BACKGROUND Nonalcoholic fatty liver disease(NAFLD)is the most common chronic liver disea-se.The accuracy of noninvasive biomarkers for detecting hepatic steatosis is still limited.AIM To assess the diagnostic performa...BACKGROUND Nonalcoholic fatty liver disease(NAFLD)is the most common chronic liver disea-se.The accuracy of noninvasive biomarkers for detecting hepatic steatosis is still limited.AIM To assess the diagnostic performance of noninvasive steatosis biomarkers in diag-nosing NAFLD using magnetic resonance imaging proton density fat fraction(MRI-PDFF)as the gold standard.METHODS A total of 131 suspected NAFLD patients(60%male,median age 36 years)under-going MRI-PDFF were consecutively recruited from a tertiary hospital.Steatosis grades determined by MRI-PDFF were classified as none(<5%),mild(5%-11%),moderate(11%-17%),and severe(≥17%).Six steatosis biomarkers were calculated according to clinical parameters and laboratory tests,including fatty liver index,hepatic steatosis index,ZJU index,Framingham steatosis index,triglycerides and glucose index,and visceral adiposity index.The accuracy of these biomarkers in detecting hepatic steatosis was evaluated using the area under the receiver operating characteristic curves(AUCs).The Youden index was used to determine the optimal cut-off for each biomarker.The linear trend analysis of each biomarker across the steatosis grades was conducted by Mantel-Haenszelχ2 test.Spearman's rank correlation assessed the relationship between steatosis biomarkers and MRI-PDFF.RESULTS Steatosis grades based on MRI-PDFF prevalence were:None 27%,mild 40%,moderate 15%and severe 18%.Six steatosis biomarkers showed a linear trend across the steatosis grades and a significant positive correlation with MRI-PDFF.The six steatosis biomarkers demonstrated AUCs near 0.90(range:0.857-0.912,all P<0.001)for diagnosing NAFLD by MRI-PDFF≥5%.The optimal cut-offs showed sensitivity between 84.4%-91.7%and specificity between 71.4%-85.7%.The diagnostic performance of these biomarkers in detecting moderate-to-severe and severe steatosis was relatively weaker.CONCLUSION These noninvasive steatosis biomarkers accurately diagnosed NAFLD and correlated well with MRI-PDFF for detecting NAFLD,but they did not effectively detect moderate or severe steatosis.展开更多
A new model on predicting the density of hot-rolled multi-phased medium-Mn steel has been presen ted on the basis of thermodynamic calculations. This is an integrated model, which includes one for calculating the reta...A new model on predicting the density of hot-rolled multi-phased medium-Mn steel has been presen ted on the basis of thermodynamic calculations. This is an integrated model, which includes one for calculating the retained austenite （RA） fraction and the other for volume expansion during the aus tenite-to martensite transformation, because both of them are key parameters for calculating the den- sity of steel at ambient temperature. The existing empirical equations for calculating Mx temperature and lattice constants of both martensite and austenite have been all rcassessed by the XRD measure ments on the microstructures of seven hot-rolled medium-Mn steels. Finally, the densities ot seven steels were calculated merely from compositions and compared with the measured ones. The differ ence between them is no more than 1 %, suggesting that the presented model should be of good value in designing the low density steels.展开更多
Estimating the Probability Density Function（PDF） of the performance function is a direct way for structural reliability analysis,and the failure probability can be easily obtained by integration in the failure domai...Estimating the Probability Density Function（PDF） of the performance function is a direct way for structural reliability analysis,and the failure probability can be easily obtained by integration in the failure domain.However,efficiently estimating the PDF is still an urgent problem to be solved.The existing fractional moment based maximum entropy has provided a very advanced method for the PDF estimation,whereas the main shortcoming is that it limits the application of the reliability analysis method only to structures with independent inputs.While in fact,structures with correlated inputs always exist in engineering,thus this paper improves the maximum entropy method,and applies the Unscented Transformation（UT） technique to compute the fractional moments of the performance function for structures with correlations,which is a very efficient moment estimation method for models with any inputs.The proposed method can precisely estimate the probability distributions of performance functions for structures with correlations.Besides,the number of function evaluations of the proposed method in reliability analysis,which is determined by UT,is really small.Several examples are employed to illustrate the accuracy and advantages of the proposed method.展开更多
Purpose: Bone marrow and muscle adiposity have been considered to correlate with osteoporosis and Sarcopenia. Proton Density Fat Fraction (PDFF) can be measured by Magnetic Resonance Imaging (MRI). The purpose of the ...Purpose: Bone marrow and muscle adiposity have been considered to correlate with osteoporosis and Sarcopenia. Proton Density Fat Fraction (PDFF) can be measured by Magnetic Resonance Imaging (MRI). The purpose of the present study was to measure PDFF in the lumbar spine, paraspinal muscle and subcutaneous fat tissue. Methods: Participants were comprised of 30 patients (18 males, 12 females;age range, 14 - 87 years) who underwent MRI due to low back symptoms. PDFFs for the body of the fourth lumbar vertebra (L4), paraspinal muscle, and subcutaneous fat were measured. Results: PDFFs of the vertebral body and subcutaneous fat were significantly higher than that of paraspinal muscle (p < 0.001). PDFF was significantly higher for subcutaneous fat than for the vertebral body (p < 0.001). Although no significant differences in PDFF of the vertebral body, paraspinal muscle, and subcutaneous fat between females and males, PDFFs of the vertebral body and paraspinal muscle were significantly higher in older subjects (>63 years) than in younger subjects (Conclusions: PDFF of the vertebral body was significantly higher than that of paraspinal muscle. PDFFs of the vertebral body and paraspinal muscle were significantly lower in younger subjects than in older subjects.展开更多
The accumulation of soil organic carbon(SOC)and total nitrogen(TN)is easily accomplished by returning crop straw,which strongly affects the formation and pore structure of aggregates,especially in black soil.We return...The accumulation of soil organic carbon(SOC)and total nitrogen(TN)is easily accomplished by returning crop straw,which strongly affects the formation and pore structure of aggregates,especially in black soil.We returned maize straw at different rates(6,000,9,000,12,000 and 15,000 kg ha^(-1))for nine years to investigate its influence on the SOC and TN contents in the SOC fractions of aggregates by combining size and density fractionation.Their subsequent influences on pore morphology and size distribution characteristics were examined using X-ray microcomputed tomography scanning(μCT).The results showed that returning straw significantly increased the contents of C and N in the SOC fractions of aggregates,especially at the return rates of 12,000 and 15,000 kg ha^(-1),which in turn promoted aggregate formation and stability,and ultimately amended pore structure.The pore size>100μm,porosity(>2μm),and morphological characteristics(anisotropy,circularity,connectivity and fractal dimension)significantly increased,but the total number of pores significantly decreased(P<0.05).Our results indicated that the amendment of the pore morphology and size distribution of soil aggregates was primarily controlled by the higher contents of C and N in the density fractions of aggregates,rather than in the aggregate sizes.Furthermore,this pore network reconfiguration favored the storage of C and N simultaneously.The findings of this study offer valuable new insights into the relationships between C and N storage and the pore characteristics in soil aggregates under straw return.展开更多
The importance of soil organic carbon （SOC） under forests in the global carbon cycle depends on the stability of the soil carbon and its availability to soil microbial biomass. We investigated the effects of success...The importance of soil organic carbon （SOC） under forests in the global carbon cycle depends on the stability of the soil carbon and its availability to soil microbial biomass. We investigated the effects of successive rotations of Chinese fir （Cunninghamia lanceolata （Lamb.） Hook） plantations on the stability of SOC and its availability to microbes by adopting the two-step hydrolysis with H2SO4 and density fractionation. The results showed that successive rotations of Chinese fir decreased the quantity of total SOC, recalcitrant fraction, and carbohydrates in Labile Pool I （LPI）, and microbial properties evidently, especially at 0-10 cm horizon. However, cellulose included in Labile Pool Ⅱ （LP Ⅱ） and the cellulose/total carbohydrates ratio increased in successive rotations of Chinese fir. The noncellulose of carbohydrates included in LPI maybe highly available to soil microbial biomass. Hence the availability of SOC to microbial biomass declined over the successive rotations. Although there was no significant change in recalcitrance of SOC over the successive rotations of Chinese fir, the percentage of heavy fraction to total SOC increased, suggesting that the degree of physical protection for SOC increased and SOC became more stable over the successive rotations. The degradation of SOC quality in successive rotation soils may be attributed to worse environmental conditions resulted from disturbance that related to ＂slash and burn＂ site preparation. Being highly correlated with soil microbial properties, the cellulose/total carbohydrates ratio as an effective indicator of changes in availability of SOC to microbial biomass brought by management practices in forest soils.展开更多
Forest management practices such as prescribed burning and thinning in forest ecosystems may alter the properties of soil organic matter （SOM）. In this study, surface softs from field plots in the Bankhead National ...Forest management practices such as prescribed burning and thinning in forest ecosystems may alter the properties of soil organic matter （SOM）. In this study, surface softs from field plots in the Bankhead National Forest, Alabama, USA, were used to investigate possible SOM transformations induced by thinning and burning. Elemental analysis and solid-state 13C cross polarization magic angle spinning nuclear magnetic resonance （13C CPMAS NMR） spectroscopy were used to characterize SOM fractions in whole soils, humic substances, and density fractions. Our data revealed that the changes in SOM fractions due to the repeated burning carried out in the forest ecosystem studied were involved mainly with alkyl C, O-alkyl C, and carbohydrate functional groups, implying that most prominent reactions that occurred involved dehydrogenation, de-oxygenation, and decarboxylation. In addition, burning and thinning might have also affected the distribution and composition of free and occluded particulate SOM fractions. The limited structural changes in SOM fractions suggested that low-intensity prescribed fire in the forest ecosystem studied will not create major structural changes in SOM fractions.展开更多
Insight into the carbon turnover in soil aggregates and density fractions is essential for reducing the uncertainty in estimating carbon pools on the Tibetan Plateau,and how they vary with land use type is unclear.In ...Insight into the carbon turnover in soil aggregates and density fractions is essential for reducing the uncertainty in estimating carbon pools on the Tibetan Plateau,and how they vary with land use type is unclear.In this study,the effect of land use type on carbon storage and fractionation was quantified based on organic carbon and its ^(13)C abundance at the microscale of soil aggregates and density fractions in Tibetan alpine ecosystems.The sequence of soil aggregate destruction in the land use types of plantation(13.1%)<shrubland(32.7%)<grassland(47.9%)<farmland(61.8%)shows that plantations strengthen the soil structure.Plantation land had a greater contribution of light fraction organic carbon(28.3%)but a lower contribution of mineral-associated organic carbon(40.6%)to the carbon stock compared to farmland(13.5 and 70.3%).Interestingly,plantation land enhanced the aggregational differentiation of organic carbon and ^(13)C in each density fraction,whereas no such phenomenon existed in the soil organic carbon.Carbon isotope analyses revealed that carbon transfer in the plantation land occurred from the light fraction in macroaggregates(–24.9‰)to the mineral-associated fraction in microaggregates(–19.9‰).When compared to the other three land use types,the low transferability of carbon in aggregates and density fractions in plantation land provides a stable carbon pool for the Tibetan Plateau.This study shows that plantations can mitigate global climate change by slowing carbon transfer and increasing carbon storage at the microscale of aggregates and density fractions in alpine regions.展开更多
To evaluate the validity of different indices in estimating soil readily mineralizable N, soil microbial biomass （Nmic）, soil active N （SAN）, soluble organic N （SON）, net N mineralization rate （NNR） and gross ...To evaluate the validity of different indices in estimating soil readily mineralizable N, soil microbial biomass （Nmic）, soil active N （SAN）, soluble organic N （SON）, net N mineralization rate （NNR） and gross N mineralization rate （GNR） in mineral soils （0-10 cm） from six forest stands located in central Germany were determined and compared with two sampling times： April and November. Additionally, soil density fractionation was conducted for incubated soils （with addition of ^15NH4-N and glucose, 40 days） to observe the sink of added ^15N in different soil fractions. The study showed that Nmic and NNR in most stands differed significantly （P 〈 0.05） between the two sampling times, but not GNR, SAN and SON. In November, no close relationships were found between GNR and other N indices, or between Nrnic, SON, and SAN and forest type. However, in April, GNR was significantly correlated （P 〈 0.05） with Nmic, SAN, and NNR along with Nmlc under beech being significantly higher （P 〈 0.05） than under conifers. Furthermore, density fractionation revealed that the light fraction （LF, 0.063-2 mm, 〉 1.7 gcm^-3） was not correlated with the other N indices. In contrast, results from the incubation study proved that more 15N was incorporated into the heavy fraction （HF 〈 0.063 ram, 〉 1.7 g cm^-3） than into LF, indicaing that more labile N existed in HF than in LF. These findings suggested that attention should be paid to the differences existing in N status between agricultural and forest soils.展开更多
BACKGROUND Hepatic steatosis is a very common problem worldwide.AIM To assess the performance of two-and six-point Dixon magnetic resonance(MR)techniques in the detection,quantification and grading of hepatic steatosi...BACKGROUND Hepatic steatosis is a very common problem worldwide.AIM To assess the performance of two-and six-point Dixon magnetic resonance(MR)techniques in the detection,quantification and grading of hepatic steatosis.METHODS A single-center retrospective study was performed in 62 patients with suspected parenchymal liver disease.MR sequences included two-point Dixon,six-point Dixon,MR spectroscopy(MRS)and MR elastography.Fat fraction(FF)estimates on the Dixon techniques were compared to the MRS-proton density FF(PDFF).Statistical tests used included Pearson’s correlation and receiver operating characteristic.RESULTS FF estimates on the Dixon techniques showed excellent correlation(≥0.95)with MRS-PDFF,and excellent accuracy[area under the receiver operating characteristic(AUROC)≥0.95]in:(1)Detecting steatosis;and(2)Grading severe steatosis,(P<0.001).In iron overload,two-point Dixon was not evaluable due to confounding T2*effects.FF estimates on six-point Dixon vs MRS-PDFF showed a moderate correlation(0.82)in iron overload vs an excellent correlation(0.97)without iron overload,(P<0.03).The accuracy of six-point Dixon in grading mild steatosis improved(AUROC:0.59 to 0.99)when iron overload cases were excluded.The excellent correlation(>0.9)between the Dixon techniques vs MRSPDFF did not change in the presence of liver fibrosis(P<0.01).CONCLUSION Dixon techniques performed satisfactorily for the evaluation of hepatic steatosis but with exceptions.展开更多
Hydrochar(HC)produced by the hydrothermal carbonization(HTC)of typically wet biomass is generally considered to be less effective for carbon(C)sequestration in soils compared to biochar(BC)by pyrolysis,due to a higher...Hydrochar(HC)produced by the hydrothermal carbonization(HTC)of typically wet biomass is generally considered to be less effective for carbon(C)sequestration in soils compared to biochar(BC)by pyrolysis,due to a higher content of more easily decomposable C.Although the recalcitrance of HC is suggested to improve with increasing HTC production temperature,the way it interacts and becomes associated with soil organic matter(SOM)fractions of different stabilities against decomposition,may also influence its effectiveness for C sequestration in soils.In that respect,this study aimed to verify the potential of HCs from maize silage produced at different HTC temperatures(190,210 and 230℃)for C sequestration in a HC-amended sandy loam Podzol.To do this,we conducted a pot trial experiment and traced the fate of HC-derived C(HC-C)within different SOM fractions,namely the free-and occluded particulate organic matter(POMF and POMO,respectively)fractions and that comprising organic matter(OM)bound to clays(OMCl).Approx.1 year after applying 5%of the different HTC temperature HCs to the soil,the SOM fractions were isolated by density fractionation for each HC treatment(HC190,HC210 and HC230)and the control(absent of HC).All fractions and the HCs were analyzed for organic C(OC)content and isotopic signatures(δ^(13)C).From the δ^(13)C signatures,the amount of HC-C and native soil organic carbon(SOC)within each fraction was calculated.Increased C contents and decreased H/C and O/C ratios were observed with increasing HTC production temperatures,which sug-gests a lower stability for the low temperature HC.After ca.1 year,a loss of~20-23%of the bulk soil TOC was found in the HC-amended soils.The POMF fraction of the HC-amended soils showed losses of 68-81%HC-C and 52-72%native SOC,which may be due to a positive priming effect caused by HC addition.The POM_(O) and OM_(Cl) fractions of the HC-amended soils contained more OC than the control,indicating the integration of HC-C together with SOM within these more stable fractions,while the effect of HTC production temperature on the level of decomposition of the resultant HCs was negligible.In all HC treatments,the OM_(Cl) fraction comprised the least amount of HC-C,thus showing the weakest response to C amendment.In conclusion,long(er)-term research on the C net balance that accounts for the observed priming-induced TOC losses and the HC-C enrichment in more stable fractions is required to verify the potential of the different HCs for the purpose of C sequestration in soils.展开更多
Metabolic dysfunction-associated steatotic liver disease(MASLD),previously known as non-alcoholic fatty liver disease(NAFLD),has emerged as a leading cause of chronic liver disease globally,reflecting the convergence ...Metabolic dysfunction-associated steatotic liver disease(MASLD),previously known as non-alcoholic fatty liver disease(NAFLD),has emerged as a leading cause of chronic liver disease globally,reflecting the convergence of rising obesity,insulin resistance,and type 2 diabetes mellitus(1).The disease burden is not only liver-related but systemic,contributing to increased cardiovascular risk,malignancy,and reduced quality of life(2).The clinical spectrum of MASLD ranges from simple steatosis to metabolic dysfunction-associated steatohepatitis(MASH),fibrosis,and cirrhosis,with a growing share of hepatocellular carcinoma cases now being attributed to MASLD rather than viral etiologies(3).MASLD pathophysiology involves a complex interplay of chronic low-grade inflammation,immune cell activation,and systemic metabolic dysfunction,implicating organs beyond the liver,including adipose tissue and spleen(2,3).展开更多
The prevalence of cirrhosis and hepatocellular carcinoma resulting from metabolic dysfunction-associated steatotic liver disease(MASLD)is increasing,posing a significant burden on both the economy and public health(1,...The prevalence of cirrhosis and hepatocellular carcinoma resulting from metabolic dysfunction-associated steatotic liver disease(MASLD)is increasing,posing a significant burden on both the economy and public health(1,2).Although the need for effective therapeutic strategies for MASLD is growing,pharmacologic options remain limited,with resmetirom currently the only approved drug.Consequently,lifestyle modification-particularly weight reduction through diet and exercise-remains the cornerstone of MASLD management.展开更多
Background Type II diabetes mellitus usually related to visceral and other organ （ectopic） fat. The purpose of this study was to detect hepatic and pancreatic fat infiltration in type II diabetes meUitus patients us...Background Type II diabetes mellitus usually related to visceral and other organ （ectopic） fat. The purpose of this study was to detect hepatic and pancreatic fat infiltration in type II diabetes meUitus patients using 3.0T magnetic resonance （MR） and to compare the performance of iterative decomposition of water and fat with echo asymmetry and least-squares estimation （IDEAL-Quant） with single-voxel proton spectroscopy （HI-MRS）. Methods The study protocol was approved by our Institutional Review Board. Written informed consent was obtained from each subject in this study. We prospectively performed IDEAL-Quant and single-voxel proton spectroscopy with an echo time of 35 ms on 24 type II diabetes patients and 10 healthy volunteers. The hepatic proton density fat fraction （HPDFF） and pancreatic proton density fat fraction （PPDFF） were calculated, compared, and analyzed by t-tests and Spearman＇s correlation. Results The HPDFF and PPDFF measured with IDEAL-Quant were significantly different between the healthy volunteers and type II diabetes patients （th=9.377, P=0.000; tp=2.813, P=0.008）. The HPDFF and PPDFF measured with MRS were also significantly different between the healthy volunteers and type II diabetes patients （th=5.342, P=0.000; tp=2.63, P=0.013）. The HPDFF and PPDFF measured by the two methods were in good agreement （rh=0.854, P=-0.000; rp=0.774, P=0.000）. The HPDFF and PPDFF were not significantly correlated with each other （rMRs=0.203, p=0.248; rpDEAL_Quant=0.301, P=0.084）. The PPDFF measured with IDEAL-Quant was associated with body mass index （t=0.377, P=0.028）. Conclusion IDEAL-Quant is a nice method for hepatic and pancreatic fat detection, and it can be applied in clinical practice.展开更多
Quantification of hepatic fat and iron content is important for early detection and monitoring of nonalcoholic fatty liver disease(NAFLD) patients. This study evaluated quantification efficiency of hepatic proton dens...Quantification of hepatic fat and iron content is important for early detection and monitoring of nonalcoholic fatty liver disease(NAFLD) patients. This study evaluated quantification efficiency of hepatic proton density fat fraction(PDFF) by MRI using NAFLD rabbits. R2* was also measured to investigate whether it correlates with fat levels in NAFLD. NAFLD rabbit model was successfully established by high fat and cholesterol diet. Rabbits underwent MRI examination for fat and iron analyses,compared with liver histological findings. MR examinations were performed on a 3.0 T MR system using multi-echo 3 D gradient recalled echo(GRE) sequence. MRI-PDFF showed significant differences between different steatosis grades with medians of3.72%(normal), 5.43%(mild), 9.11%(moderate) and 11.17%(severe), whereas this was not observed in R2*. Close correlation between MRI-PDFF and histological steatosis was observed(r=0.78, P=0.000). Hepatic iron deposit was not found in any rabbits. There was no correlation between R2* and either liver MRI-PDFF or histological steatosis. MR measuring MRI-PDFF and R2* simultaneously provides promising quantification of steatosis and iron. Rabbit NAFLD model confirmed accuracy of MRI-PDFF for liver fat quantification. R2* measurement and relationship between fat and iron of NAFLD liver need further experimental investigation.展开更多
Background and Aims:The redefinition of metabolic-as-sociated fatty liver disease(MAFLD)from nonalcoholic fat-ty liver disease(NAFLD)has caused a revolution in clinical practice,and the characteristics of patients wit...Background and Aims:The redefinition of metabolic-as-sociated fatty liver disease(MAFLD)from nonalcoholic fat-ty liver disease(NAFLD)has caused a revolution in clinical practice,and the characteristics of patients with steatosis but not MAFLD remain unclear.The aims were to compare the diagnosis rate of MAFLD in NAFLD using different steato-sis methods and explore the features of non-MAFLD-NAFLD and MAFLD-non-NAFLD.Methods:A cross-sectional study enrolling consecutive individuals was conducted at three medical centers in southern China from January 2015 to September 2020.Steatosis was evaluated by liver biopsy or magnetic resonance imaging-based proton density fat frac-tion(MRI-PDFF),ultrasound,controlled attenuation param-eter(CAP),and fatty liver index(FLI).Fibrosis was assessed by the NAFLD fibrosis score,transient elastography,or shear wave elastography.Results:The study enrolled 14,985 Chi-nese adults.The agreement of MAFLD and NAFLD diagnoses were 83%for FLI,95%for ultrasound,94%for both CAP and MRI-PDFF,and 95%for liver biopsy.The body mass index,blood pressure and lipid levels among non-MAFLD-NAFLD pa-tients were similar metabolic parameters(p>0.05 for all),but not the alanine aminotransferase and the proportion of pa-tients with insulin resistance,which were significantly higher in non-MAFLD-NAFLD with significant fibrosis.Conclusions:The new MAFLD definition ruled out 5-17%of NAFLD cases.NAFLD and MAFLD-NAFLD involved more severe metabolic abnormalities than MAFLD and MAFLD-non-NAFLD.Non-MAFLD-NAFLD patients with significant fibrosis had more se-vere liver injury and increased glycemic dysregulation within the normal range.Attention should be paid to its progression.展开更多
Genetic susceptibility to metabolic associated fatty liver disease(MAFLD)is complex and poorly characterized.Accurate characterization of the genetic background of hepatic fat content would provide insights into disea...Genetic susceptibility to metabolic associated fatty liver disease(MAFLD)is complex and poorly characterized.Accurate characterization of the genetic background of hepatic fat content would provide insights into disease etiology and causality of risk factors.We performed genome-wide association study(GWAS)on two noninvasive definitions of hepatic fat content:magnetic resonance imaging proton density fat fraction(MRI-PDFF)in 16,050 participants and fatty liver index(FLI)in 388,701 participants from the United Kingdom(UK)Biobank(UKBB).Heritability,genetic overlap,and similarity between hepatic fat content phenotypes were analyzed,and replicated in 10,398 participants from the University Medical Center Groningen(UMCG)Genetics Lifelines Initiative(UGLI).Meta-analysis of GWASs of MRI-PDFF in UKBB revealed five statistically significant loci,including two novel genomic loci harboring CREB3L1(rs72910057-T,P=5.40E−09)and GCM1(rs1491489378-T,P=3.16E−09),respectively,as well as three previously reported loci:PNPLA3,TM6SF2,and APOE.GWAS of FLI in UKBB identified 196 genome-wide significant loci,of which 49 were replicated in UGLI,with top signals in ZPR1(P=3.35E−13)and FTO(P=2.11E−09).Statistically significant genetic correlation(rg)between MRI-PDFF(UKBB)and FLI(UGLI)GWAS results was found(rg=0.5276,P=1.45E−03).Novel MRI-PDFF genetic signals(CREB3L1 and GCM1)were replicated in the FLI GWAS.We identified two novel genes for MRI-PDFF and 49 replicable loci for FLI.Despite a difference in hepatic fat content assessment between MRI-PDFF and FLI,a substantial similar genetic architecture was found.FLI is identified as an easy and reliable approach to study hepatic fat content at the population level.展开更多
Metabolic dysfunction associated steatohepatitis(MASH)is a silent epidemic,hiding in the shadows of obesity,and often silently advancing towards the grave complication of cirrhosis.The distinction between MASH and sim...Metabolic dysfunction associated steatohepatitis(MASH)is a silent epidemic,hiding in the shadows of obesity,and often silently advancing towards the grave complication of cirrhosis.The distinction between MASH and simple hepatic steatosis,which is under the spectrum of metabolic dysfunction-associated steatotic liver disease(MASLD),is highly desired as it provides critical information about the prognosis of the patient.Noninvasive indicators,such as fibrosis-4(FIB-4)index and nonalcoholic fatty liver disease(NAFLD)fibrosis score that includes conventional laboratory data and clinical parameters.展开更多
Background:High liver fat content(LFC)induces increased risks of both hepatic and extrahepatic progression in metabolic dysfunction-associated steatotic liver disease(MASLD),while maintaining a significant decline in ...Background:High liver fat content(LFC)induces increased risks of both hepatic and extrahepatic progression in metabolic dysfunction-associated steatotic liver disease(MASLD),while maintaining a significant decline in magnetic resonance imaging-based proton density fat fraction(MRI-PDFF)(≥30%decline relative to baseline)without worsening fibrosis results in improved histological severity and prognosis.However,the factors associated with the loss of sustained responses to treatment remain unclear,and we aim to identify them.Methods:Consecutive treatment-naïve MASLD patients between January 2015 and February 2022,with follow-up until April 2023,were included in this prospective cohort study.LFC quantified by MRI-PDFF and liver stiffness measurements(LSM)determined by two-dimensional shear wave elastography(2D-SWE)were evaluated at weeks 0,24 and 48.MRI-PDFF response was defined as a≥30%relative decline in PDFF values,and LSM response was defined as a≥1 stage decline from baseline.Results:A total of 602 MASLD patients were enrolled.Of the 303 patients with a 24-week MRI-PDFF response and complete follow-up of 48 weeks,the rate of loss of MRI-PDFF response was 29.4%,and multivariable logistic regression analyses showed that 24-week insulin resistance(IR),still regular exercise and caloric restriction after 24 weeks,and the relative decline in LFC were risk factors for loss of MRI-PDFF response.Loss of LSM response at 48 weeks occurred in 15.9%of patients,and multivariable analysis confirmed 24-week serum total bile acid(TBA)levels and the relative decline in TBA from baseline as independent predictors.No significant association was found at 48 weeks between loss of MRI-PDFF response and loss of LSM response.Conclusions:MASLD patients with IR and high TBA levels are at higher risks of subsequent diminished sustained improvements of steatosis and fibrosis,respectively.展开更多
基金Supported by the Leap-forward Development Program for Beijing Biopharmaceutical Industry(G20),No.Z171100001717008the Fundamental Research Funds for the Central Universities and Research projects on biomedical transformation of China-Japan Friendship Hospital,No.PYBZ1815.
文摘BACKGROUND Nonalcoholic fatty liver disease(NAFLD)is the most common chronic liver disea-se.The accuracy of noninvasive biomarkers for detecting hepatic steatosis is still limited.AIM To assess the diagnostic performance of noninvasive steatosis biomarkers in diag-nosing NAFLD using magnetic resonance imaging proton density fat fraction(MRI-PDFF)as the gold standard.METHODS A total of 131 suspected NAFLD patients(60%male,median age 36 years)under-going MRI-PDFF were consecutively recruited from a tertiary hospital.Steatosis grades determined by MRI-PDFF were classified as none(<5%),mild(5%-11%),moderate(11%-17%),and severe(≥17%).Six steatosis biomarkers were calculated according to clinical parameters and laboratory tests,including fatty liver index,hepatic steatosis index,ZJU index,Framingham steatosis index,triglycerides and glucose index,and visceral adiposity index.The accuracy of these biomarkers in detecting hepatic steatosis was evaluated using the area under the receiver operating characteristic curves(AUCs).The Youden index was used to determine the optimal cut-off for each biomarker.The linear trend analysis of each biomarker across the steatosis grades was conducted by Mantel-Haenszelχ2 test.Spearman's rank correlation assessed the relationship between steatosis biomarkers and MRI-PDFF.RESULTS Steatosis grades based on MRI-PDFF prevalence were:None 27%,mild 40%,moderate 15%and severe 18%.Six steatosis biomarkers showed a linear trend across the steatosis grades and a significant positive correlation with MRI-PDFF.The six steatosis biomarkers demonstrated AUCs near 0.90(range:0.857-0.912,all P<0.001)for diagnosing NAFLD by MRI-PDFF≥5%.The optimal cut-offs showed sensitivity between 84.4%-91.7%and specificity between 71.4%-85.7%.The diagnostic performance of these biomarkers in detecting moderate-to-severe and severe steatosis was relatively weaker.CONCLUSION These noninvasive steatosis biomarkers accurately diagnosed NAFLD and correlated well with MRI-PDFF for detecting NAFLD,but they did not effectively detect moderate or severe steatosis.
基金financial support from the Natural Science Foundation of China and BaoSteel Group Co.,Ltd.(Grant No.U1460203)the International Science&Technology Cooperation Program of China(Grant No.2015DFG51950)the Fundamental Research Funds for the Central Universities
文摘A new model on predicting the density of hot-rolled multi-phased medium-Mn steel has been presen ted on the basis of thermodynamic calculations. This is an integrated model, which includes one for calculating the retained austenite （RA） fraction and the other for volume expansion during the aus tenite-to martensite transformation, because both of them are key parameters for calculating the den- sity of steel at ambient temperature. The existing empirical equations for calculating Mx temperature and lattice constants of both martensite and austenite have been all rcassessed by the XRD measure ments on the microstructures of seven hot-rolled medium-Mn steels. Finally, the densities ot seven steels were calculated merely from compositions and compared with the measured ones. The differ ence between them is no more than 1 %, suggesting that the presented model should be of good value in designing the low density steels.
基金supported by the Equipment Development Department ‘‘13th Five-year” Equipment Research Field Foundation of China Central Military Commission(No.6140244010216HT15001)
文摘Estimating the Probability Density Function（PDF） of the performance function is a direct way for structural reliability analysis,and the failure probability can be easily obtained by integration in the failure domain.However,efficiently estimating the PDF is still an urgent problem to be solved.The existing fractional moment based maximum entropy has provided a very advanced method for the PDF estimation,whereas the main shortcoming is that it limits the application of the reliability analysis method only to structures with independent inputs.While in fact,structures with correlated inputs always exist in engineering,thus this paper improves the maximum entropy method,and applies the Unscented Transformation（UT） technique to compute the fractional moments of the performance function for structures with correlations,which is a very efficient moment estimation method for models with any inputs.The proposed method can precisely estimate the probability distributions of performance functions for structures with correlations.Besides,the number of function evaluations of the proposed method in reliability analysis,which is determined by UT,is really small.Several examples are employed to illustrate the accuracy and advantages of the proposed method.
文摘Purpose: Bone marrow and muscle adiposity have been considered to correlate with osteoporosis and Sarcopenia. Proton Density Fat Fraction (PDFF) can be measured by Magnetic Resonance Imaging (MRI). The purpose of the present study was to measure PDFF in the lumbar spine, paraspinal muscle and subcutaneous fat tissue. Methods: Participants were comprised of 30 patients (18 males, 12 females;age range, 14 - 87 years) who underwent MRI due to low back symptoms. PDFFs for the body of the fourth lumbar vertebra (L4), paraspinal muscle, and subcutaneous fat were measured. Results: PDFFs of the vertebral body and subcutaneous fat were significantly higher than that of paraspinal muscle (p < 0.001). PDFF was significantly higher for subcutaneous fat than for the vertebral body (p < 0.001). Although no significant differences in PDFF of the vertebral body, paraspinal muscle, and subcutaneous fat between females and males, PDFFs of the vertebral body and paraspinal muscle were significantly higher in older subjects (>63 years) than in younger subjects (Conclusions: PDFF of the vertebral body was significantly higher than that of paraspinal muscle. PDFFs of the vertebral body and paraspinal muscle were significantly lower in younger subjects than in older subjects.
基金the Chinese Academy of Sciences for their financial support and research facilitiesfunded by the National Key Research and Development Program of China(2022YFD1500100)+1 种基金the Strategic Priority Research Program of the Chinese Academy of Sciences(XDA28070100)the China Agriculture Research System of MOF and MARA(CARS04)。
文摘The accumulation of soil organic carbon(SOC)and total nitrogen(TN)is easily accomplished by returning crop straw,which strongly affects the formation and pore structure of aggregates,especially in black soil.We returned maize straw at different rates(6,000,9,000,12,000 and 15,000 kg ha^(-1))for nine years to investigate its influence on the SOC and TN contents in the SOC fractions of aggregates by combining size and density fractionation.Their subsequent influences on pore morphology and size distribution characteristics were examined using X-ray microcomputed tomography scanning(μCT).The results showed that returning straw significantly increased the contents of C and N in the SOC fractions of aggregates,especially at the return rates of 12,000 and 15,000 kg ha^(-1),which in turn promoted aggregate formation and stability,and ultimately amended pore structure.The pore size>100μm,porosity(>2μm),and morphological characteristics(anisotropy,circularity,connectivity and fractal dimension)significantly increased,but the total number of pores significantly decreased(P<0.05).Our results indicated that the amendment of the pore morphology and size distribution of soil aggregates was primarily controlled by the higher contents of C and N in the density fractions of aggregates,rather than in the aggregate sizes.Furthermore,this pore network reconfiguration favored the storage of C and N simultaneously.The findings of this study offer valuable new insights into the relationships between C and N storage and the pore characteristics in soil aggregates under straw return.
基金supported by the National Natural Sci-ence Foundation of China (No. 30470303)the Key Project of the Knowledge Innovation Program of the Chinese Academy of Sciences (No. KZCX2-YW-405)
文摘The importance of soil organic carbon （SOC） under forests in the global carbon cycle depends on the stability of the soil carbon and its availability to soil microbial biomass. We investigated the effects of successive rotations of Chinese fir （Cunninghamia lanceolata （Lamb.） Hook） plantations on the stability of SOC and its availability to microbes by adopting the two-step hydrolysis with H2SO4 and density fractionation. The results showed that successive rotations of Chinese fir decreased the quantity of total SOC, recalcitrant fraction, and carbohydrates in Labile Pool I （LPI）, and microbial properties evidently, especially at 0-10 cm horizon. However, cellulose included in Labile Pool Ⅱ （LP Ⅱ） and the cellulose/total carbohydrates ratio increased in successive rotations of Chinese fir. The noncellulose of carbohydrates included in LPI maybe highly available to soil microbial biomass. Hence the availability of SOC to microbial biomass declined over the successive rotations. Although there was no significant change in recalcitrance of SOC over the successive rotations of Chinese fir, the percentage of heavy fraction to total SOC increased, suggesting that the degree of physical protection for SOC increased and SOC became more stable over the successive rotations. The degradation of SOC quality in successive rotation soils may be attributed to worse environmental conditions resulted from disturbance that related to ＂slash and burn＂ site preparation. Being highly correlated with soil microbial properties, the cellulose/total carbohydrates ratio as an effective indicator of changes in availability of SOC to microbial biomass brought by management practices in forest soils.
基金supported by the USDA National Institute of Food and Agriculture(NIFA),Evans Allen Grant,USA(No.224120)the National Science Foundation(NSF-CREST-CFEA),USA(No.1036600)the Agricultural Experimental Station,Alabama A&M University,Alabama,USA(Journal#:660)
文摘Forest management practices such as prescribed burning and thinning in forest ecosystems may alter the properties of soil organic matter （SOM）. In this study, surface softs from field plots in the Bankhead National Forest, Alabama, USA, were used to investigate possible SOM transformations induced by thinning and burning. Elemental analysis and solid-state 13C cross polarization magic angle spinning nuclear magnetic resonance （13C CPMAS NMR） spectroscopy were used to characterize SOM fractions in whole soils, humic substances, and density fractions. Our data revealed that the changes in SOM fractions due to the repeated burning carried out in the forest ecosystem studied were involved mainly with alkyl C, O-alkyl C, and carbohydrate functional groups, implying that most prominent reactions that occurred involved dehydrogenation, de-oxygenation, and decarboxylation. In addition, burning and thinning might have also affected the distribution and composition of free and occluded particulate SOM fractions. The limited structural changes in SOM fractions suggested that low-intensity prescribed fire in the forest ecosystem studied will not create major structural changes in SOM fractions.
基金financially supported by the National Natural Science Foundation of China (42477044,32171648 and U23A2017)the Hubei Provincial Science and Technology Program,China (2025AFD451 and 2022CFB030)。
文摘Insight into the carbon turnover in soil aggregates and density fractions is essential for reducing the uncertainty in estimating carbon pools on the Tibetan Plateau,and how they vary with land use type is unclear.In this study,the effect of land use type on carbon storage and fractionation was quantified based on organic carbon and its ^(13)C abundance at the microscale of soil aggregates and density fractions in Tibetan alpine ecosystems.The sequence of soil aggregate destruction in the land use types of plantation(13.1%)<shrubland(32.7%)<grassland(47.9%)<farmland(61.8%)shows that plantations strengthen the soil structure.Plantation land had a greater contribution of light fraction organic carbon(28.3%)but a lower contribution of mineral-associated organic carbon(40.6%)to the carbon stock compared to farmland(13.5 and 70.3%).Interestingly,plantation land enhanced the aggregational differentiation of organic carbon and ^(13)C in each density fraction,whereas no such phenomenon existed in the soil organic carbon.Carbon isotope analyses revealed that carbon transfer in the plantation land occurred from the light fraction in macroaggregates(–24.9‰)to the mineral-associated fraction in microaggregates(–19.9‰).When compared to the other three land use types,the low transferability of carbon in aggregates and density fractions in plantation land provides a stable carbon pool for the Tibetan Plateau.This study shows that plantations can mitigate global climate change by slowing carbon transfer and increasing carbon storage at the microscale of aggregates and density fractions in alpine regions.
基金Project supported by the German Research Council, Germany (No. DFG Graduiertenkolleg 339).
文摘To evaluate the validity of different indices in estimating soil readily mineralizable N, soil microbial biomass （Nmic）, soil active N （SAN）, soluble organic N （SON）, net N mineralization rate （NNR） and gross N mineralization rate （GNR） in mineral soils （0-10 cm） from six forest stands located in central Germany were determined and compared with two sampling times： April and November. Additionally, soil density fractionation was conducted for incubated soils （with addition of ^15NH4-N and glucose, 40 days） to observe the sink of added ^15N in different soil fractions. The study showed that Nmic and NNR in most stands differed significantly （P 〈 0.05） between the two sampling times, but not GNR, SAN and SON. In November, no close relationships were found between GNR and other N indices, or between Nrnic, SON, and SAN and forest type. However, in April, GNR was significantly correlated （P 〈 0.05） with Nmic, SAN, and NNR along with Nmlc under beech being significantly higher （P 〈 0.05） than under conifers. Furthermore, density fractionation revealed that the light fraction （LF, 0.063-2 mm, 〉 1.7 gcm^-3） was not correlated with the other N indices. In contrast, results from the incubation study proved that more 15N was incorporated into the heavy fraction （HF 〈 0.063 ram, 〉 1.7 g cm^-3） than into LF, indicaing that more labile N existed in HF than in LF. These findings suggested that attention should be paid to the differences existing in N status between agricultural and forest soils.
文摘BACKGROUND Hepatic steatosis is a very common problem worldwide.AIM To assess the performance of two-and six-point Dixon magnetic resonance(MR)techniques in the detection,quantification and grading of hepatic steatosis.METHODS A single-center retrospective study was performed in 62 patients with suspected parenchymal liver disease.MR sequences included two-point Dixon,six-point Dixon,MR spectroscopy(MRS)and MR elastography.Fat fraction(FF)estimates on the Dixon techniques were compared to the MRS-proton density FF(PDFF).Statistical tests used included Pearson’s correlation and receiver operating characteristic.RESULTS FF estimates on the Dixon techniques showed excellent correlation(≥0.95)with MRS-PDFF,and excellent accuracy[area under the receiver operating characteristic(AUROC)≥0.95]in:(1)Detecting steatosis;and(2)Grading severe steatosis,(P<0.001).In iron overload,two-point Dixon was not evaluable due to confounding T2*effects.FF estimates on six-point Dixon vs MRS-PDFF showed a moderate correlation(0.82)in iron overload vs an excellent correlation(0.97)without iron overload,(P<0.03).The accuracy of six-point Dixon in grading mild steatosis improved(AUROC:0.59 to 0.99)when iron overload cases were excluded.The excellent correlation(>0.9)between the Dixon techniques vs MRSPDFF did not change in the presence of liver fibrosis(P<0.01).CONCLUSION Dixon techniques performed satisfactorily for the evaluation of hepatic steatosis but with exceptions.
文摘Hydrochar(HC)produced by the hydrothermal carbonization(HTC)of typically wet biomass is generally considered to be less effective for carbon(C)sequestration in soils compared to biochar(BC)by pyrolysis,due to a higher content of more easily decomposable C.Although the recalcitrance of HC is suggested to improve with increasing HTC production temperature,the way it interacts and becomes associated with soil organic matter(SOM)fractions of different stabilities against decomposition,may also influence its effectiveness for C sequestration in soils.In that respect,this study aimed to verify the potential of HCs from maize silage produced at different HTC temperatures(190,210 and 230℃)for C sequestration in a HC-amended sandy loam Podzol.To do this,we conducted a pot trial experiment and traced the fate of HC-derived C(HC-C)within different SOM fractions,namely the free-and occluded particulate organic matter(POMF and POMO,respectively)fractions and that comprising organic matter(OM)bound to clays(OMCl).Approx.1 year after applying 5%of the different HTC temperature HCs to the soil,the SOM fractions were isolated by density fractionation for each HC treatment(HC190,HC210 and HC230)and the control(absent of HC).All fractions and the HCs were analyzed for organic C(OC)content and isotopic signatures(δ^(13)C).From the δ^(13)C signatures,the amount of HC-C and native soil organic carbon(SOC)within each fraction was calculated.Increased C contents and decreased H/C and O/C ratios were observed with increasing HTC production temperatures,which sug-gests a lower stability for the low temperature HC.After ca.1 year,a loss of~20-23%of the bulk soil TOC was found in the HC-amended soils.The POMF fraction of the HC-amended soils showed losses of 68-81%HC-C and 52-72%native SOC,which may be due to a positive priming effect caused by HC addition.The POM_(O) and OM_(Cl) fractions of the HC-amended soils contained more OC than the control,indicating the integration of HC-C together with SOM within these more stable fractions,while the effect of HTC production temperature on the level of decomposition of the resultant HCs was negligible.In all HC treatments,the OM_(Cl) fraction comprised the least amount of HC-C,thus showing the weakest response to C amendment.In conclusion,long(er)-term research on the C net balance that accounts for the observed priming-induced TOC losses and the HC-C enrichment in more stable fractions is required to verify the potential of the different HCs for the purpose of C sequestration in soils.
文摘Metabolic dysfunction-associated steatotic liver disease(MASLD),previously known as non-alcoholic fatty liver disease(NAFLD),has emerged as a leading cause of chronic liver disease globally,reflecting the convergence of rising obesity,insulin resistance,and type 2 diabetes mellitus(1).The disease burden is not only liver-related but systemic,contributing to increased cardiovascular risk,malignancy,and reduced quality of life(2).The clinical spectrum of MASLD ranges from simple steatosis to metabolic dysfunction-associated steatohepatitis(MASH),fibrosis,and cirrhosis,with a growing share of hepatocellular carcinoma cases now being attributed to MASLD rather than viral etiologies(3).MASLD pathophysiology involves a complex interplay of chronic low-grade inflammation,immune cell activation,and systemic metabolic dysfunction,implicating organs beyond the liver,including adipose tissue and spleen(2,3).
基金supported by Japan Agency for Medical Research and Development(JP25fk0210123 to M.K.)Japanese Ministry of Health,Labour and Welfare(23HC2001 to M.K.)+1 种基金from Japan Agency for Medical Research and Development(JP25fk0310535,JP25fk0210174,and JP25fk0210123 to N.T.)Japanese Ministry of Health,Labour and Welfare(23HC2003 and 23HC2002 to N.T.).
文摘The prevalence of cirrhosis and hepatocellular carcinoma resulting from metabolic dysfunction-associated steatotic liver disease(MASLD)is increasing,posing a significant burden on both the economy and public health(1,2).Although the need for effective therapeutic strategies for MASLD is growing,pharmacologic options remain limited,with resmetirom currently the only approved drug.Consequently,lifestyle modification-particularly weight reduction through diet and exercise-remains the cornerstone of MASLD management.
文摘Background Type II diabetes mellitus usually related to visceral and other organ （ectopic） fat. The purpose of this study was to detect hepatic and pancreatic fat infiltration in type II diabetes meUitus patients using 3.0T magnetic resonance （MR） and to compare the performance of iterative decomposition of water and fat with echo asymmetry and least-squares estimation （IDEAL-Quant） with single-voxel proton spectroscopy （HI-MRS）. Methods The study protocol was approved by our Institutional Review Board. Written informed consent was obtained from each subject in this study. We prospectively performed IDEAL-Quant and single-voxel proton spectroscopy with an echo time of 35 ms on 24 type II diabetes patients and 10 healthy volunteers. The hepatic proton density fat fraction （HPDFF） and pancreatic proton density fat fraction （PPDFF） were calculated, compared, and analyzed by t-tests and Spearman＇s correlation. Results The HPDFF and PPDFF measured with IDEAL-Quant were significantly different between the healthy volunteers and type II diabetes patients （th=9.377, P=0.000; tp=2.813, P=0.008）. The HPDFF and PPDFF measured with MRS were also significantly different between the healthy volunteers and type II diabetes patients （th=5.342, P=0.000; tp=2.63, P=0.013）. The HPDFF and PPDFF measured by the two methods were in good agreement （rh=0.854, P=-0.000; rp=0.774, P=0.000）. The HPDFF and PPDFF were not significantly correlated with each other （rMRs=0.203, p=0.248; rpDEAL_Quant=0.301, P=0.084）. The PPDFF measured with IDEAL-Quant was associated with body mass index （t=0.377, P=0.028）. Conclusion IDEAL-Quant is a nice method for hepatic and pancreatic fat detection, and it can be applied in clinical practice.
文摘Quantification of hepatic fat and iron content is important for early detection and monitoring of nonalcoholic fatty liver disease(NAFLD) patients. This study evaluated quantification efficiency of hepatic proton density fat fraction(PDFF) by MRI using NAFLD rabbits. R2* was also measured to investigate whether it correlates with fat levels in NAFLD. NAFLD rabbit model was successfully established by high fat and cholesterol diet. Rabbits underwent MRI examination for fat and iron analyses,compared with liver histological findings. MR examinations were performed on a 3.0 T MR system using multi-echo 3 D gradient recalled echo(GRE) sequence. MRI-PDFF showed significant differences between different steatosis grades with medians of3.72%(normal), 5.43%(mild), 9.11%(moderate) and 11.17%(severe), whereas this was not observed in R2*. Close correlation between MRI-PDFF and histological steatosis was observed(r=0.78, P=0.000). Hepatic iron deposit was not found in any rabbits. There was no correlation between R2* and either liver MRI-PDFF or histological steatosis. MR measuring MRI-PDFF and R2* simultaneously provides promising quantification of steatosis and iron. Rabbit NAFLD model confirmed accuracy of MRI-PDFF for liver fat quantification. R2* measurement and relationship between fat and iron of NAFLD liver need further experimental investigation.
基金National Natural Science Foundation of China(81870404,81670518,81170392)Guangdong Science and Technology Department(2014A020212118)+1 种基金Chinese Foundation for Hepatitis Prevention and Control(TQGB20140083)China postdoctoral science foundation(2020M683128).
文摘Background and Aims:The redefinition of metabolic-as-sociated fatty liver disease(MAFLD)from nonalcoholic fat-ty liver disease(NAFLD)has caused a revolution in clinical practice,and the characteristics of patients with steatosis but not MAFLD remain unclear.The aims were to compare the diagnosis rate of MAFLD in NAFLD using different steato-sis methods and explore the features of non-MAFLD-NAFLD and MAFLD-non-NAFLD.Methods:A cross-sectional study enrolling consecutive individuals was conducted at three medical centers in southern China from January 2015 to September 2020.Steatosis was evaluated by liver biopsy or magnetic resonance imaging-based proton density fat frac-tion(MRI-PDFF),ultrasound,controlled attenuation param-eter(CAP),and fatty liver index(FLI).Fibrosis was assessed by the NAFLD fibrosis score,transient elastography,or shear wave elastography.Results:The study enrolled 14,985 Chi-nese adults.The agreement of MAFLD and NAFLD diagnoses were 83%for FLI,95%for ultrasound,94%for both CAP and MRI-PDFF,and 95%for liver biopsy.The body mass index,blood pressure and lipid levels among non-MAFLD-NAFLD pa-tients were similar metabolic parameters(p>0.05 for all),but not the alanine aminotransferase and the proportion of pa-tients with insulin resistance,which were significantly higher in non-MAFLD-NAFLD with significant fibrosis.Conclusions:The new MAFLD definition ruled out 5-17%of NAFLD cases.NAFLD and MAFLD-NAFLD involved more severe metabolic abnormalities than MAFLD and MAFLD-non-NAFLD.Non-MAFLD-NAFLD patients with significant fibrosis had more se-vere liver injury and increased glycemic dysregulation within the normal range.Attention should be paid to its progression.
基金supported by the Netherlands Organization for Scientific Research NWO(Grant No.175.010.2007.006)the Economic Structure Enhancing Fund of the Dutch government+20 种基金the Ministry of Economic Affairsthe Ministry of Education,Culture,and Sciencethe Ministry for Health,Welfare,and Sportsthe Northern Netherlands Alliancethe Province of Groningen,University Medical Center Groningenthe University of Groningen,Dutch Kidney Foundation,and Dutch Diabetes Research Foundationsupported by the Dutch Heart Foundation IN-CONTROL(Grant No.CVON2018-27)the ERC Consolidator Grant(Grant No.101001678)the NWO VICI(Grant No.VI.C.202.022)the Netherlands Organ-on-Chip Initiative,an NWO Gravitation project(Grant No.024.003.001)funded by the Ministry of Education,CultureScience of the government of The Netherlandssupported by the Chinese Scholarship Council.Dasha V.Zhernakova was supported by the NWO VENI(Grant No.194.006)supported by the Seerave Foundation.Rinse K.Weersma and Ranko Gacesa were supported by the TIMID project(Grant No.LSHM18057-SGF)financed by the PPP Allowance made available by Top Sector Life Sciences&Health to Samenwerkende Gezondheidsfondsen(SGF)to stimulate public–private partnerships and co-financing by health foundations that are part of the SGFsupported by the NWO VENI(Grant No.09150161810030)the Health∼Holland Public Private Partnership from the Dutch Ministry of Economic Affairs(Grant No.#PPP-2019-024)supported by the UK Medical Research Council and Wellcome Trustthe UK Department of Healththe Scottish and Welsh Governmentsthe North West Development Agencythe British Heart Foundationthe Diabetes UK.
文摘Genetic susceptibility to metabolic associated fatty liver disease(MAFLD)is complex and poorly characterized.Accurate characterization of the genetic background of hepatic fat content would provide insights into disease etiology and causality of risk factors.We performed genome-wide association study(GWAS)on two noninvasive definitions of hepatic fat content:magnetic resonance imaging proton density fat fraction(MRI-PDFF)in 16,050 participants and fatty liver index(FLI)in 388,701 participants from the United Kingdom(UK)Biobank(UKBB).Heritability,genetic overlap,and similarity between hepatic fat content phenotypes were analyzed,and replicated in 10,398 participants from the University Medical Center Groningen(UMCG)Genetics Lifelines Initiative(UGLI).Meta-analysis of GWASs of MRI-PDFF in UKBB revealed five statistically significant loci,including two novel genomic loci harboring CREB3L1(rs72910057-T,P=5.40E−09)and GCM1(rs1491489378-T,P=3.16E−09),respectively,as well as three previously reported loci:PNPLA3,TM6SF2,and APOE.GWAS of FLI in UKBB identified 196 genome-wide significant loci,of which 49 were replicated in UGLI,with top signals in ZPR1(P=3.35E−13)and FTO(P=2.11E−09).Statistically significant genetic correlation(rg)between MRI-PDFF(UKBB)and FLI(UGLI)GWAS results was found(rg=0.5276,P=1.45E−03).Novel MRI-PDFF genetic signals(CREB3L1 and GCM1)were replicated in the FLI GWAS.We identified two novel genes for MRI-PDFF and 49 replicable loci for FLI.Despite a difference in hepatic fat content assessment between MRI-PDFF and FLI,a substantial similar genetic architecture was found.FLI is identified as an easy and reliable approach to study hepatic fat content at the population level.
文摘Metabolic dysfunction associated steatohepatitis(MASH)is a silent epidemic,hiding in the shadows of obesity,and often silently advancing towards the grave complication of cirrhosis.The distinction between MASH and simple hepatic steatosis,which is under the spectrum of metabolic dysfunction-associated steatotic liver disease(MASLD),is highly desired as it provides critical information about the prognosis of the patient.Noninvasive indicators,such as fibrosis-4(FIB-4)index and nonalcoholic fatty liver disease(NAFLD)fibrosis score that includes conventional laboratory data and clinical parameters.
基金National Natural Science Foundation of China(grant Nos.81870404 and 82100648)Natural Science Foundation of Guangdong Province,China(grant Nos.2021A1515011442 and 2022A1515012369)China Postdoctoral Science Foundation(grant No.2020M683128).
文摘Background:High liver fat content(LFC)induces increased risks of both hepatic and extrahepatic progression in metabolic dysfunction-associated steatotic liver disease(MASLD),while maintaining a significant decline in magnetic resonance imaging-based proton density fat fraction(MRI-PDFF)(≥30%decline relative to baseline)without worsening fibrosis results in improved histological severity and prognosis.However,the factors associated with the loss of sustained responses to treatment remain unclear,and we aim to identify them.Methods:Consecutive treatment-naïve MASLD patients between January 2015 and February 2022,with follow-up until April 2023,were included in this prospective cohort study.LFC quantified by MRI-PDFF and liver stiffness measurements(LSM)determined by two-dimensional shear wave elastography(2D-SWE)were evaluated at weeks 0,24 and 48.MRI-PDFF response was defined as a≥30%relative decline in PDFF values,and LSM response was defined as a≥1 stage decline from baseline.Results:A total of 602 MASLD patients were enrolled.Of the 303 patients with a 24-week MRI-PDFF response and complete follow-up of 48 weeks,the rate of loss of MRI-PDFF response was 29.4%,and multivariable logistic regression analyses showed that 24-week insulin resistance(IR),still regular exercise and caloric restriction after 24 weeks,and the relative decline in LFC were risk factors for loss of MRI-PDFF response.Loss of LSM response at 48 weeks occurred in 15.9%of patients,and multivariable analysis confirmed 24-week serum total bile acid(TBA)levels and the relative decline in TBA from baseline as independent predictors.No significant association was found at 48 weeks between loss of MRI-PDFF response and loss of LSM response.Conclusions:MASLD patients with IR and high TBA levels are at higher risks of subsequent diminished sustained improvements of steatosis and fibrosis,respectively.
