Liver as a new target organ in Alzheimer's disease:insight from cholesterol metabolism and its role in amyloid-beta clearance

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.

Disease clearance in ulcerative colitis:A new therapeutic target for the future

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.

The Risk Factors of Lymphedema in Breast Cancer Patients Post Axillary Clearance

Introduction: Breast cancer is the number one malignancy affecting females in Saudi Arabia with a prevalence of 22.4%. Breast cancer incidence increases annually due to the aid of established screening programs, leading to the discovery of breast cancer in its early stages. Surgical treatment is an integral part of early breast cancer management to achieve local control. Axillary surgical interventions such sentinel lymph node biopsy (SLNB) and axillary lymph node clearance (ALND) aim to stage the axilla as an adjunct to the management of the primary breast tumor. In this paper, we reviewed female breast cancer patients aged 30 - 60 who underwent surgical treatment of SLNB and/or ALND with reporting the prevalence of lymphedema and other associated complications and risk factors. Methodology: A cross-sectional non-interventional study, with a sample size of 250 including breast cancer cases from 2016 to 2019 at National Guard Hospital (NGH) in Jeddah, Saudi Arabia. Results: A total of 253 breast cancer cases were included in this study, with a mean age of 53 years, 52.7% were postmenopausal and positive family history was present among 21% of cases. Further, 90.9% of the cases had unilateral disease. Staging was as follows: stage I 14.5%, stage II 45.2%, stage III 37.1%, and stage IV 3.2%. Mastectomy was done in 73.4% cases and lumpectomy was performed in 34.1% of cases. In addition, 93.3% of patients had SLNB and 49% of them were positive. Axillary dissection was performed in 69.6% of our patients. Radiotherapy and chemotherapy were given to 71.8% and 80.4% of cases respectively. Among the chemotherapy (chemo) recipients, 40.2% received adjuvant chemo, 54.5% received neoadjuvant chemo, and the remaining 5.3% received both. Further, the most prevalent complication was pain accounting for 42.1% of total complications, and the least prevalent was cellulitis 4%. Also, seroma developed in 18.3% cases, paresthesia noted in 5.6% of cases, winged scapula was reported as 2%, weakness and necrosis were seen in 6% and 13.1% of cases respectively. Axillary vein thrombosis and lymphangiosarcoma were reported in none of the patients (0%). Lymphoedema accounted for 16.1% of overall complications, 85% of the patients who developed lymphedema had undergone ALND, and 12.9% and 14.4% received radiotherapy and chemotherapy respectively. Lymphedema was observed in breast cancer stages as follows: stage I 1.2%, stage II 7.2%, and stage III 5.2%. Patients with body mass index (BMI) of 30 - 39 kg/m2 had 7.2% prevalence of lymphedema compared to other BMI groups. Overall mortality was 8.3%. Conclusion: The findings of our study suggest that the prevalence of lymphedema was higher in ALND patients with locally advanced tumors, and higher BMI, compared to patients with stage I breast cancer and low BMI. Further, the prevalence of lymphedema in patients who underwent ALND was significantly lower than those who were treated by lumpectomy 10.3% (p-value = 0.034) in comparison to mastectomy 19.3%.

Traffic Incident Management Performance Measures: Ranking Agencies on Roadway Clearance Time

This study develops a procedure to rank agencies based on their incident responses using roadway clearance times for crashes. This analysis is not intended to grade agencies but to assist in identifying agencies requiring more training or resources for incident management. Previous NCHRP reports discussed usage of different factors including incident severity, roadway characteristics, number of lanes involved and time of incident separately for estimating the performance. However, it does not tell us how to incorporate all the factors at the same time. Thus, this study aims to account for multiple factors to ensure fair comparisons. This study used 149,174 crashes from Iowa that occurred from 2018 to 2021. A Tobit regression model was used to find the effect of different variables on roadway clearance time. Variables that cannot be controlled directly by agencies such as crash severity, roadway type, weather conditions, lighting conditions, etc., were included in the analysis as it helps to reduce bias in the ranking procedure. Then clearance time of each crash is normalized into a base condition using the regression coefficients. The normalization makes the process more efficient as the effect of uncontrollable factors has already been mitigated. Finally, the agencies were ranked by their average normalized roadway clearance time. This ranking process allows agencies to track their performance of previous crashes, can be used in identifying low performing agencies that could use additional resources and training, and can be used to identify high performing agencies to recognize for their efforts and performance.

Predictive Value of Serum pgRNA on HBeAg Clearance in Patients with Chronic Hepatitis B with Low HBeAg Levels Treated with Pegylated Interferon

Objective:To study the predictive value of serum pregenomic RNA(pgRNA)on HBeAg clearance in patients with chronic hepatitis B with low HBeAg levels during pegylated interferon therapy.Methods:Twenty chronic hepatitis B patients with HBeAg positive and quantitative<50S/CO were selected for this study.The subjects underwent pegylated interferon therapy for 48-96 weeks and were followed up in the outpatient clinic after treatment.The patients were then divided into groups based on whether their HbeAg turned negative.The predictive ability of each indicator for HBeAg negative conversion was evaluated in the HBeAg negative group and the HBeAg positive group.Results:The results of logistic regression analysis suggested that pgRNA and HBcrAg were better indicators for predicting the clearance of HBeAg after treatment.Conclusion:For patients with chronic hepatitis B with low HBeAg levels,pgRNA is a good indicator in predicting HBeAg clearance during pegylated interferon therapy.

Experimental Study of the Motion Modes of a Planar Mechanical System with Multi-Clearance Revolute Joints

Clearances in joints of a mechanical multibody system can induce impulsive forces, leading to vibrations that compromise the system’s reliability, stability, and lifespan. Through dynamic analysis, designers can investigate the effects of the clearances on the dynamics of the multibody system. A revolute joint with clearance exhibits three motions which are;free-flight, impact and continuous contact motion modes. Therefore, a multibody system with n-number of revolute clearance joints will exhibit 3n motion modes which are a combination of the three motions in each joint. This study investigates experimentally the nine motion modes in a mechanical system with two revolute clearance joints. A slider crank mechanism has been used as the demonstrative example. We observed that the experimental curve exhibits a greater impact compared to the simulation curve. In conclusion, this experimental investigation offers valuable insights into the dynamics of planar mechanical systems with multiple clearance revolute joints. Utilizing a slider-crank mechanism for data acquisition, the study successfully confirmed seven out of nine motion modes previously identified in numerical research. The missing modes are attributed to inherent complexities in real-world systems, such as journal-bearing misalignment.

An Error Equivalent Model of Revolute Joints with Clearances for Antenna Pointing Mechanisms

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.

Minimum Clearance Offsets for Providing Desired Stopping Sight Distances at Simple Curves with Variable Operating Speeds

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.

Combined APACH Ⅱ score and arterial blood lactate clearance rate to predict the prognosis of ARDS patients

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.PaO2/FiO2 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 PaO2/FiO2 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.

Effects of Floating Ring Bearing Manufacturing Tolerance Clearances on the Dynamic Characteristics for Turbocharger

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.

Add-on pegylated interferon augments hepatitis B surface antigen clearance vs continuous nucleos(t)ide analog monotherapy in Chinese patients with chronic hepatitis B and hepatitis B surface antigen≤1500 IU/mL:An observational study

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.

Indocyanine green clearance test combined with MELD score in predicting the short-term prognosis of patients with acute liver failure

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.

Effects of Semi-floating Ring Bearing Outer Clearance on the Subsynchronous Oscillation of Turbocharger Rotor

Semi-floating ring bearing（SFRB） is developed to control the vibration of turbocharger rotor. The outer clearance of SFRB affects the magnitude and frequency of nonlinear whirl motion, which is significant for the design of turbocharger. In order to explore the effects of outer clearance, a transient finite element analysis program for rotor and oil film bearing is built and validated by a published experimental case. The nonlinear dynamic behaviors ofrotor-SFRB system are simulated. According to the simulation results, two representative subsynchronous oscillations excited by the two hearings respectively are discovered. As the outer clearance of SFRB increases from 24 ~tm to 60 pro, the low-frequency subsynchronous oscillation experiences three steps, including a strong start, a gradual recession and a combination with the other one. At the same time, the high-frequency subsynchronous oscillation starts to appear gradually, then strengthens, and finally combines. If gravity and unbalance are neglected, the combination will start starts from high rotor speed and extents to low rotor speed, just like a ＂zipper＂. It is found from the quantitative analysis that when the outer clearance increases, the vibration amplitude experiences large value firstly, then reduction, and suddenly increasing after combination. A useful design principle of SFRB outer clearance for minimum vibration amplitude is proposed： the outer clearance value should be chosen to keep the frequency of two subsynchronous oscillations clearly separated and their amplitudes close.

Clearance Influence on Dynamic Response of Intermittent Roller Chain Drive

The clearances appear in chain link hinges induced by manufacturing tolerance or wear of components are the most important factor that influences the dynamic performance of the intermittent roller chain drives. Due to the existence of the clearances in chain link hinges, the serious impact vibration phenomenon which influences the stability and the position accuracy of the chain drive system would be caused in the intermittent motion. But, the problem may be that a reasonable modeling on the chain with clearances is difficult due to the large clearance＇s number in chain system and the fact that the clearance＇ size are different. Currently, the studies on the dynamics of the intermittent roller chain considering the multi-clearance＇ joints are rare. Most research works have only focused on the constant moving chains. Taking the intermittent roller chain system as an object, this paper designs and builds the experimental device of this kind of mechanical system. The Longitudinal vibration response of the intermittent chain under the different motion laws was tested. The experimental study shows that the clearances presented in chain link hinges can cause severe impact vibration in the intermittent motion of chain. In subsequent work, the dynamic model of the intermittent roller chain system with the multi-clearance＇ joints was established. By calculating the dynamic response of this kind of mechanical system under the different motion laws, the effect of the clearances on the dynamic response of the intermittent chain drive system was analyzed. The theoretical simulation shows that the serious impact vibration phenomenon of the chain system can be caused by the clearances at the start accelerating period, and the chain drive system is often accompanied by the severe shock and vibration at the moment that the chain moves from the acceleration period to deceleration period. The research conclusions made by the experimental and theoretical studies indicate that the use of motion laws with small and continuous jerk at conversion point can effectively suppress the impact vibration at this point caused by clearances＇ effect. Additionally, the use of nonsymmetrical motion laws with small jerk approaching the end of the indexing period can obtain a smaller residual vibration. The presented motion law can provide an important reference for the improvement of the dynamic performance of the intermittent chain drive systems.

Numerical Analysis of Nozzle Clearance's Effect on Turbine Performance

Variable nozzle turbine （VNT） has become a popular variable geometry turbine （VGT） technology for the diesel engine application. Nozzle clearance, which can＇t be avoided on the hub and shroud side of the VNT turbine due to the pivoting stators, can lead to turbine performance deterioration. However, its mechanism is still not clear. In this paper, numerical investigation, which is validated by experiment, is carried out to study the mechanism of the nozzle clearance＇s effect on the turbine performance. Firstly, performance of the mixed flow turbine with fixed nozzle clearances tested on flow bench. Performance of the tested turbine with the same nozzle clearance is numerically simulated. The numerical result agrees well with the test data, which proves correct of the numerical method. Then the turbine performance with different nozzle clearances is numerically analyzed. The research showed that with nozzle clearance, flow loss in the nozzle increases at first and it reaches the maximum value when the clearance ratio is 5%. Flow at the exit of the nozzle becomes less uniform with nozzle clearance. The negative incidence angle of the rotor also increases with nozzle clearance and leads to more incidence angle loss in the rotor. The low energy fluid formed in the nozzle due to the nozzle clearance migrates from hub to shroud side in the rotor, which is another main reason for the rotor＇s performance degradation. The present research exposed the mechanism of the dramatically decrease of the turbine performance with nozzle clearance： （a） The loss associated with the nozzle leakage increases with the nozzle clearance; （b） The flow loss grows up quickly in the rotor due to the incidence angle loss and migration of the low energy fluid from hub to shroud side.

Induced dural lymphangiogenesis facilities soluble amyloid-beta clearance from brain in a transgenic mouse model of Alzheimer's disease

Impaired amyloid-β clearance from the brain is a core pathological event in Alzheimer＇s disease.The therapeutic effect of current pharmacotherapies is unsatisfactory,and some treatments cause severe side effects.The meningeal lymphatic vessels might be a new route for amyloid-β clearance.This study investigated whether promoting dural lymphangiogenesis facilitated the clearance of amyloid-β from the brain.First,human lymphatic endothelial cells were treated with 100 ng/m L recombinant human vascular endothelial growth factor-C（rh VEGF-C） protein.Light microscopy verified that rh VEGF-C,a specific ligand for vascular endothelial growth factor receptor-3（VEGFR-3）,significantly promoted tube formation of human lymphatic endothelial cells in vitro.In an in vivo study,200 μg/m L rh VEGF-C was injected into the cisterna magna of APP/PS1 transgenic mice,once every 2 days,four times in total.Immunofluorescence staining demonstrated high levels of dural lymphangiogenesis in Alzheimer＇s disease mice.One week after rh VEGF-C administration,enzyme-linked immunosorbent assay results showed that levels of soluble amyloid-β were decreased in cerebrospinal fluid and brain.The Morris water maze test demonstrated that spatial cognition was restored.These results indicate that the upregulation of dural lymphangiogenesis facilities amyloid-β clearance from the brain of APP/PS1 mice,suggesting the potential of the VEGF-C/VEGFR-3 signaling pathway as a therapeutic target for Alzheimer＇s disease.

Enzyme-digested Colla Corii Asini(E’jiao) prevents hydrogen peroxide-induced cell death and accelerates amyloid beta clearance in neuronal-like PC12 cells

As an aging-associated degenerative disease,Alzheimer’s disease is characterized by the deposition of amyloid beta(Aβ),oxidative stress,inflammation,dysfunction and loss of cholinergic neurons.Colla Corii Asini(CCA)is a traditional Chinese medicine which has been used for feebleness-related diseases and anti-aging.CCA might delay aging-induced degenerative changes in neurons.In the present study,we evaluated antioxidant activity,cytoprotective effects,and Aβremovability of enzyme-digested Colla Corii Asini(CCAD).Oxygen radical absorbance capacity(ORAC)activity assay showed that,as compared to gelatins from the skin of porcine,bovine and cold water fish,CCA exhibited the highest ORAC activity.The ORAC activity of CCA and CCAD was increased gradually by the length of time in storage.Ultrastructure analysis by scanning electron microscopy showed that among CCA manufactured in 2008,2013,2017 and gelatin from cold water fish skin,CCA manufactured in 2008 presented the smoothest surface structure.We further tested the protective effects of CCAD(manufactured in 2008)and enzyme-digested gelatin from cold water fish skin(FGD)on hydrogen peroxide(H2O2)-induced cell death in nerve growth factor-differentiated neuronal-like PC12 cells.Presto blue assay showed that both FGD and CCAD at 0.5 mg/m L increased cell viability in H2O2-treated neuronal-like PC12 cells.The protection of CCAD was significantly superior to that of FGD.Acetylcholinesterase(Ach E)assay showed that both FGD and CCAD inhibited Ach E activity in nerve growth factor-differentiated neuronal-like PC12 cells to 89.1%and 74.5%of that in non-treated cells,respectively.The data suggest that CCAD might be able to increase the neurotransmitter acetylcholine.Although CCAD inhibited Ach E activity in neuronal-like PC12 cells,CCAD prevented H2O2-induced abnormal deterioration of Ach E.ELISA and neprilysin activity assay results indicated that CCAD reduced amyloid beta accumulation and increased neprilysin activity in Aβ1–42-treated neuronal-like PC12 cells,suggesting that CCAD can enhance Aβclearance.Our results suggest that CCA might be useful for preventing and treating Alzheimer’s disease.

Indocyanine green clearance in evaluating the recovery of liver reserve function after superselective transarterial chemoembolization

Transarterial chemoembolization(TACE)may ravage normal liver tissues apart from the neoplastic nodules which offset the anti-tumor effect.This study aimed to evaluate the recovery of liver reserve function(LRF)after TACE by indocyanine green(ICG)clearance test and other routine liver function tests.Forty-six newly diagnosed HCC patients who had undergone TACE as the initial treatment from January 2011 to January 2012 were enrolled in this study.The effects of age,basic ICG clearance rate and interval time between two assessments on the recovery of LRF were analyzed.We found that ICG retention rate at the 15 minutes(ICGR15)was significantly increased after TACE(12.3±8.1%vs 16.8±12.1%,P【0.01)in all the 46 patients.In particular,the ICGR15 value was increased in older patients(age】55 years,20.3±12.5%vs 13.7±7.2%,P【0.01).The interval of ICG test also affected the ICGR15 value(≤47days,17.8±11.4%after vs 12.1±7.1%before TACE,P【0.01).Our data suggested that TACE decreased LRF,especially in older patients.ICG test was more sensitive to evaluate the recovery of LRF after TACE than the Child-Pugh grade and routine liver function tests.

HBsAg clearance by Peg-interferon addition to a long-term nucleos(t)ide analogues therapy

The ideal endpoint of hepatitis B virus(HBV)antiviral therapy is HBsAg loss,a difficult goal to obtain,especially in HBeAg negative patients.Herein,we report the results obtained by the addition of peg-interferonα-2a to a long-lasting nucleos(t)ide analogues therapy in a HBeAg negative,genotype D patient with steadily HBV-DNA negative/HBsAg positive values.In 2002,our Caucasian 44-year-old male patient received lamivudine and,4 years later,added adefovir because of a virological breakthrough.In 2011,considering his young age,liver stiffness(4.3 kPa)and HBsAg levels(3533IU/mL),we added Peg-interferonα-2a for six months(3in combination with nucleos(t)ide analogues followed by 3 mo of Peg-interferonα-2a monotherapy).A decrease of HBsAg levels was observed after 1 mo(1.21log)of Peg-interferon and 3 mo(1.88 log)after the discontinuation of all drugs.Later,a complete clearance of HBsAg was obtained with steadily undetectable HBVDNA serum levels(<9 IU/mL).HBsAg clearance by the addition of a short course of Peg-interferonα-2a represents an important result with clinical and pharmacoeconomic implications,considering that nucleos(t)ide analogues therapy in HBeAg negative chronic hepatitis B patients is considered a long-lasting/life-long treatment.

COMPARISON OF TWO METHODS TO INCREASE TIP CLEARANCE AND ITS EFFECT ON PERFORMANCE OF TURBOCHARGER CENTRIFUGAL COMPRESSOR STAGE

Tip clearance between the blade tip and casing of a centrifugal compressor can be varied through two methods： by changing the blade height （MI） or by changing the casing diameter （M2）. Numerical simulations are carried out to compare these two methods and their effect on the stage and impeller performance. The impeller and diffuser are connected through rotor stator boundary using frozen rotor approach. Overall stage performance and the flow configuration have been investigated for nine tip clearance levels from no gap to 1 mm. Impeller and diffuser performances are also presented separately. It has been found that the overall and impeller performance are comparatively better for MI below tip clearance of 0.5 mm whereas M2 is found advantageous above 0.5 mm of tip clearance. Both MI and M2 show performance degradation with the increase in tip clearance. Two models have been proposed for the stage total pressure ratio and efficiency, which are found to be in agreement with experimental results. The impeller efficiency and the pressure ratio are found to be maximum at tip clearance of 0.1 mm for both the cases however minimum diffuser effectiveness is also observed at the same clearance level. Diffuser effectiveness is found to be maximum at zero gap for both cases. As it is practically impossible to have zero gap for unshrouded impellers so it is concluded that the optimum thickness is 0.5 mm onwards for MI and 0.5 mm for M2 in terms of diffuser effectiveness. Mass averaged flow parameters, entropy, blade loading diagram and relative pressure fields are presented, showing the loss production within the impeller passage with tip clearance.