Kidney disease is a leading cause of death worldwide.Currently,the diagnosis of kidney diseases and the grading of their severity are mainly based on clinical features,which do not reveal the underlying molecular path...Kidney disease is a leading cause of death worldwide.Currently,the diagnosis of kidney diseases and the grading of their severity are mainly based on clinical features,which do not reveal the underlying molecular pathways.More recent surge of∼omics studies has greatly catalyzed disease research.The advent of artificial intelligence(AI)has opened the avenue for the efficient integration and interpretation of big datasets for discovering clinically actionable knowledge.This review discusses how AI and multi-omics can be applied and integrated,to offer opportunities to develop novel diagnostic and therapeutic means in kidney diseases.The combination of new technology and novel analysis pipelines can lead to breakthroughs in expanding our understanding of disease pathogenesis,shedding new light on biomarkers and disease classification,as well as providing possibilities of precise treatment.展开更多
Background Chronic kidney disease (CKD) is a common disorder associated with multiple adverse clinical consequences,especially cardiovascular risk and end-stage renal disease.A recent national survey demonstrated th...Background Chronic kidney disease (CKD) is a common disorder associated with multiple adverse clinical consequences,especially cardiovascular risk and end-stage renal disease.A recent national survey demonstrated that CKD has become a leading health problem in China.There is an urgent need to implement an in-depth investigation of the CKD burden and also to explore underlying mechanisms of CKD progression and it association with adverse consequences.Methods The Chinese Cohort Study of Chronic Kidney Disease (C-STRIDE) is the first national CKD cohort in China.It will enroll approximately 3 000 pre-dialysis CKD patients aged between 18 and 74 years and follow-up for at least 5 years.Questionnaires,anthropometric measures,laboratory tests,and biomaterials will be collected at baseline and annually.The principal clinical outcomes of the C-STRIDE consist of renal disease events,cardiovascular events,and death.Based on the longitudinal clinical data and biomaterials,the risk factors with CKD progression and other outcomes will be analyzed,and candidate markers and predicted models will be established.Conclusion The C-STRIDE would provide important evidence for underlying mechanisms of CKD progression,valuable information for clinical guidelines,and healthcare policies in China.展开更多
Background: Although that glomerulonephritis is the major cause of end-stage renal disease in developing countries such as China, the increasing prevalence of diabetes has contributed to the changing spectrum of pred...Background: Although that glomerulonephritis is the major cause of end-stage renal disease in developing countries such as China, the increasing prevalence of diabetes has contributed to the changing spectrum of predialysis chronic kidney disease. Recent studies have revealed an increased proportion of patients with diabetic kidney disease (DKD) in hemodialysis populations in large cities in China. However, studies regarding the clinical phenotype of DKD in China are extremely limited. The incidence, development, and prognosis of diabetic kidney disease (INDEED) study aims to investigate the incidence, progression, and prognosis of DKD, as well as the associated genetic, behavioral, and environmental factors and biomarkers in patients with DKD in China. Methods: INDEED study is a prospective cohort study based on all participants with diabetes in the Kailuan study, which is a general population-based cohort study in northern China. Altogether, over 10,000 participants with diabetes will be followed biennially. Questionnaires documenting general characteristics, behavioral and environmental factors, and medical history will be administrated. Anthropometric measurements and a series of laboratory tests will be peribrmed in one central laboratory. The DNA, plasma, and urine samples of every participant will be stored in a biobank for future research. Conclusions: INDEED study will provide essential information regarding the clinical phenotype and prognosis of patients with DKD in China and will be valuable to identity factors and biomarkers associated with patients with DKD in China.展开更多
For the past decades,the rapid growth of economy and transition of lifestyles have led to a rapid rise in the prevalence of diabetes in China.Due to the lack of standard process in prevention and management of diabeti...For the past decades,the rapid growth of economy and transition of lifestyles have led to a rapid rise in the prevalence of diabetes in China.Due to the lack of standard process in prevention and management of diabetic kidney disease(DKD)in China,the Peking University Health Science Center organized experts in fields of nephrology and endocrinology to develop the Chinese consensus statement of DKD.This consensus emphasizes on evidence-based inquiry,and focuses on the following three topics:(1)risk factors of the incidence and progression of DKD;(2)the diagnosis of DKD and indication of renal biopsy;(3)the overall management of DKD.展开更多
To the Editor:Diabetic kidney disease(DKD)is the leading cause of the end-stage renal disease nowadays.[1]The etiology of DKD is complex and remains largely unknown.[2]A genome-wide association study showed that a com...To the Editor:Diabetic kidney disease(DKD)is the leading cause of the end-stage renal disease nowadays.[1]The etiology of DKD is complex and remains largely unknown.[2]A genome-wide association study showed that a common missense variant in COL4A3,rs55703767,played a protective role in DKD in type 1 diabetes mellitus in Europeans,and this effect depended on blood glucose levels.[3]However,data from type 2 diabetes mellitus(T2DM)are insufficient.展开更多
The development of a wearable,easy-to-fabricate,and stable intelligent minisystem is highly desired for the closedloop management of diabetes.Conventional systems always suffer from large size,high cost,low stability,...The development of a wearable,easy-to-fabricate,and stable intelligent minisystem is highly desired for the closedloop management of diabetes.Conventional systems always suffer from large size,high cost,low stability,or complex fabrication.Here,we show for the first time a wearable,rapidly manufacturable,stability-enhancing microneedle patch for diabetes management.The patch consists of a graphene composite ink-printed sensor on hollow microneedles,a polyethylene glycol(PEG)-functionalized electroosmotic micropump integrated with the microneedles,and a printed circuit board for precise and intelligent control of the sensor and pump to detect interstitial glucose and deliver insulin through the hollow channels.Via synthesizing and printing the graphene composite ink,the sensor fabrication process is fast and the sensing electrodes are stable.The PEG functionalization enables the micropump a significantly higher stability in delivering insulin,extending its lifetime from days to weeks.The patch successfully demonstrated excellent blood glucose control in diabetic rats.This work may introduce a new paradigm for building new closedloop systems and shows great promise for widespread use in patients with diabetes.展开更多
Background:High levels of plasma homocysteine occur almost uniformly in patients with end-stage renal disease(ESRD).IgA nephropathy(IgAN)is the most common form of primary glomerulonephritis and a common cause of ESRD...Background:High levels of plasma homocysteine occur almost uniformly in patients with end-stage renal disease(ESRD).IgA nephropathy(IgAN)is the most common form of primary glomerulonephritis and a common cause of ESRD in young adults.Here,we aimed to detect whether homocysteine was elevated and associated with clinical-pathologic manifestations of IgAN patients and tested its causal effects using a two-sample Mendelian randomization(MR)approach.Methods:For observational analysis,108 IgAN patients,30 lupus nephritis(LN)patients,50 minimal change disease(MCD)patients,and 206 healthy controls were recruited from April 2014 to April 2015.Their plasma homocysteine was measured and clinical-pathologic manifestations were collected from medical records.For MR analysis,we further included 1686 IgAN patients.The missense variant methylenetetrahydrofolate reductase C677T(rs1801133)was selected as an instrument,which was genotyped by TaqMan allele discrimination assays.Results:Majority of IgAN patients(93.52%,101/108)showed elevated levels of plasma homocysteine(>10μmol/L).Plasma homocysteine in IgAN patients was significantly higher than that in MCD patients(median:18.32 vs.11.15μmol/L,Z=-5.29,P<0.01)and in healthy controls(median:18.32 vs.10.00μmol/L,Z=-8.76,P<0.01),but comparable with those in LN patients(median:18.32 L vs.14.50μmol/L,Z=-1.32,P=0.19).Significant differences were observed in sub-groups of IgAN patients according to quartiles of plasma homocysteine for male ratio(22.22%vs.51.85%vs.70.37%vs.70.37%,χ2=14.29,P<0.01),serum creatinine(median:77.00 vs.100.00 vs.129.00 vs.150.00μmol/L,χ2=34.06,P<0.01),estimated glomerular filtration rate(median:100.52 vs.74.23 vs.52.68 vs.42.67 mL·min-1·1.73 m-2,χ2=21.75,P<0.01),systolic blood pressure(median:120.00 vs.120.00 vs.125.00 vs.130.00 mmHg,χ2=2.97,P=0.05),diastolic blood pressure(median 80.00 vs.75.00 vs.80.00 vs.81.00 mmHg,χ2=11.47,P<0.01),and pathologic tubular atrophy and interstitial fibrosis(T)(T0/T1/T2:62.96%/33.33%/3.70%vs.29.63%/40.74%/29.63%vs.24.00%/48.00%/28.00%vs.14.81%/37.04%/48.15%,χ2=17.66,P<0.01).The coefficient of each rs1801133-T allele on homocysteine levels after controlling age and sex was 7.12(P<0.01).MR estimates showed causal positive effects of homocysteine on serum creatine(β=0.76,P=0.02),systolic blood pressure(β=0.26,P=0.02),diastolic blood pressure(β=0.20,P=0.01),and pathologic T lesion(β=0.01,P=0.01)in IgAN.Conclusions:By observational and MR analyses,consistent results were observed for associations of plasma homocysteine with serum creatinine,blood pressures,and pathologic T lesion in IgAN patients.展开更多
Background:Hyperphosphatemia is a risk factor associated with mortality in patients on maintenance hemodialysis.Gut absorption of phosphate is the major source.Recent studies indicated that the intestinal flora of ure...Background:Hyperphosphatemia is a risk factor associated with mortality in patients on maintenance hemodialysis.Gut absorption of phosphate is the major source.Recent studies indicated that the intestinal flora of uremic patients changed a lot compared with the healthy population,and phosphorus is an essential element of bacterial survival and reproduction.The purpose of this study was to explore the role of intestinal microbiota in phosphorus metabolism. Methods:A prospective self-control study was performed from October 2015 to January 2016.Microbial DNA was isolated from the stools of 20 healthy controls and 21 maintenance hemodialysis patients.Fourteen out of the 21 patients were treated with lanthanum carbonate for 12 weeks.Thus,stools were also collected before and after the treatment.The bacterial composition was analyzed based on 16S ribosomal RNA pyrosequencing.Bioinformatics tools,including sequence alignment,abundance profiling,and taxonomic diversity, were used in microbiome data analyses.Correlations between genera and the serum phosphorus were detected with Pearson's correlation. For visualization of the internal interactions and further measurement of the microbial community,SparCC was used to calculate the Spearman correlation coefficient with the corresponding P value between each two genera. Results:Thirteen genera closely correlated with serum phosphorus and the correlation coefficient was above 0.4(P <0.05).We also found that 58 bacterial operational taxonomic units (OTUs)were significantly different and more decreased OTUs were identified and seven genera (P <0.05)were obviously reduced after using the phosphate binder.Meanwhile,the microbial richness and diversity presented downward trend in hemodialysis patients compared with healthy controls and more downward trend after phosphorus reduction.The co-occurrence network of genera revealed that the network complexity of hemodialysis patients was significantly higher than that of controls,whereas treatment with lanthanum carbonate reduced the network complexity. Conclusions:Gut flora related to phosphorus metabolism in hemodialysis patients,and improving intestinal microbiota may regulate the absorption of phosphate in the intestine.The use of phosphate binder lanthanum carbonate leads to a tendency of decreasing microbial diversity and lower network complexity.展开更多
Background:Whether there is an association between serum uric acid(SUA)level and risk of mortality in the general population remains unclear.Based on the China National Survey of Chronic Kidney Disease linked to morta...Background:Whether there is an association between serum uric acid(SUA)level and risk of mortality in the general population remains unclear.Based on the China National Survey of Chronic Kidney Disease linked to mortality data,a population-based cohort study was performed to investigate the association between SUA level and all-cause mortality,cardiovascular disease(CVD)mortality,and cancer mortality in China.Methods:The survival status of participants in the cross-sectional survey was identified from January 1,2006 to December 31,2017.Only 33,268 individuals with complete SUA data among the 47,204 participants were included in the analysis.We determined the rates of all-cause mortality,CVD mortality,and cancer mortality.We used Cox proportional hazards regression models to evaluate the effect of the SUA level on mortality.Results:During a total of 297,538.4 person-years of follow-up,1282 deaths occurred.In the Cox proportional hazards regression model,the rate of all-cause mortality,CVD mortality,and cancer mortality had a U-shaped association with SUA levels only in men,whereas no significant associations were detected in women.For all-cause mortality in men,the multivariable-adjusted hazard ratios(HRs)in the first,second,and fourth quartiles compared with the third quartile were 1.31(95%confidence interval[CI]1.04–1.67),1.17(95%CI 0.92–1.47),and 1.55(95%CI 1.24–1.93),respectively.For CVD mortality,the corresponding HRs were 1.47(95%CI 1.00–2.18),1.17(95%CI 0.79–1.75),and 1.67(95%CI 1.16–2.43),respectively.For the cancer mortality rate,only a marginally significant association was detected in the fourth quartile compared with the third quartile with an HR of 1.43(95%CI 0.99–2.08).Conclusions:The association between SUA and mortality differed by sex.We demonstrated a U-shaped association with SUA levels for all-cause and CVD mortalities among men in China.展开更多
To the Editor:Minimal change disease(MCD)and focal segmental glomerulosclerosis(FSGS)are common histological subtypes of nephrotic syndrome in adults and children.^([1,2])Corticosteroids are the first-line treatment,w...To the Editor:Minimal change disease(MCD)and focal segmental glomerulosclerosis(FSGS)are common histological subtypes of nephrotic syndrome in adults and children.^([1,2])Corticosteroids are the first-line treatment,whereas some patients present with steroid-dependent nephrotic syndrome.Repeated treatment with steroids is required,accompanied by serious adverse effects related to prednisone monotherapy in the long term.展开更多
Background:Noncanonical autophagy is generally described as a lysosomal degradation process that requires only a subset of the core autophagy-related proteins to form functional autophagosomes.Review:Accumulating evid...Background:Noncanonical autophagy is generally described as a lysosomal degradation process that requires only a subset of the core autophagy-related proteins to form functional autophagosomes.Review:Accumulating evidence implicates noncanonical autophagy pathways in expanding the versatility of the immune system via regulation of functions that include antigen presentation,dead cell clearance,inflammatory cytokine production,and immune cell homeostasis.In this review,we use microtubuleassociated protein 1 light chain 3-associated phagocytosis(LAP)as an example of noncanonical autophagy,describing its distinctive molecular machinery and highlighting recent advances in its functioning in immunity.We also discuss the direct and indirect evidence supporting the pathogenic significance of abnormal levels of LAP in systemic lupus erythematosus(SLE).Future Perspectives:A better understanding of the role of noncanonical autophagy in SLE may reveal crucial information about the disease pathology,providing direction for therapeutic developments and improved prognosis.展开更多
基金Support was provided by the National Science Foundation of China(82022010,82131430172,81970613)the Beijing Natural Science Foundation(Z190023)+3 种基金Academy of Medical Sciences-Newton Advanced Fellowship(NAFR13\1033)the Fok Ying Tung Education Foundation(171030)the Beijing Nova Program Interdisciplinary Cooperation Project(Z191100001119004)the Chinese Academy of Medical Sciences Research Unit(2019RU023).
文摘Kidney disease is a leading cause of death worldwide.Currently,the diagnosis of kidney diseases and the grading of their severity are mainly based on clinical features,which do not reveal the underlying molecular pathways.More recent surge of∼omics studies has greatly catalyzed disease research.The advent of artificial intelligence(AI)has opened the avenue for the efficient integration and interpretation of big datasets for discovering clinically actionable knowledge.This review discusses how AI and multi-omics can be applied and integrated,to offer opportunities to develop novel diagnostic and therapeutic means in kidney diseases.The combination of new technology and novel analysis pipelines can lead to breakthroughs in expanding our understanding of disease pathogenesis,shedding new light on biomarkers and disease classification,as well as providing possibilities of precise treatment.
文摘Background Chronic kidney disease (CKD) is a common disorder associated with multiple adverse clinical consequences,especially cardiovascular risk and end-stage renal disease.A recent national survey demonstrated that CKD has become a leading health problem in China.There is an urgent need to implement an in-depth investigation of the CKD burden and also to explore underlying mechanisms of CKD progression and it association with adverse consequences.Methods The Chinese Cohort Study of Chronic Kidney Disease (C-STRIDE) is the first national CKD cohort in China.It will enroll approximately 3 000 pre-dialysis CKD patients aged between 18 and 74 years and follow-up for at least 5 years.Questionnaires,anthropometric measures,laboratory tests,and biomaterials will be collected at baseline and annually.The principal clinical outcomes of the C-STRIDE consist of renal disease events,cardiovascular events,and death.Based on the longitudinal clinical data and biomaterials,the risk factors with CKD progression and other outcomes will be analyzed,and candidate markers and predicted models will be established.Conclusion The C-STRIDE would provide important evidence for underlying mechanisms of CKD progression,valuable information for clinical guidelines,and healthcare policies in China.
文摘Background: Although that glomerulonephritis is the major cause of end-stage renal disease in developing countries such as China, the increasing prevalence of diabetes has contributed to the changing spectrum of predialysis chronic kidney disease. Recent studies have revealed an increased proportion of patients with diabetic kidney disease (DKD) in hemodialysis populations in large cities in China. However, studies regarding the clinical phenotype of DKD in China are extremely limited. The incidence, development, and prognosis of diabetic kidney disease (INDEED) study aims to investigate the incidence, progression, and prognosis of DKD, as well as the associated genetic, behavioral, and environmental factors and biomarkers in patients with DKD in China. Methods: INDEED study is a prospective cohort study based on all participants with diabetes in the Kailuan study, which is a general population-based cohort study in northern China. Altogether, over 10,000 participants with diabetes will be followed biennially. Questionnaires documenting general characteristics, behavioral and environmental factors, and medical history will be administrated. Anthropometric measurements and a series of laboratory tests will be peribrmed in one central laboratory. The DNA, plasma, and urine samples of every participant will be stored in a biobank for future research. Conclusions: INDEED study will provide essential information regarding the clinical phenotype and prognosis of patients with DKD in China and will be valuable to identity factors and biomarkers associated with patients with DKD in China.
基金the National Key Research and Development Program(Risk factors and pathogenesis of the development and progression of diabetic kidney disease,No.2016YFC1305405).
文摘For the past decades,the rapid growth of economy and transition of lifestyles have led to a rapid rise in the prevalence of diabetes in China.Due to the lack of standard process in prevention and management of diabetic kidney disease(DKD)in China,the Peking University Health Science Center organized experts in fields of nephrology and endocrinology to develop the Chinese consensus statement of DKD.This consensus emphasizes on evidence-based inquiry,and focuses on the following three topics:(1)risk factors of the incidence and progression of DKD;(2)the diagnosis of DKD and indication of renal biopsy;(3)the overall management of DKD.
基金National Natural Science Foundation of China(No.82090020,No.82090021,and No.82070748)the CAMS Innovation Fund for Medical Sciences(No.2019-I2M-5-046)the China International Medical Foundation-Renal Anemia Fund.
文摘To the Editor:Diabetic kidney disease(DKD)is the leading cause of the end-stage renal disease nowadays.[1]The etiology of DKD is complex and remains largely unknown.[2]A genome-wide association study showed that a common missense variant in COL4A3,rs55703767,played a protective role in DKD in type 1 diabetes mellitus in Europeans,and this effect depended on blood glucose levels.[3]However,data from type 2 diabetes mellitus(T2DM)are insufficient.
基金acknowledge National Natural Science Foundation of China(No.52072007,and No.82130021)National High Level Hospital Clinical Research Funding(High Quality Clinical Research Project of Peking University First Hospital,No.2022CR83)+4 种基金State Key Laboratory of Vascular Homeostasis and Remodeling at Peking University,National Key R&D Program of China(No.2022YFB3204400)Beijing Young Scientist Program(No.BJJWZYJH01201910001006)CAMS Innovation Fund for Medical Sciences(No.2019-I2M-5-046,and No.2020-JKCS-009)PKU-Baidu Fund(No.2020BD026,and No.2020BD044)Capital’s Funds for Health Improvement and Research(No.CFH2022-1-4071).
文摘The development of a wearable,easy-to-fabricate,and stable intelligent minisystem is highly desired for the closedloop management of diabetes.Conventional systems always suffer from large size,high cost,low stability,or complex fabrication.Here,we show for the first time a wearable,rapidly manufacturable,stability-enhancing microneedle patch for diabetes management.The patch consists of a graphene composite ink-printed sensor on hollow microneedles,a polyethylene glycol(PEG)-functionalized electroosmotic micropump integrated with the microneedles,and a printed circuit board for precise and intelligent control of the sensor and pump to detect interstitial glucose and deliver insulin through the hollow channels.Via synthesizing and printing the graphene composite ink,the sensor fabrication process is fast and the sensing electrodes are stable.The PEG functionalization enables the micropump a significantly higher stability in delivering insulin,extending its lifetime from days to weeks.The patch successfully demonstrated excellent blood glucose control in diabetic rats.This work may introduce a new paradigm for building new closedloop systems and shows great promise for widespread use in patients with diabetes.
基金This work was supported by grants from the Beijing Natural Science Foundation(No.7184253),and the National Natural Science Foundation of China(No.81800636).
文摘Background:High levels of plasma homocysteine occur almost uniformly in patients with end-stage renal disease(ESRD).IgA nephropathy(IgAN)is the most common form of primary glomerulonephritis and a common cause of ESRD in young adults.Here,we aimed to detect whether homocysteine was elevated and associated with clinical-pathologic manifestations of IgAN patients and tested its causal effects using a two-sample Mendelian randomization(MR)approach.Methods:For observational analysis,108 IgAN patients,30 lupus nephritis(LN)patients,50 minimal change disease(MCD)patients,and 206 healthy controls were recruited from April 2014 to April 2015.Their plasma homocysteine was measured and clinical-pathologic manifestations were collected from medical records.For MR analysis,we further included 1686 IgAN patients.The missense variant methylenetetrahydrofolate reductase C677T(rs1801133)was selected as an instrument,which was genotyped by TaqMan allele discrimination assays.Results:Majority of IgAN patients(93.52%,101/108)showed elevated levels of plasma homocysteine(>10μmol/L).Plasma homocysteine in IgAN patients was significantly higher than that in MCD patients(median:18.32 vs.11.15μmol/L,Z=-5.29,P<0.01)and in healthy controls(median:18.32 vs.10.00μmol/L,Z=-8.76,P<0.01),but comparable with those in LN patients(median:18.32 L vs.14.50μmol/L,Z=-1.32,P=0.19).Significant differences were observed in sub-groups of IgAN patients according to quartiles of plasma homocysteine for male ratio(22.22%vs.51.85%vs.70.37%vs.70.37%,χ2=14.29,P<0.01),serum creatinine(median:77.00 vs.100.00 vs.129.00 vs.150.00μmol/L,χ2=34.06,P<0.01),estimated glomerular filtration rate(median:100.52 vs.74.23 vs.52.68 vs.42.67 mL·min-1·1.73 m-2,χ2=21.75,P<0.01),systolic blood pressure(median:120.00 vs.120.00 vs.125.00 vs.130.00 mmHg,χ2=2.97,P=0.05),diastolic blood pressure(median 80.00 vs.75.00 vs.80.00 vs.81.00 mmHg,χ2=11.47,P<0.01),and pathologic tubular atrophy and interstitial fibrosis(T)(T0/T1/T2:62.96%/33.33%/3.70%vs.29.63%/40.74%/29.63%vs.24.00%/48.00%/28.00%vs.14.81%/37.04%/48.15%,χ2=17.66,P<0.01).The coefficient of each rs1801133-T allele on homocysteine levels after controlling age and sex was 7.12(P<0.01).MR estimates showed causal positive effects of homocysteine on serum creatine(β=0.76,P=0.02),systolic blood pressure(β=0.26,P=0.02),diastolic blood pressure(β=0.20,P=0.01),and pathologic T lesion(β=0.01,P=0.01)in IgAN.Conclusions:By observational and MR analyses,consistent results were observed for associations of plasma homocysteine with serum creatinine,blood pressures,and pathologic T lesion in IgAN patients.
基金the grants from the National Natural Science Foundation of China (No.81570664 and No.31671366) the National Key Research and Development Program of China (No.2017YFC 1200205).
文摘Background:Hyperphosphatemia is a risk factor associated with mortality in patients on maintenance hemodialysis.Gut absorption of phosphate is the major source.Recent studies indicated that the intestinal flora of uremic patients changed a lot compared with the healthy population,and phosphorus is an essential element of bacterial survival and reproduction.The purpose of this study was to explore the role of intestinal microbiota in phosphorus metabolism. Methods:A prospective self-control study was performed from October 2015 to January 2016.Microbial DNA was isolated from the stools of 20 healthy controls and 21 maintenance hemodialysis patients.Fourteen out of the 21 patients were treated with lanthanum carbonate for 12 weeks.Thus,stools were also collected before and after the treatment.The bacterial composition was analyzed based on 16S ribosomal RNA pyrosequencing.Bioinformatics tools,including sequence alignment,abundance profiling,and taxonomic diversity, were used in microbiome data analyses.Correlations between genera and the serum phosphorus were detected with Pearson's correlation. For visualization of the internal interactions and further measurement of the microbial community,SparCC was used to calculate the Spearman correlation coefficient with the corresponding P value between each two genera. Results:Thirteen genera closely correlated with serum phosphorus and the correlation coefficient was above 0.4(P <0.05).We also found that 58 bacterial operational taxonomic units (OTUs)were significantly different and more decreased OTUs were identified and seven genera (P <0.05)were obviously reduced after using the phosphate binder.Meanwhile,the microbial richness and diversity presented downward trend in hemodialysis patients compared with healthy controls and more downward trend after phosphorus reduction.The co-occurrence network of genera revealed that the network complexity of hemodialysis patients was significantly higher than that of controls,whereas treatment with lanthanum carbonate reduced the network complexity. Conclusions:Gut flora related to phosphorus metabolism in hemodialysis patients,and improving intestinal microbiota may regulate the absorption of phosphate in the intestine.The use of phosphate binder lanthanum carbonate leads to a tendency of decreasing microbial diversity and lower network complexity.
基金This study was supported by grants from the National Natural Science Foundation of China(Nos.91846101,81771938,81900665,82003529,82090021)Beijing Nova Programme Interdisciplinary Cooperation Project(No.Z191100001119008)+4 种基金National Key R&D Program of the Ministry of Science and Technology of China(No.2019YFC2005000)Chinese Scientific and Technical Innovation Project 2030(No.2018AAA0102100)the University of Michigan Health System-Peking University Health Science Center Joint Institute for Translational and Clinical Research(Nos.BMU2018JI012,BMU2019JI005)CAMS Innovation Fund for Medical Sciences(No.2019-I2M-5-046)PKU-Baidu Fund(No.2019BD017).
文摘Background:Whether there is an association between serum uric acid(SUA)level and risk of mortality in the general population remains unclear.Based on the China National Survey of Chronic Kidney Disease linked to mortality data,a population-based cohort study was performed to investigate the association between SUA level and all-cause mortality,cardiovascular disease(CVD)mortality,and cancer mortality in China.Methods:The survival status of participants in the cross-sectional survey was identified from January 1,2006 to December 31,2017.Only 33,268 individuals with complete SUA data among the 47,204 participants were included in the analysis.We determined the rates of all-cause mortality,CVD mortality,and cancer mortality.We used Cox proportional hazards regression models to evaluate the effect of the SUA level on mortality.Results:During a total of 297,538.4 person-years of follow-up,1282 deaths occurred.In the Cox proportional hazards regression model,the rate of all-cause mortality,CVD mortality,and cancer mortality had a U-shaped association with SUA levels only in men,whereas no significant associations were detected in women.For all-cause mortality in men,the multivariable-adjusted hazard ratios(HRs)in the first,second,and fourth quartiles compared with the third quartile were 1.31(95%confidence interval[CI]1.04–1.67),1.17(95%CI 0.92–1.47),and 1.55(95%CI 1.24–1.93),respectively.For CVD mortality,the corresponding HRs were 1.47(95%CI 1.00–2.18),1.17(95%CI 0.79–1.75),and 1.67(95%CI 1.16–2.43),respectively.For the cancer mortality rate,only a marginally significant association was detected in the fourth quartile compared with the third quartile with an HR of 1.43(95%CI 0.99–2.08).Conclusions:The association between SUA and mortality differed by sex.We demonstrated a U-shaped association with SUA levels for all-cause and CVD mortalities among men in China.
基金Natural Science Foundation of China(No.81870486,No.82070732)。
文摘To the Editor:Minimal change disease(MCD)and focal segmental glomerulosclerosis(FSGS)are common histological subtypes of nephrotic syndrome in adults and children.^([1,2])Corticosteroids are the first-line treatment,whereas some patients present with steroid-dependent nephrotic syndrome.Repeated treatment with steroids is required,accompanied by serious adverse effects related to prednisone monotherapy in the long term.
基金National Science Foundation of China,Grant/Award Numbers:82022010,8201101478,81970613,82000680Beijing Natural Science Foundation,Grant/Award Number:Z190023+2 种基金Fok Ying Tung Education Foundation,Grant/Award Number:171030Beijing Nova Program Interdisciplinary Cooperation Project,Grant/Award Number:Z191100001119004CAMS Innovation Fund for Medical Sciences,Grant/Award Number:2019-I2M-5-046。
文摘Background:Noncanonical autophagy is generally described as a lysosomal degradation process that requires only a subset of the core autophagy-related proteins to form functional autophagosomes.Review:Accumulating evidence implicates noncanonical autophagy pathways in expanding the versatility of the immune system via regulation of functions that include antigen presentation,dead cell clearance,inflammatory cytokine production,and immune cell homeostasis.In this review,we use microtubuleassociated protein 1 light chain 3-associated phagocytosis(LAP)as an example of noncanonical autophagy,describing its distinctive molecular machinery and highlighting recent advances in its functioning in immunity.We also discuss the direct and indirect evidence supporting the pathogenic significance of abnormal levels of LAP in systemic lupus erythematosus(SLE).Future Perspectives:A better understanding of the role of noncanonical autophagy in SLE may reveal crucial information about the disease pathology,providing direction for therapeutic developments and improved prognosis.