was 0.855. When set the cut-off point to-0.4684, the sensitivity was 87.90% and specificity, 72.20%. The area under the receiver operating characteristic curve of the ICGR15-MELD model(0.855) was significantly higher than that of the ICGR15(0.793), MELD scores(0.776) and KCH criteria(0.659).Based on this cut-off value, the patients were divided into two groups. The mortality was 74.36% in the first group(ICGR15-MELD≥-0.4686) and 13.33% in the second group(ICGR15-MELD<-0.4686), with a significant difference between the two groups(χ2=25.307, P=0.000).CONCLUSION: The ICGR15-MELD model is superior to the ICGR15, MELD scores, and KCH criteria in predicting the shortterm prognosis of patients with ALF.
