BACKGROUND Several studies have demonstrated a correlation between esophageal cancer(EC)and perturbed urinary metabolomic profiles,but none has described the correlation between urine metabolite profiles and those of ...BACKGROUND Several studies have demonstrated a correlation between esophageal cancer(EC)and perturbed urinary metabolomic profiles,but none has described the correlation between urine metabolite profiles and those of the tumor and adjacent esophageal mucosa in the same patient.AIM To investigate how urinary metabolic phenotypes were linked to the changes in the biochemical landscape of esophageal tumors.METHODS Nuclear magnetic resonance-based metabolomics were applied to esophageal tumor tissues and adjacent normal mucosal tissues alongside patient-matched urine samples.RESULTS Analysis revealed that specific metabolite changes overlapped across both metrics,including glucose,glutamate,citrate,glycine,creatinine and taurine,indicating that the networks for metabolic pathway perturbations in EC,potentially involved in but not limited to disruption of fatty acid metabolism,glucose and glycolytic metabolism,tricarboxylic acid cycle and glutaminolysis.Additionally,changes in most urinary biomarkers correlated with changes in biomarker candidates in EC tissues,implying enhanced energy production for rapid cell proliferation.CONCLUSION Overall,these associations provide evidence for distinct metabolic signatures and pathway disturbances between the tumor tissues and urine of EC patients,and changes in urinary metabolic signature could reflect reprogramming of the aforementioned metabolic pathways in EC tissues.Further investigation is needed to validate these initial findings using larger samples and to establish the underlying mechanism of EC progression.展开更多
Acute kidney injury(AKI)is a significant risk factor for chronic kidney disease(CKD),yet the mechanisms driving this progression remain unclear(Kellum et al.2021).Given the kidney's role in homeostasis,AKI profoun...Acute kidney injury(AKI)is a significant risk factor for chronic kidney disease(CKD),yet the mechanisms driving this progression remain unclear(Kellum et al.2021).Given the kidney's role in homeostasis,AKI profoundly impacts systemic health,often leading to CKD,characterized by persistent damage or reduced glomerular filtration rate(GFR)(Stevens et al.2024).The high incidence of AKI and its strong association with subsequent CKD necessitates a deeper understanding of the transition process.展开更多
AIM To develop metabonomic models(MMs), using 1 H nuclear magnetic resonance(NMR) spectra of serum, to predict significant liver fibrosis(SF: Metavir ≥ F2), advanced liver fibrosis(AF: METAVIR ≥ F3) and cirrhosis(C:...AIM To develop metabonomic models(MMs), using 1 H nuclear magnetic resonance(NMR) spectra of serum, to predict significant liver fibrosis(SF: Metavir ≥ F2), advanced liver fibrosis(AF: METAVIR ≥ F3) and cirrhosis(C: METAVIR = F4 or clinical cirrhosis) in chronic hepatitis C(CHC) patients. Additionally, to compare the accuracy of the MMs with the aspartate aminotransferase to platelet ratio index(APRI) and fibrosis index based on four factors(FIB-4). METHODS Sixty-nine patients who had undergone biopsy in the previous 12 mo or had clinical cirrhosis were included. The presence of any other liver disease was a criterion for exclusion. The MMs, constructed using partial least squares discriminant analysis and linear discriminant analysis formalisms, were tested by cross-validation, considering SF, AF and C. RESULTS Results showed that forty-two patients(61%) presented SF, 28(40%) AF and 18(26%) C. The MMs showed sensitivity and specificity of 97.6% and 92.6% to predict SF; 96.4% and 95.1% to predict AF; and 100% and 98.0% to predict C. Besides that, the MMs correctly classified all 27(39.7%) and 25(38.8%) patients with intermediate values of APRI and FIB-4, respectively. CONCLUSION The metabonomic strategy performed excellently in predicting significant and advanced liver fibrosis in CHC patients, including those in the gray zone of APRI and FIB-4, which may contribute to reducing the need for these patients to undergo liver biopsy.展开更多
Metabolomics is defined as the quantitative measurement of the dynamic multiparametric metabolic response of living systems to pathophysiological stimuli or genetic modification.It is an"omics"technique that...Metabolomics is defined as the quantitative measurement of the dynamic multiparametric metabolic response of living systems to pathophysiological stimuli or genetic modification.It is an"omics"technique that is situated downstream of genomics,transcriptomics and proteomics.Metabolomics is recognized as a promising technique in the field of systems biology for the evaluation of global metabolic changes.During the last decade,metabolomics approaches have become widely used in the study of liver diseases for the detection of early biomarkers and altered metabolic pathways.It is a powerful technique to improve our pathophysiological knowledge of various liver diseases.It can be a useful tool to help clinicians in the diagnostic process especially to distinguish malignant and non-malignant liver disease as well as to determine the etiology or severity of the liver disease.It can also assess therapeutic response or predict drug induced liver injury.Nevertheless,the usefulness of metabolomics is often not understood by clinicians,especially the concept of metabolomics profiling or fingerprinting.In the present work,after a concise description of the different techniques and processes used in metabolomics,we will review the main research on this subject by focusing specifically on in vitro proton nuclear magnetic resonance spectroscopy based metabolomics approaches in human studies.We will first consider the clinical point of view enlighten physicians on this new approach and emphasis its future use in clinical"routine".展开更多
BACKGROUND The evaluation of periportal fibrosis(PPF)is essential for a prognostic assessment of patients with Schistosomiasis mansoni.The WHO Niamey Protocol defines patterns of fibrosis from abdominal ultrasonograph...BACKGROUND The evaluation of periportal fibrosis(PPF)is essential for a prognostic assessment of patients with Schistosomiasis mansoni.The WHO Niamey Protocol defines patterns of fibrosis from abdominal ultrasonography,^(1)H-nuclear magnetic resonance(NMR)-based metabonomics has been employed to assess liver fibrosis in some diseases.AIM To build 1H-NMR-based metabonomics models(MM)to discriminate mild from significant periportal PPF and identify differences in the metabolite profiles.METHODS A prospective cross-sectional study was performed on schistosomiasis patients at a University Hospital in Northeastern Brazil.We evaluated 41 serum samples from 10 patients with mild PPF(C Niamey pattern)and 31 patients with significant PPF(D/E/F Niamey patterns).MM were built using partial least squares-discriminant analysis(PLS-DA)and orthogonal projections to latent structures discriminant analysis(OPLS-DA)formalisms.RESULTS PLS-DA and OPLS-DA resulted in discrimination between mild and significant PPF groups with R2 and Q2 values of 0.80 and 0.38 and 0.72 and 0.42 for each model,respectively.The OPLS-DA model presented accuracy,sensitivity,and specificity values of 92.7%,90.3%,and 100%to discriminate significant PPF.The metabolites identified as responsible by discrimination were:Nacetylglucosamines,alanine,glycolaldehyde,carbohydrates,and valine.CONCLUSION MMs discriminated mild from significant PPF patterns in patients with Schistosomiasis mansoni through identification of differences in serum metabolites profiles.展开更多
Prostate cancer （PCa） is the second most common male cancer worldwide and the fifth leading cause of death from cancer in men. Early detection and risk stratification is the most effective way to improve the surviva...Prostate cancer （PCa） is the second most common male cancer worldwide and the fifth leading cause of death from cancer in men. Early detection and risk stratification is the most effective way to improve the survival of PCa patients. Current PCa biomarkers lack sufficient sensitivity and specificity to cancer. Metabolite biomarkers are evolving as a new diagnostic tool. This review is aimed to evaluate the potential of metabolite biomarkers for early detection, risk assessment, and monitoring of PCa. Of the 154 identified publications, 27 and 38 were original papers on urine and serum metabolomics, respectively. Nuclear magnetic resonance （NMR） is a promising method for measuring concentrations of metabolites in complex samples with good reproducibility, high sensitivity, and simple sample processing. Especially urine-based NMR metabolomics has the potential to be a cost-efficient method for the early detection of PCa, risk stratification, and monitoring treatment eff^cacy.展开更多
Summary:Mechanisms of pruritus are implicated in the dysregulation of the metabolites in the spinal cord.We investigated pruritus behavioral testing in three groups of young adult male C57B1/6 mice,including one group...Summary:Mechanisms of pruritus are implicated in the dysregulation of the metabolites in the spinal cord.We investigated pruritus behavioral testing in three groups of young adult male C57B1/6 mice,including one group treated with normal saline,while the other groups intradermally injected with a-Me-5-HT(histamine-independent pruritogen),compound 48/80(histaminedependent pruritogen)at the nape skin of the neck,respectively.Proton nuclear magnetic resonance spectroscopy(MRS)was used to compare spinal metabolites from the vertebral cervical among three groups,and to study the association of spinal metabolite ratio and pruritus intensity.The MRS-measured N-acetylaspartate-to-myoinositol ratio(NAA/Ins)was significantly correlated with the number of scratches between normal saline group and 48/80 group or a-Me-5-HT group(both P<0.0001),indicating that NAA/Ins may be a robust surrogate marker of histamine-independent/dependent pruritogen.There was significant difference in Glu/Ins between normal saline group and 48/80 group(P=0.017),indicating that Glu/Ins may be a surrogate marker of histamine-dependent pruritogen,while GABA/Ins was highly significantly different between normal saline group and a-Me-5-HT group(P=0.008),suggesting that GABA/Ins may be a surrogate marker of histamineindependent pruritogen.MRS may reflect the extent of pruritus intensity elicited by a-Me-5-HT and compound 48/80 with sensitivity similar to the number of scratches,and above potential markers need to be further validated in pre-clinical and clinical treatment trials.展开更多
Despite recent progress in diagnosis and therapy,gastrointestinal(GI)cancers remain one of the most important causes of death with a poor prognosis due to late diagnosis.Serum tumor markers and detection of occult blo...Despite recent progress in diagnosis and therapy,gastrointestinal(GI)cancers remain one of the most important causes of death with a poor prognosis due to late diagnosis.Serum tumor markers and detection of occult blood in the stool are the current tests used in the clinic of GI cancers;however,these tests are not useful as diagnostic screening since they have low specificity and low sensitivity.Considering that one of the hallmarks of cancer is dysregulated metabolism and metabolomics is an optimal approach to illustrate the metabolic mechanisms that belong to living systems,is now clear that this-omics could open a new way to study cancer.In the last years,nuclear magnetic resonance(NMR)metabolomics has demonstrated to be an optimal approach for diseases’diagnosis nevertheless a few studies focus on the NMR capability to find new biomarkers for early diagnosis of GI cancers.For these reasons in this review,we will give an update on the status of NMR metabolomic studies for the diagnosis and development of GI cancers using biological fluids.展开更多
Ruditapes philippinarum,a clam that thrives in intertidal zones of various salinities,is a useful biomonitor to marine contaminants.We investigated the influence of dilution to 75% and 50% of normal seawater salinity(...Ruditapes philippinarum,a clam that thrives in intertidal zones of various salinities,is a useful biomonitor to marine contaminants.We investigated the influence of dilution to 75% and 50% of normal seawater salinity(31.1) on the responses of the digestive gland of R.philippinarum to arsenic exposure(20 μg/L),using nuclear magnetic resonance(NMR)-based metabolomics.After acute arsenic exposure for 48 h,salinity-dependent differential metabolic responses were detected.In normal seawater,arsenic exposure increased the concentrations of branched-chain amino acids,and of threonine,proline,phosphocholine and adenosine,and it decreased the levels of alanine,hypotaurine,glucose,glycogen and ATP in the digestive glands.Differential changes in metabolic biomarkers observed at lower salinity(～23.3) included elevation of succinate,taurine and ATP,and depletion of branched-chain amino acids,threonine and glutamine.Unique effects of arsenic at the lowest salinity(～15.6) included down-regulation of glutamate,succinate and ADP,and up-regulation of phosphocholine.We conclude that salinity influences the metabolic responses of this clam to arsenic.展开更多
Background: Due to the important functions of arginine in poultry,it should be questioned whether the currently adopted dietary Arg:Lys ratios are sufficient to meet the modern broiler requirement in arginine.The pres...Background: Due to the important functions of arginine in poultry,it should be questioned whether the currently adopted dietary Arg:Lys ratios are sufficient to meet the modern broiler requirement in arginine.The present study aimed,therefore,to evaluate the effects of the dietary supplementation of L-arginine in a commercial broiler diet on productive performance,breast meat quality attributes,incidence and severity of breast muscle myopathies and foot pad dermatitis(FPD),and plasma and muscle metabolomics profile in fast-growing broilers.Results: A total of 1,170 1-day-old Ross 308 male chicks was divided into two experimental groups of 9 replicates each fed either a commercial basal diet(CON,digestible Arg:Lys ratio of 1.05,1.05,1.06 and 1.07 in each feeding phase,respectively) or the same basal diet supplemented on-top with crystalline L-arginine(ARG,digestible Arg:Lys ratio of 1.15,1.15,1.16 and 1.17,respectively).Productive parameters were determined at the end of each feeding phase(12,22,33,43 d).At slaughter(43 d),incidence and severity of FPD and breast myopathies were assessed,while plasma and breast muscle samples were collected and analyzed by proton nuclear magnetic resonancespectroscopy.The dietary supplementation of arginine significantly reduced cumulative feed conversion ratio compared to the control diet at 12 d(1.352 vs.1.401,P < 0.05),22 d(1.398 vs.1.420; P < 0.01) and 33 d(1.494 vs.1.524; P < 0.05),and also tended to improve it in the overall period of trial(1.646 vs.1.675; P = 0.09).Body weight was significantly increased in ARG compared to CON group at 33 d(1,884 vs.1,829 g; P < 0.05).No significant effect was observed on meat quality attributes,breast myopathies and FPD occurrence.ARG birds showed significantly higher plasma concentration of arginine and leucine,and lower of acetoacetate,glutamate,adenosine and proline.Arginine and acetate concentrations were higher,whereas acetone and inosine levels were lower in the breast of ARG birds(P < 0.05).Conclusions: Taken together,these data showed that increased digestible Arg:Lys ratio had positive effects on feed efficiency in broiler chickens probably via modulation of metabolites that play key roles in energy and protein metabolism.展开更多
Drug abuse has become a global problem.The mass spectrometry‑based metabolic consequences of ketamine administration in anesthesia and therapy have been well studied,but to the best of our knowledge,metabolomic studie...Drug abuse has become a global problem.The mass spectrometry‑based metabolic consequences of ketamine administration in anesthesia and therapy have been well studied,but to the best of our knowledge,metabolomic studies of ketamine abuse based on nuclear magnetic resonance(NMR)spectroscopy are still lacking.In this study,twenty Sprague–Dawley rats were randomly assigned into two groups:a control group(n=10)and a ketamine group(n=10).The animals in the ketamine group received intraperitoneal injections of ketamine twice daily at 12‑h intervals at progressively increasing doses over a period of 9 days,while the control group received an equal volume of saline.The urine samples were collected for 24 h at days 0,1,3,5,7,and 9 for the metabolomics study.The metabolic changes in urine after short‑term ketamine administration were analyzed by proton NMR coupled with multivariate statistical analysis.The results indicated that short‑term ketamine exposure led to significant alterations of the metabolites in the urine of the rats.Specifically,1,3,7‑trimethyluric acid,1,3‑dimethyluric acid,acetoacetic acid,acetylglycine,creatine,sarcosine,dimethylglycine,glycine,and theobromine were significantly increased in the urine.Significant changes were also found in metabolites related to antioxidant and energy metabolism,including acetoacetic acid,succinate,1,3,7‑trimethyluric acid,1,3‑dimethyluric acid,creatine,and taurine.Our findings indicated that short‑term ketamine administration leads to disorder of energy metabolism and oxidative stress.In addition,the modified metabolites identified could serve as the new biological markers and potential biological indices reflecting the underlying mechanism of ketamine abuse.展开更多
Metabolomics is a field of study in systems biology that involves the identification and quantification of metabolites present in a biological system. Analyzing metabolic differences between unperturbed and perturbed ...Metabolomics is a field of study in systems biology that involves the identification and quantification of metabolites present in a biological system. Analyzing metabolic differences between unperturbed and perturbed networks, such as cancerous and noncancerous samples, can provide insight into underlying disease pathology, disease prognosis and diagnosis. Despite the large number of review articles concerning metabolomics and its application in cancer research, biomarker and drug discovery, these reviews do not focus on a specific type of cancer. Metabolomics may provide biomarkers useful for identification of early stage gastric cancer, potentially addressing an important clinical need. Here, we present a short review on metabolomics as a tool for biomarker discovery in human gastric cancer, with a primary focus on its use as a predictor of anticancer drug chemosensitivity, diagnosis, prognosis, and metastasis.展开更多
Over one half the patients with rheumatoid arthritis （RA） are being treated with methotrexate （MTX）. Although well proven, the efficacy of MTX varies in individual patients. This study examined the metabolic bioma...Over one half the patients with rheumatoid arthritis （RA） are being treated with methotrexate （MTX）. Although well proven, the efficacy of MTX varies in individual patients. This study examined the metabolic biomarkers that can be used to predict the therapeutic effect of MTX by using metabolomic analysis. Rats were immunized with collagen to rapidly cause collagen-induced arthritis （CIA） and then treated with 0.1 mg/kg MTX for 4 weeks. The clinical signs and the histopathological features of CIA were observed to evaluate the therapeutic effects. Urine samples of CIA rats were collected, and analyzed by using 600 M 1H-nuclear magnetic resonance （1H-NMR） for spectral binning after the therapy. The urine spectra were divided into spectral bins, and 20 endogenous metabolites were assigned by Chenomx Suite. Multivariate analyses were performed to identify the spectral pattern of endogenous metabolites related to MTX therapy. The results showed that the clustering of the spectra of the urine samples from the responsive rats （n=20） was different from that from the non-responsive rats （n=11）. Multivariate analysis showed difference in metabolic profiles between the responsive and non-responsive rats by using partial least squares-discrimination analysis （PLS-DA） （R2=0.812, Q2=0.604）. In targeted profiling, 13 endogenous metabolites （uric acid, taurine, histidine, methionine, glycine, etc.） were selected as putative biomarkers for predicting therapeutic response to MTX. It was suggested that 1H-NMR-based metabolomic analysis can be used to predict the therapeutic effect of MTX, and several metabolites were found to be related to the therapeutic effects of MTX.展开更多
Modern biotechnology, based on recombinant DNA techniques, has made it possible to introduce new traits with great potential for crop improvement. However, concerns about unintended effects of gene transformation that...Modern biotechnology, based on recombinant DNA techniques, has made it possible to introduce new traits with great potential for crop improvement. However, concerns about unintended effects of gene transformation that possibly threaten environment or consumer health have persuaded scientists to set up pre-release tests on genetically modified organisms. Assessment of ＇substantial equivalence＇ concept that established by comparison of genetically modified organism with a comparator with a history of safe use could be the first step of a comprehensive risk assessment. Metabolite level is the dchest in performance of changes which stem from genetic or environmental factors. Since assessment of all metabolites in detail is very costly and practically impossible, statistical evaluation of processed data of grain spectroscopic values could be a time and cost effective substitution for complex chemical analysis. To investigate the ability of multivariate statistical techniques in comparison of metabolomes as well as testing a method for such comparisons with available tools, a transgenic rice in combination with its traditionally bred parent were used as test material, and the discriminant analysis were applied as supervised method and principal component analysis as unsupervised classification method on the processed data which were extracted from Fourier transform infrared spectroscopy and nuclear magnetic resonance spectral data of powdered rice and rice extraction and badey grain samples, of which the latter was considered as control. The results confirmed the capability of statistics, even with initial data processing applications in metabolome studies. Meanwhile, this study confirms that the supervised method results in more distinctive results.展开更多
BACKGROUND Colorectal cancer(CRC),the third most common cause of death in both males and females worldwide,shows a positive response to therapy and usually a better prognosis when detected at an early stage.However,th...BACKGROUND Colorectal cancer(CRC),the third most common cause of death in both males and females worldwide,shows a positive response to therapy and usually a better prognosis when detected at an early stage.However,the survival rate declines when the diagnosis is late and the tumor spreads to other organs.Currently,the measures widely used in the clinic are fecal occult blood test and evaluation of serum tumor markers,but the lack of sensitivity and specificity of these markers restricts their use for CRC diagnosis.Due to its high sensitivity and precision,colonoscopy is currently the gold-standard screening technique for CRC,but it is a costly and invasive procedure.Therefore,the implementation of custom-made methodologies including those with minimal invasiveness,protection,and reproducibility is highly desirable.With regard to other screening methods,the screening of fecal samples has several benefits,and metabolomics is a successful method to classify the metabolite shift in living systems as a reaction to pathophysiological influences,genetic modifications,and environmental factors.AIM To characterize the variation groups and potentially recognize some diagnostic markers,we compared with healthy controls(HCs)the fecal nuclear magnetic resonance(NMR)metabolomic profiles of patients with CRC or adenomatous polyposis(AP).METHODS Proton nuclear magnetic resonance spectroscopy was used in combination with multivariate and univariate statistical approaches,to define the fecal metabolic profiles of 32 CRC patients,16 AP patients,and 38 HCs well matched in age,sex,and body mass index.RESULTS NMR metabolomic analyses revealed that fecal sample profiles differed among CRC patients,AP patients,and HCs,and some discriminatory metabolites including acetate,butyrate,propionate,3-hydroxyphenylacetic acid,valine,tyrosine and leucine were identified.CONCLUSION In conclusion,we are confident that our data can be a forerunner for future studies on CRC management,especially the diagnosis and evaluation of the effectiveness of treatments.展开更多
Molluscan metabolomic analysis is essential for the understanding of the regulatory mechanism of aquatic invertebrate in response to hepatotoxic microcystins(MCs)stress.To understand the system responses of the gastro...Molluscan metabolomic analysis is essential for the understanding of the regulatory mechanism of aquatic invertebrate in response to hepatotoxic microcystins(MCs)stress.To understand the system responses of the gastropod to MC exposure,metabolomic alterations caused by two strains(MC-producing and non MC-producing)of Microcystis aeruginosa were characterized indiff erent biological matrices(hepatopancreas and muscle)of Bellamya aeruginosa(Gastropoda)using 1 H nuclear magnetic resonance(NMR)spectroscopy combined with MCs detections after exposure for 1,7,and 14 d.Although ELISA analysis showed that no MCs was detected in both tissues after non MC-producing M.aeruginosa exposure,MCs concentrations were increasing in the hepatopancreas(from 1.29±0.48μg/g to 3.17±0.11μg/g)and foot muscle(from 0.07±0.02μg/g to 0.21±0.08μg/g)after 14-d exposure of MC-producing M.aeruginosa.Meanwhile,we observed that MC induced signifi cant increase in creatine,a variety of amino acids(leucine,isoleucine,valine,threonine,alanine,methionine,glutamate,aspartate,and lysine),carboxylic acids(lactate,acetate,and D-3-hydroxybutyrate),and choline and its derivatives(phosphocholine and glycerophosphocholine)but decreased the energy substance(lipids,glucose,and glycogen)in the hepatopancreas.However,no signifi cant metabolite diff erences were observed in the muscle between MC-producing and non MC-producing cyanobacteria treated groups.These results suggest that MC exposure may cause hepatic energy expenditure accompanied with various metabolic disorders that involve lipid metabolism,protein catabolism,osmoregulation,glycolysis,glycogenolysis,and tricarboxylic acid(TCA)cycle.Moreover,metabolic perturbation was aggravated as the level of accumulated MCs raised over time in the MC-producing cyanobacteria treatment.These fi ndings indicated that MCs accumulation might lead to oxidative-stress-mediated damage of mitochondria functions.展开更多
Lipoprotein metabolism is markedly altered in chronic kidney disease(CKD).Studies on the association between nuclear magnetic resonance(NMR)derived lipoprotein subfraction signature and mortality in CKD patients under...Lipoprotein metabolism is markedly altered in chronic kidney disease(CKD).Studies on the association between nuclear magnetic resonance(NMR)derived lipoprotein subfraction signature and mortality in CKD patients undergoing hemodialysis are limited.NMR based metabolomics was performed on the baseline plasma samples from 368 maintenance hemodialysis patients.Survival analyses were used to investigate the effect of lipoproteins on all-cause mortality and cardiovascular disease(CVD)mortality.Prediction models were further developed using stepwise regression combined cox proportional-hazards model.During the average follow-up of 45.1 months,we observed 144 all-cause deaths and 67 CVD deaths.After adjustment for 14 important covariates,we identified 18 and 35 lipoprotein parameters associated with all-cause mortality and CVD mortality,separately.Cholesterol in total low-density lipoprotein(LDL-C)and total high-density lipoprotein(HDL-C)were correlated with neither all-cause death nor CVD death.For lipoprotein subfractions,triglyceride levels in large very-low density lipoprotein(VLDL)were positively correlated only with all-cause mortality.Lipids(triglyceride,cholesterol and phospholipid)in medium VLDL,cholesterol/total lipids in intermediate-density lipoprotein(IDL)and free cholesterol/total lipids in small high-density lipoprotein(HDL)were positively associated with both all-cause and CVD mortality.The addition of lipoprotein parameters to traditional risk factors significantly improved the mortality risk prediction:the area under the receiver operating characteristic curve(AUC)was improved from 0.811 to 0.842(p-value=0.020)for all-cause mortality and 0.806 to 0.854(p-value=0.005)for CVD mortality.Our results highlight the lipoprotein subfractions related to all-cause and CVD mortality of maintenance hemodialysis patients,and the lipoproteins-driven prediction models significantly outperform traditional risk factors.展开更多
基金Supported by the National Natural Science Foundation of China,No.81471729 and No.81101102the Science and Technology and Planning Project of Guangdong Province,No.2016A020216025+2 种基金the Research Award Fund for Outstanding Young Teachers in Higher Education Institutions,Guangdong Province,No.YQ2015245the National Natural Science Foundation of Guangdong Province,No.S2011010004973the Department of Education of Guangdong Province,No.2017KTSCX071
文摘BACKGROUND Several studies have demonstrated a correlation between esophageal cancer(EC)and perturbed urinary metabolomic profiles,but none has described the correlation between urine metabolite profiles and those of the tumor and adjacent esophageal mucosa in the same patient.AIM To investigate how urinary metabolic phenotypes were linked to the changes in the biochemical landscape of esophageal tumors.METHODS Nuclear magnetic resonance-based metabolomics were applied to esophageal tumor tissues and adjacent normal mucosal tissues alongside patient-matched urine samples.RESULTS Analysis revealed that specific metabolite changes overlapped across both metrics,including glucose,glutamate,citrate,glycine,creatinine and taurine,indicating that the networks for metabolic pathway perturbations in EC,potentially involved in but not limited to disruption of fatty acid metabolism,glucose and glycolytic metabolism,tricarboxylic acid cycle and glutaminolysis.Additionally,changes in most urinary biomarkers correlated with changes in biomarker candidates in EC tissues,implying enhanced energy production for rapid cell proliferation.CONCLUSION Overall,these associations provide evidence for distinct metabolic signatures and pathway disturbances between the tumor tissues and urine of EC patients,and changes in urinary metabolic signature could reflect reprogramming of the aforementioned metabolic pathways in EC tissues.Further investigation is needed to validate these initial findings using larger samples and to establish the underlying mechanism of EC progression.
基金National Natural Science Foundation of China(82170701,82370700).
文摘Acute kidney injury(AKI)is a significant risk factor for chronic kidney disease(CKD),yet the mechanisms driving this progression remain unclear(Kellum et al.2021).Given the kidney's role in homeostasis,AKI profoundly impacts systemic health,often leading to CKD,characterized by persistent damage or reduced glomerular filtration rate(GFR)(Stevens et al.2024).The high incidence of AKI and its strong association with subsequent CKD necessitates a deeper understanding of the transition process.
文摘AIM To develop metabonomic models(MMs), using 1 H nuclear magnetic resonance(NMR) spectra of serum, to predict significant liver fibrosis(SF: Metavir ≥ F2), advanced liver fibrosis(AF: METAVIR ≥ F3) and cirrhosis(C: METAVIR = F4 or clinical cirrhosis) in chronic hepatitis C(CHC) patients. Additionally, to compare the accuracy of the MMs with the aspartate aminotransferase to platelet ratio index(APRI) and fibrosis index based on four factors(FIB-4). METHODS Sixty-nine patients who had undergone biopsy in the previous 12 mo or had clinical cirrhosis were included. The presence of any other liver disease was a criterion for exclusion. The MMs, constructed using partial least squares discriminant analysis and linear discriminant analysis formalisms, were tested by cross-validation, considering SF, AF and C. RESULTS Results showed that forty-two patients(61%) presented SF, 28(40%) AF and 18(26%) C. The MMs showed sensitivity and specificity of 97.6% and 92.6% to predict SF; 96.4% and 95.1% to predict AF; and 100% and 98.0% to predict C. Besides that, the MMs correctly classified all 27(39.7%) and 25(38.8%) patients with intermediate values of APRI and FIB-4, respectively. CONCLUSION The metabonomic strategy performed excellently in predicting significant and advanced liver fibrosis in CHC patients, including those in the gray zone of APRI and FIB-4, which may contribute to reducing the need for these patients to undergo liver biopsy.
文摘Metabolomics is defined as the quantitative measurement of the dynamic multiparametric metabolic response of living systems to pathophysiological stimuli or genetic modification.It is an"omics"technique that is situated downstream of genomics,transcriptomics and proteomics.Metabolomics is recognized as a promising technique in the field of systems biology for the evaluation of global metabolic changes.During the last decade,metabolomics approaches have become widely used in the study of liver diseases for the detection of early biomarkers and altered metabolic pathways.It is a powerful technique to improve our pathophysiological knowledge of various liver diseases.It can be a useful tool to help clinicians in the diagnostic process especially to distinguish malignant and non-malignant liver disease as well as to determine the etiology or severity of the liver disease.It can also assess therapeutic response or predict drug induced liver injury.Nevertheless,the usefulness of metabolomics is often not understood by clinicians,especially the concept of metabolomics profiling or fingerprinting.In the present work,after a concise description of the different techniques and processes used in metabolomics,we will review the main research on this subject by focusing specifically on in vitro proton nuclear magnetic resonance spectroscopy based metabolomics approaches in human studies.We will first consider the clinical point of view enlighten physicians on this new approach and emphasis its future use in clinical"routine".
文摘BACKGROUND The evaluation of periportal fibrosis(PPF)is essential for a prognostic assessment of patients with Schistosomiasis mansoni.The WHO Niamey Protocol defines patterns of fibrosis from abdominal ultrasonography,^(1)H-nuclear magnetic resonance(NMR)-based metabonomics has been employed to assess liver fibrosis in some diseases.AIM To build 1H-NMR-based metabonomics models(MM)to discriminate mild from significant periportal PPF and identify differences in the metabolite profiles.METHODS A prospective cross-sectional study was performed on schistosomiasis patients at a University Hospital in Northeastern Brazil.We evaluated 41 serum samples from 10 patients with mild PPF(C Niamey pattern)and 31 patients with significant PPF(D/E/F Niamey patterns).MM were built using partial least squares-discriminant analysis(PLS-DA)and orthogonal projections to latent structures discriminant analysis(OPLS-DA)formalisms.RESULTS PLS-DA and OPLS-DA resulted in discrimination between mild and significant PPF groups with R2 and Q2 values of 0.80 and 0.38 and 0.72 and 0.42 for each model,respectively.The OPLS-DA model presented accuracy,sensitivity,and specificity values of 92.7%,90.3%,and 100%to discriminate significant PPF.The metabolites identified as responsible by discrimination were:Nacetylglucosamines,alanine,glycolaldehyde,carbohydrates,and valine.CONCLUSION MMs discriminated mild from significant PPF patterns in patients with Schistosomiasis mansoni through identification of differences in serum metabolites profiles.
基金Project supported by the Joint Research Project(No.PW2016D-13)of Pudong New Area Health and Family Planning Committee,Shanghai,China
文摘Prostate cancer （PCa） is the second most common male cancer worldwide and the fifth leading cause of death from cancer in men. Early detection and risk stratification is the most effective way to improve the survival of PCa patients. Current PCa biomarkers lack sufficient sensitivity and specificity to cancer. Metabolite biomarkers are evolving as a new diagnostic tool. This review is aimed to evaluate the potential of metabolite biomarkers for early detection, risk assessment, and monitoring of PCa. Of the 154 identified publications, 27 and 38 were original papers on urine and serum metabolomics, respectively. Nuclear magnetic resonance （NMR） is a promising method for measuring concentrations of metabolites in complex samples with good reproducibility, high sensitivity, and simple sample processing. Especially urine-based NMR metabolomics has the potential to be a cost-efficient method for the early detection of PCa, risk stratification, and monitoring treatment eff^cacy.
基金This work was supported by grants from the National Natural Science Foundation of China(No.81670240 and No.81873467)the Medical Innovation Project in Fujian Province(No.2017-CX-48).
文摘Summary:Mechanisms of pruritus are implicated in the dysregulation of the metabolites in the spinal cord.We investigated pruritus behavioral testing in three groups of young adult male C57B1/6 mice,including one group treated with normal saline,while the other groups intradermally injected with a-Me-5-HT(histamine-independent pruritogen),compound 48/80(histaminedependent pruritogen)at the nape skin of the neck,respectively.Proton nuclear magnetic resonance spectroscopy(MRS)was used to compare spinal metabolites from the vertebral cervical among three groups,and to study the association of spinal metabolite ratio and pruritus intensity.The MRS-measured N-acetylaspartate-to-myoinositol ratio(NAA/Ins)was significantly correlated with the number of scratches between normal saline group and 48/80 group or a-Me-5-HT group(both P<0.0001),indicating that NAA/Ins may be a robust surrogate marker of histamine-independent/dependent pruritogen.There was significant difference in Glu/Ins between normal saline group and 48/80 group(P=0.017),indicating that Glu/Ins may be a surrogate marker of histamine-dependent pruritogen,while GABA/Ins was highly significantly different between normal saline group and a-Me-5-HT group(P=0.008),suggesting that GABA/Ins may be a surrogate marker of histamineindependent pruritogen.MRS may reflect the extent of pruritus intensity elicited by a-Me-5-HT and compound 48/80 with sensitivity similar to the number of scratches,and above potential markers need to be further validated in pre-clinical and clinical treatment trials.
基金Supported by Foundation“Ente Cassa di Risparmio di Firenze”,No.FCR 2017Italian Ministry of Health,Ricerca Finalizzata 2016,No.FR-2016-02361616。
文摘Despite recent progress in diagnosis and therapy,gastrointestinal(GI)cancers remain one of the most important causes of death with a poor prognosis due to late diagnosis.Serum tumor markers and detection of occult blood in the stool are the current tests used in the clinic of GI cancers;however,these tests are not useful as diagnostic screening since they have low specificity and low sensitivity.Considering that one of the hallmarks of cancer is dysregulated metabolism and metabolomics is an optimal approach to illustrate the metabolic mechanisms that belong to living systems,is now clear that this-omics could open a new way to study cancer.In the last years,nuclear magnetic resonance(NMR)metabolomics has demonstrated to be an optimal approach for diseases’diagnosis nevertheless a few studies focus on the NMR capability to find new biomarkers for early diagnosis of GI cancers.For these reasons in this review,we will give an update on the status of NMR metabolomic studies for the diagnosis and development of GI cancers using biological fluids.
基金Supported by the National Natural Science Foundation of China(No.41106102)Natural Science Foundation of Shandong Province(No.ZR2009CZ008)the 100 Talents Program of Chinese Academy of Sciences
文摘Ruditapes philippinarum,a clam that thrives in intertidal zones of various salinities,is a useful biomonitor to marine contaminants.We investigated the influence of dilution to 75% and 50% of normal seawater salinity(31.1) on the responses of the digestive gland of R.philippinarum to arsenic exposure(20 μg/L),using nuclear magnetic resonance(NMR)-based metabolomics.After acute arsenic exposure for 48 h,salinity-dependent differential metabolic responses were detected.In normal seawater,arsenic exposure increased the concentrations of branched-chain amino acids,and of threonine,proline,phosphocholine and adenosine,and it decreased the levels of alanine,hypotaurine,glucose,glycogen and ATP in the digestive glands.Differential changes in metabolic biomarkers observed at lower salinity(～23.3) included elevation of succinate,taurine and ATP,and depletion of branched-chain amino acids,threonine and glutamine.Unique effects of arsenic at the lowest salinity(～15.6) included down-regulation of glutamate,succinate and ADP,and up-regulation of phosphocholine.We conclude that salinity influences the metabolic responses of this clam to arsenic.
文摘Background: Due to the important functions of arginine in poultry,it should be questioned whether the currently adopted dietary Arg:Lys ratios are sufficient to meet the modern broiler requirement in arginine.The present study aimed,therefore,to evaluate the effects of the dietary supplementation of L-arginine in a commercial broiler diet on productive performance,breast meat quality attributes,incidence and severity of breast muscle myopathies and foot pad dermatitis(FPD),and plasma and muscle metabolomics profile in fast-growing broilers.Results: A total of 1,170 1-day-old Ross 308 male chicks was divided into two experimental groups of 9 replicates each fed either a commercial basal diet(CON,digestible Arg:Lys ratio of 1.05,1.05,1.06 and 1.07 in each feeding phase,respectively) or the same basal diet supplemented on-top with crystalline L-arginine(ARG,digestible Arg:Lys ratio of 1.15,1.15,1.16 and 1.17,respectively).Productive parameters were determined at the end of each feeding phase(12,22,33,43 d).At slaughter(43 d),incidence and severity of FPD and breast myopathies were assessed,while plasma and breast muscle samples were collected and analyzed by proton nuclear magnetic resonancespectroscopy.The dietary supplementation of arginine significantly reduced cumulative feed conversion ratio compared to the control diet at 12 d(1.352 vs.1.401,P < 0.05),22 d(1.398 vs.1.420; P < 0.01) and 33 d(1.494 vs.1.524; P < 0.05),and also tended to improve it in the overall period of trial(1.646 vs.1.675; P = 0.09).Body weight was significantly increased in ARG compared to CON group at 33 d(1,884 vs.1,829 g; P < 0.05).No significant effect was observed on meat quality attributes,breast myopathies and FPD occurrence.ARG birds showed significantly higher plasma concentration of arginine and leucine,and lower of acetoacetate,glutamate,adenosine and proline.Arginine and acetate concentrations were higher,whereas acetone and inosine levels were lower in the breast of ARG birds(P < 0.05).Conclusions: Taken together,these data showed that increased digestible Arg:Lys ratio had positive effects on feed efficiency in broiler chickens probably via modulation of metabolites that play key roles in energy and protein metabolism.
基金The Project of the National Natural Sciences Foundation of China(81373239,30973369).
文摘Drug abuse has become a global problem.The mass spectrometry‑based metabolic consequences of ketamine administration in anesthesia and therapy have been well studied,but to the best of our knowledge,metabolomic studies of ketamine abuse based on nuclear magnetic resonance(NMR)spectroscopy are still lacking.In this study,twenty Sprague–Dawley rats were randomly assigned into two groups:a control group(n=10)and a ketamine group(n=10).The animals in the ketamine group received intraperitoneal injections of ketamine twice daily at 12‑h intervals at progressively increasing doses over a period of 9 days,while the control group received an equal volume of saline.The urine samples were collected for 24 h at days 0,1,3,5,7,and 9 for the metabolomics study.The metabolic changes in urine after short‑term ketamine administration were analyzed by proton NMR coupled with multivariate statistical analysis.The results indicated that short‑term ketamine exposure led to significant alterations of the metabolites in the urine of the rats.Specifically,1,3,7‑trimethyluric acid,1,3‑dimethyluric acid,acetoacetic acid,acetylglycine,creatine,sarcosine,dimethylglycine,glycine,and theobromine were significantly increased in the urine.Significant changes were also found in metabolites related to antioxidant and energy metabolism,including acetoacetic acid,succinate,1,3,7‑trimethyluric acid,1,3‑dimethyluric acid,creatine,and taurine.Our findings indicated that short‑term ketamine administration leads to disorder of energy metabolism and oxidative stress.In addition,the modified metabolites identified could serve as the new biological markers and potential biological indices reflecting the underlying mechanism of ketamine abuse.
基金Supported by Research Council of Norway,NO.70174300
文摘Metabolomics is a field of study in systems biology that involves the identification and quantification of metabolites present in a biological system. Analyzing metabolic differences between unperturbed and perturbed networks, such as cancerous and noncancerous samples, can provide insight into underlying disease pathology, disease prognosis and diagnosis. Despite the large number of review articles concerning metabolomics and its application in cancer research, biomarker and drug discovery, these reviews do not focus on a specific type of cancer. Metabolomics may provide biomarkers useful for identification of early stage gastric cancer, potentially addressing an important clinical need. Here, we present a short review on metabolomics as a tool for biomarker discovery in human gastric cancer, with a primary focus on its use as a predictor of anticancer drug chemosensitivity, diagnosis, prognosis, and metastasis.
文摘Over one half the patients with rheumatoid arthritis （RA） are being treated with methotrexate （MTX）. Although well proven, the efficacy of MTX varies in individual patients. This study examined the metabolic biomarkers that can be used to predict the therapeutic effect of MTX by using metabolomic analysis. Rats were immunized with collagen to rapidly cause collagen-induced arthritis （CIA） and then treated with 0.1 mg/kg MTX for 4 weeks. The clinical signs and the histopathological features of CIA were observed to evaluate the therapeutic effects. Urine samples of CIA rats were collected, and analyzed by using 600 M 1H-nuclear magnetic resonance （1H-NMR） for spectral binning after the therapy. The urine spectra were divided into spectral bins, and 20 endogenous metabolites were assigned by Chenomx Suite. Multivariate analyses were performed to identify the spectral pattern of endogenous metabolites related to MTX therapy. The results showed that the clustering of the spectra of the urine samples from the responsive rats （n=20） was different from that from the non-responsive rats （n=11）. Multivariate analysis showed difference in metabolic profiles between the responsive and non-responsive rats by using partial least squares-discrimination analysis （PLS-DA） （R2=0.812, Q2=0.604）. In targeted profiling, 13 endogenous metabolites （uric acid, taurine, histidine, methionine, glycine, etc.） were selected as putative biomarkers for predicting therapeutic response to MTX. It was suggested that 1H-NMR-based metabolomic analysis can be used to predict the therapeutic effect of MTX, and several metabolites were found to be related to the therapeutic effects of MTX.
文摘Modern biotechnology, based on recombinant DNA techniques, has made it possible to introduce new traits with great potential for crop improvement. However, concerns about unintended effects of gene transformation that possibly threaten environment or consumer health have persuaded scientists to set up pre-release tests on genetically modified organisms. Assessment of ＇substantial equivalence＇ concept that established by comparison of genetically modified organism with a comparator with a history of safe use could be the first step of a comprehensive risk assessment. Metabolite level is the dchest in performance of changes which stem from genetic or environmental factors. Since assessment of all metabolites in detail is very costly and practically impossible, statistical evaluation of processed data of grain spectroscopic values could be a time and cost effective substitution for complex chemical analysis. To investigate the ability of multivariate statistical techniques in comparison of metabolomes as well as testing a method for such comparisons with available tools, a transgenic rice in combination with its traditionally bred parent were used as test material, and the discriminant analysis were applied as supervised method and principal component analysis as unsupervised classification method on the processed data which were extracted from Fourier transform infrared spectroscopy and nuclear magnetic resonance spectral data of powdered rice and rice extraction and badey grain samples, of which the latter was considered as control. The results confirmed the capability of statistics, even with initial data processing applications in metabolome studies. Meanwhile, this study confirms that the supervised method results in more distinctive results.
文摘BACKGROUND Colorectal cancer(CRC),the third most common cause of death in both males and females worldwide,shows a positive response to therapy and usually a better prognosis when detected at an early stage.However,the survival rate declines when the diagnosis is late and the tumor spreads to other organs.Currently,the measures widely used in the clinic are fecal occult blood test and evaluation of serum tumor markers,but the lack of sensitivity and specificity of these markers restricts their use for CRC diagnosis.Due to its high sensitivity and precision,colonoscopy is currently the gold-standard screening technique for CRC,but it is a costly and invasive procedure.Therefore,the implementation of custom-made methodologies including those with minimal invasiveness,protection,and reproducibility is highly desirable.With regard to other screening methods,the screening of fecal samples has several benefits,and metabolomics is a successful method to classify the metabolite shift in living systems as a reaction to pathophysiological influences,genetic modifications,and environmental factors.AIM To characterize the variation groups and potentially recognize some diagnostic markers,we compared with healthy controls(HCs)the fecal nuclear magnetic resonance(NMR)metabolomic profiles of patients with CRC or adenomatous polyposis(AP).METHODS Proton nuclear magnetic resonance spectroscopy was used in combination with multivariate and univariate statistical approaches,to define the fecal metabolic profiles of 32 CRC patients,16 AP patients,and 38 HCs well matched in age,sex,and body mass index.RESULTS NMR metabolomic analyses revealed that fecal sample profiles differed among CRC patients,AP patients,and HCs,and some discriminatory metabolites including acetate,butyrate,propionate,3-hydroxyphenylacetic acid,valine,tyrosine and leucine were identified.CONCLUSION In conclusion,we are confident that our data can be a forerunner for future studies on CRC management,especially the diagnosis and evaluation of the effectiveness of treatments.
基金Supported by the National Natural Science Foundation of China(Nos.42077219,31302192)the Natural Science Foundation of Zhejiang Province(No.LQ20C190003)+2 种基金the Ningbo Municipal Natural Science Foundation(No.2019A610421)the Ningbo Public Welfare Technology Application Research Project(No.202002N3049)the Hangzhou Municipal Agriculture and Social Development Project(No.2020ZDSJ0697),the Fundamental Research Funds for the Provincial Universities of Zhejiang(No.SJLY2020011),and the K.C.Wong Magna Fund in Ningbo University。
文摘Molluscan metabolomic analysis is essential for the understanding of the regulatory mechanism of aquatic invertebrate in response to hepatotoxic microcystins(MCs)stress.To understand the system responses of the gastropod to MC exposure,metabolomic alterations caused by two strains(MC-producing and non MC-producing)of Microcystis aeruginosa were characterized indiff erent biological matrices(hepatopancreas and muscle)of Bellamya aeruginosa(Gastropoda)using 1 H nuclear magnetic resonance(NMR)spectroscopy combined with MCs detections after exposure for 1,7,and 14 d.Although ELISA analysis showed that no MCs was detected in both tissues after non MC-producing M.aeruginosa exposure,MCs concentrations were increasing in the hepatopancreas(from 1.29±0.48μg/g to 3.17±0.11μg/g)and foot muscle(from 0.07±0.02μg/g to 0.21±0.08μg/g)after 14-d exposure of MC-producing M.aeruginosa.Meanwhile,we observed that MC induced signifi cant increase in creatine,a variety of amino acids(leucine,isoleucine,valine,threonine,alanine,methionine,glutamate,aspartate,and lysine),carboxylic acids(lactate,acetate,and D-3-hydroxybutyrate),and choline and its derivatives(phosphocholine and glycerophosphocholine)but decreased the energy substance(lipids,glucose,and glycogen)in the hepatopancreas.However,no signifi cant metabolite diff erences were observed in the muscle between MC-producing and non MC-producing cyanobacteria treated groups.These results suggest that MC exposure may cause hepatic energy expenditure accompanied with various metabolic disorders that involve lipid metabolism,protein catabolism,osmoregulation,glycolysis,glycogenolysis,and tricarboxylic acid(TCA)cycle.Moreover,metabolic perturbation was aggravated as the level of accumulated MCs raised over time in the MC-producing cyanobacteria treatment.These fi ndings indicated that MCs accumulation might lead to oxidative-stress-mediated damage of mitochondria functions.
基金supported by the National Natural Science Foundation of China(82170752)Shanghai Municipal Health Commission(202140272)+2 种基金National Key R&D Program of China(2022YFC3400700,2022YFA0806400,2020YFE0201600)Shanghai Clinical Research Center for Kidney Disease(22MC1940100)Shanghai Municipal Science and Technology Major Project(2017SHZDZX01).
文摘Lipoprotein metabolism is markedly altered in chronic kidney disease(CKD).Studies on the association between nuclear magnetic resonance(NMR)derived lipoprotein subfraction signature and mortality in CKD patients undergoing hemodialysis are limited.NMR based metabolomics was performed on the baseline plasma samples from 368 maintenance hemodialysis patients.Survival analyses were used to investigate the effect of lipoproteins on all-cause mortality and cardiovascular disease(CVD)mortality.Prediction models were further developed using stepwise regression combined cox proportional-hazards model.During the average follow-up of 45.1 months,we observed 144 all-cause deaths and 67 CVD deaths.After adjustment for 14 important covariates,we identified 18 and 35 lipoprotein parameters associated with all-cause mortality and CVD mortality,separately.Cholesterol in total low-density lipoprotein(LDL-C)and total high-density lipoprotein(HDL-C)were correlated with neither all-cause death nor CVD death.For lipoprotein subfractions,triglyceride levels in large very-low density lipoprotein(VLDL)were positively correlated only with all-cause mortality.Lipids(triglyceride,cholesterol and phospholipid)in medium VLDL,cholesterol/total lipids in intermediate-density lipoprotein(IDL)and free cholesterol/total lipids in small high-density lipoprotein(HDL)were positively associated with both all-cause and CVD mortality.The addition of lipoprotein parameters to traditional risk factors significantly improved the mortality risk prediction:the area under the receiver operating characteristic curve(AUC)was improved from 0.811 to 0.842(p-value=0.020)for all-cause mortality and 0.806 to 0.854(p-value=0.005)for CVD mortality.Our results highlight the lipoprotein subfractions related to all-cause and CVD mortality of maintenance hemodialysis patients,and the lipoproteins-driven prediction models significantly outperform traditional risk factors.
