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Introduction: The new topical formula is urgent needed to meet clinical needs for majority mild patients with psoriasis. Deucravacitinib exerts outstanding anti-psoriatic capacity as an oral TYK2 inhibitor; however, single therapy is insufficient to target the complicated psoriatic skin, including excessive reactive oxygen species (ROS) and persistent inflammation. To address this need, engineered smart nano-therapeutics hold potential for the topical delivery of deucravacitinib. Methods: hydrophobic Deucravacitinib was loaded into polyethylene glycol block-polypropylene sulphide (PEG-b-PPS) for transdermal delivery in the treatment of psoriasis. The oxidative stress model of HaCaT psoriasis was established by TNF-α and IL-17A in vitro. JC-1 assay, DCFH-DA staining and mtDNA copy number were utilized to assess mitochondrial function. 0.75% Carbopol®934 was incorporated into SPMs to produce hydrogels and Rhb was labeled to monitor penetration by Immunofluorescence. In vivo, we established IMQ-induced psoriatic model to evaluate therapeutic effect of Car@Deu@PEPS. Results: Deu@PEPS exerted anti-psoriatic effects by restoring mitochondrial DNA copy number and mitochondrial membrane potential in HaCaT. In vivo, Car@Deu@PEPS supramolecular micelle hydrogels had longer retention time in the dermis in the IMQ-induced ROS microenvironment. Topical application of Car@Deu@PEPS significantly restored the normal epidermal architecture of psoriatic skin with abrogation of splenomegaly in the IMQ-induced psoriatic dermatitis model. Car@Deu@PEPS inhibited STAT3 signaling cascade with a corresponding decrease in the levels of the differentiation and proliferative markers Keratin 17 and Cyclin D1, respectively. Meanwhile, Car@Deu@PEPS alleviated IMQ-induced ROS generation and subsequent NLRP3 inflammasome-mediated pyroptosis. Conclusion: Deu@PEPS exerts prominent anti-inflammatory and anti-oxidative effects, which may offers a more patient-acceptable therapy with fewer adverse effects compared with oral deucravacitinib.
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Micelas , Mitocôndrias , Estresse Oxidativo , Psoríase , Espécies Reativas de Oxigênio , Espécies Reativas de Oxigênio/metabolismo , Psoríase/tratamento farmacológico , Psoríase/metabolismo , Humanos , Estresse Oxidativo/efeitos dos fármacos , Mitocôndrias/metabolismo , Mitocôndrias/efeitos dos fármacos , Animais , Camundongos , Pele/metabolismo , Pele/efeitos dos fármacos , Pele/patologia , Polímeros/química , Células HaCaT , Administração Cutânea , MasculinoRESUMO
BACKGROUND: Serine metabolism is crucial for tumour oncogenesis and immune responses. S-adenosyl methionine (SAM), a methyl donor, is typically derived from serine-driven one-carbon metabolism. However, the involvement of serine metabolism in psoriatic skin inflammation remains unclear. OBJECTIVES: To investigate the association between serine metabolism and psoriatic skin inflammation. METHODS: Clinical samples were collected from patients with psoriasis and the expression of serine biosynthesis enzymes was evaluated. The HaCaT human keratinocyte cell line was transfected with small interfering RNA (siRNA) of key enzyme or treated with inhibitors. RNA sequencing and DNA methylation assays were performed to elucidate the mechanisms underlying serine metabolism-regulated psoriatic keratinocyte inflammation. An imiquimod (IMQ)-induced psoriasis mouse model was established to determine the effect of the SAM administration on psoriatic skin inflammation. RESULTS: The expression of serine synthesis pathway enzymes, including the first rate-limiting enzyme in serine biosynthesis, phosphoglycerate dehydrogenase (PHGDH), was downregulated in the epidermal lesions of patients with psoriasis compared with that in healthy controls. Suppressing PHGDH in keratinocytes promoted the production of proinflammatory cytokines and enrichment of psoriatic-related signalling pathways, including the tumour necrosis factor-alpha (TNF-α) signalling pathway, interleukin (IL)-17 signalling pathway and NF-κB signalling pathway. In particular, PHGDH inhibition markedly promoted the secretion of IL-6 in keratinocytes with or without IL-17A, IL-22, IL-1α, oncostatin M and TNF-α (mix) stimulation. Mechanistically, PHGDH inhibition upregulated the expression of IL-6 by inhibiting SAM-dependent DNA methylation at the promoter and increasing the binding of myocyte enhancer factor 2A. Furthermore, PHGDH inhibition increased the secretion of IL-6 by increasing the activation of NF-κB via SAM inhibition. SAM treatment effectively alleviated IMQ-induced psoriasis-like skin inflammation in mice. CONCLUSIONS: Our study revealed the crucial role of PHGDH in antagonising psoriatic skin inflammation and indicated that targeting serine metabolism may represent a novel therapeutic strategy for treating psoriasis.
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Dermatite , Psoríase , Animais , Humanos , Camundongos , Dermatite/metabolismo , Modelos Animais de Doenças , Metilação de DNA , Imiquimode/uso terapêutico , Interleucina-6/metabolismo , Queratinócitos/metabolismo , Metionina , Camundongos Endogâmicos BALB C , NF-kappa B/metabolismo , NF-kappa B/farmacologia , NF-kappa B/uso terapêutico , Psoríase/patologia , Pele/patologia , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Current evidence suggests that IL-23, IL-6, and TNF-α play pivotal roles in the pathogenesis of psoriasis. Although it has been established that Sirtuin 3 (SIRT3) mediates the inflammatory process, the underlying mechanisms remain largely unclear. Herein, we substantiated that the inhibition or deletion of SIRT3 increased the acetylation level of spliced form of X-box binding protein 1 (XPB1s), enhancing its transcriptional activity and IL-23a production. Pharmacologically inhibition of XBP1s with MKC8866 downregulated the expression of inflammatory cytokines in SIRT3-inhibited or Sirt3-KO BMDMs stimulated by IMQ. Inhibition or knockdown of SIRT3 could exacerbate psoriasis-like skin inflammation in an imiquimod-induced psoriasis-like mouse model. Besides, a decrease in SIRT3 expression was observed in the macrophages of psoriasis patients, which increased the expression and acetylation level of XBP1s. Overall, we provide compelling evidence of the crucial role of SIRT3 in the IL-23 axis in psoriatic inflammation and novel molecular insights into the anti-inflammatory effects of SIRT3.
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Dermatite , Psoríase , Sirtuína 3 , Animais , Camundongos , Imiquimode/efeitos adversos , Inflamação , Interleucina-23/metabolismo , Macrófagos/metabolismo , Psoríase/induzido quimicamente , Psoríase/tratamento farmacológico , Psoríase/metabolismo , Sirtuína 3/metabolismo , Receptor 7 Toll-Like/metabolismo , Proteína 1 de Ligação a X-Box/genéticaRESUMO
BACKGROUND: Little is known about mortality trends among patients with psoriasis (PsO) and psoriatic arthritis (PsA) in the United States. OBJECTIVES: To ascertain mortality trends of PsO and PsA between 2010 and 2021, focusing on the effects of the COVID-19 pandemic. METHODS: We collected data from the National Vital Statistic System and calculated age-standardized mortality rates (ASMR) and cause-specific mortality for PsO/PsA. We evaluated observed versus predicted mortality for 2020-2021 based on trends from 2010 to 2019 with joinpoint and prediction modelling analysis. RESULTS: Among 5810 and 2150 PsO- and PsA-related deaths between 2010 and 2021, ASMR for PsO dramatically increased between 2010-2019 and 2020-2021 (annual percentage change [APC] 2.07% vs. 15.26%; p < 0.01), leading to a higher observed ASMR (per 100,000 persons) than predicted for 2020 (0.27 vs. 0.22) and 2021 (0.31 vs. 0.23). The excess mortality of PsO was 22.7% and 34.8% higher than that in the general population in 2020 (16.4%, 95% CI: 14.9%-17.9%) and 2021 (19.8%, 95% CI: 18.0%-21.6%) respectively. Notably, the ASMR rise for PsO was most pronounced in the female (APC: 26.86% vs. 12.19% in males) and the middle-aged group (APC: 17.67% vs. 12.47% in the old-age group). ASMR, APC and excess mortality for PsA were similar to PsO. SARS-CoV-2 infection contributed to more than 60% of the excess mortality for PsO and PsA. CONCLUSIONS: Individuals living with PsO and PsA were disproportionately affected during the COVID-19 pandemic. Both ASMRs increased at an alarming rate, with the most pronounced disparities among the female and middle-aged groups.
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Artrite Psoriásica , COVID-19 , Psoríase , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Artrite Psoriásica/mortalidade , COVID-19/epidemiologia , Pandemias , Psoríase/mortalidade , SARS-CoV-2 , Estados Unidos/epidemiologiaRESUMO
Vaccination is the primary defense against severe acute respiratory syndrome coronavirus 2, especially among older adults and those with chronic conditions. Using a nationally representative sample of 12,900 participants from the fifth wave (2021-2022) of the China Health and Retirement Longitudinal Study (CHARLS), we examined the coronavirus disease 2019 (COVID-19) vaccination status and the determinants of vaccination hesitancy in Chinese adults aged 52 and older. By July/August 2022, 92.3% of the Chinese population aged 60 years and older had received at least one COVID-19 vaccination, 88.6% had completed the primary series and 72.4% had received a booster. Those aged 80 years and older had lower vaccination rates, with 71.9% and 46.7% completing the primary series and booster shots, respectively. These statistics represent the situation before China ended the Zero-COVID policy in November 2022 because vaccination stagnated between July/August and November 2022. Multivariate regression analysis revealed that belonging to the oldest age groups (individuals aged 70 years and older and especially those aged 80 years and older) as well as being female and unmarried, residing in urban areas, being functionally dependent and having chronic conditions meant that these individuals were less likely to receive COVID-19 vaccines. Our regression analysis results were corroborated by self-reported reasons for nonvaccination. Vaccination hesitancy probably contributed to excessive mortality among vulnerable populations after China ceased its Zero-COVID policy. Our study provides important lessons on how to balance containment efforts with vaccination and treatment measures, as well as highlighting the need to clarify the side effects and contraindications of vaccines early on.
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COVID-19 , Humanos , Feminino , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Masculino , COVID-19/epidemiologia , COVID-19/prevenção & controle , Vacinas contra COVID-19/uso terapêutico , Estudos Longitudinais , SARS-CoV-2 , China/epidemiologia , VacinaçãoRESUMO
Although the anti-inflammatory effect of serum- and glucocorticoid-regulated protein kinase 1 (SGK1) has been established in other diseases, the possible regulatory role of SGK1 in psoriasis and the underlying molecular mechanisms remain largely unknown. In this study, we found that SGK1 expression was decreased in macrophages from patients with psoriasis. Moreover, a specific pharmacological SGK1 inhibitor, EMD638683, significantly enhanced imiquimod-mediated toll-like receptor 7/8 activity and proinflammatory cytokine production in RAW264.7 cells, and this result was confirmed by Sgk1 small interfering RNA. Further mechanistic data showed that SGK1 inhibition increased the phosphorylation of Bruton's agammaglobulinemia tyrosine kinase; moreover, Bruton's agammaglobulinemia tyrosine kinase inhibition abrogated the proinflammatory effects of the SGK1 inhibitor on toll-like receptor 7/8 activation, thereby validating that SGK1 inhibition enhances the toll-like receptor 7/8 pathway by increasing Bruton's agammaglobulinemia tyrosine kinase phosphorylation. In addition, our in vivo results showed that SGK1 inhibition significantly increased the secretion of proinflammatory cytokines, including IL-1ß, IL-6, and TNF-α, and the infiltration of T helper 17 cells in an imiquimod-induced psoriasis mouse model. Altogether, these results show that SGK1 plays a critical role in the pathogenesis of psoriasis by modulating inflammatory responses in skin lesions, indicating that SGK1âBruton's agammaglobulinemia tyrosine kinase signaling could be a novel therapeutic target for the control of psoriasis.
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Dermatite , Psoríase , Camundongos , Animais , NF-kappa B/metabolismo , Citocinas/metabolismo , Imiquimode/uso terapêutico , Receptor 7 Toll-Like , Proteínas Quinases , Glucocorticoides/uso terapêutico , Psoríase/induzido quimicamente , Psoríase/tratamento farmacológico , Psoríase/patologiaRESUMO
BACKGROUND: Psoriasis is an immune-mediated skin disorder caused by the proliferation of keratinocytes. Although psoriasis is generally diagnosed based on clinical manifestations, sensitive biomarkers are needed to help diagnose psoriasis early with atypical presentations. MicroRNAs play a functional role in the development of psoriasis, and they are stable and suitable as biomarkers in psoriasis. MATERIAL AND METHODS: The GSE50790 and GSE53552 datasets from the Gene Expression Omnibus (GEO) database were used to identify Differentially Expressed Genes (DEGs) between the control group and the lesional group. DEGs were processed for enrichment analysis to explore the functions, and a Protein-Protein Interaction (PPI) network was constructed to obtain gene clusters. The signalling pathway associated with gene cluster 1 was processed to further identify related genes. Hub genes were obtained through the intersection of cluster 1 and the related genes. Hub genes were used to predict the miRNAs through a gene-miRNA interaction network. The relative expression of miRNAs was measured by qRT-PCR to identify the suitability of miRNAs as biomarkers. RESULTS: Bioinformatics analysis revealed that the chemokine signalling pathway is involved in the development of psoriasis. Five related miRNAs were mined from the datasets, and qRT-PCR showed that hsa-miR-612 (p=0.0015), hsa-miR-3194-5p (p=0.0078) and hsa-miR-4316 (p<0.0001) may be potential biomarkers in psoriasis.
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MicroRNAs , Psoríase , Humanos , Perfilação da Expressão Gênica , MicroRNAs/genética , MicroRNAs/metabolismo , Biomarcadores , Redes Reguladoras de Genes , Psoríase/diagnóstico , Psoríase/genética , Biologia ComputacionalRESUMO
BACKGROUND: An ageing population coupled with an increase in morbidity places a considerable burden on health and social care systems. The aim of our study was to estimate the trends in functional dependency and project future care needs for older people in China. METHODS: We analysed data from the China Health and Retirement Longitudinal Study, a nationally representative survey of a cohort of Chinese people (aged ≥45 years) from 150 counties or districts and 450 villages or urban communities across 28 provinces, who were selected by use of multistage stratified probability-proportionate-to-size sampling. The baseline survey was conducted in 2011 and follow-up surveys were conducted in 2013, 2015, 2018, and 2020. We excluded people younger than 60 years or people who had missing variables on dependency in the five follow-up interviews. Three dependency levels were determined on the basis of activities of daily living (ADLs) and instrumental activities of daily living (IADLs): any ADL items (level 1 dependency); any ADL items or difficulty cooking, shopping, or taking medications (level 2 dependency); and difficulty in any ADL or IADL items (level 3 dependency). The dependency rates were extrapolated to derive the number of people older than 60 years with dependency in China from 2011 to 2020. We used a regression model to project future changes and forecast the size of the older population with dependency between 2021 and 2030. FINDINGS: A total of 89 031 individuals across five waves completed the surveys, of whom 46 619 were eligible for inclusion. The prevalence of level 1 dependency among older Chinese adults declined from 11·7% (95% CI 10·6-12·8) in 2011 to 8·1% (7·5-8·7) in 2020. Level 2 and level 3 dependency also declined. The total number of older people requiring care in 2020 was 20·61 million (95% CI 19·01-22·20) with level 1 dependency, 36·33 million (34·27-38·40) with level 2 dependency, and 45·30 million (43·02-47·59) with level 3 dependency. Improved education, housing, and access to health care was associated with 41·84% of the decline in level 3 dependency prevalence between 2011 and 2020. By 2030, the projected dependency rates could decline to 8·04% for level 1 dependency, 13·28% for level 2 dependency, and 16·05% for level 3 dependency. Nonetheless, the cohort size will grow, resulting in more older Chinese people who need care (29·71 million [27·07-32·36] in level 1, 49·07 million [45·98-52·16] in level 2, and 59·32 million [55·94-62·70] in level 3) in 2030. By 2030, we estimate that 14·02 million more older Chinese people will need care than in 2020. INTERPRETATION: Rapid ageing of the population could offset the decline in dependency and result in a substantial increase in the population with complex care needs. Promoting healthy ageing and investing in an age-friendly environment are important in reducing care burdens in China. FUNDING: National Institute on Aging, Natural Science Foundation of China, China Medical Board. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.
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Atividades Cotidianas , Aposentadoria , Adulto , Humanos , Pessoa de Meia-Idade , Idoso , Estudos Longitudinais , Envelhecimento , China/epidemiologiaRESUMO
BACKGROUND: Psoriasis is associated with an increased risk for cardiovascular disease (CVD). Methotrexate (MTX) is often used as a first-line system therapy and there is a need to determine its effect on whole blood viscosity (WBV) and plasma viscosity (PV) in psoriasis.METHODSA prospective, single-center, interventional study with a total of 111 psoriatic patients who received MTX therapy from October 22, 2018, to December 28, 2019, and 111 age- and sex-matched healthy controls. Changes in WBV, PV, blood counts, liver and renal function were evaluated.RESULTSPsoriatic patients had significantly higher levels of WBV and relative viscosity (RV) at low shear rate (LSR), erythrocyte aggregation index (EAI), and PV than sex and age-matched healthy controls. PV was positively correlated with erythrocyte sedimentation rate (ESR), ESR was positively correlated with high sensitive C-reactive protein (hCRP). But only hCRP was positively associated with psoriasis area severity index (PASI) score. MTX significantly decreased the levels of PV, ESR, hCRP, and blood pressure (BP) in male patients, and the level of WBV in female patients. CONCLUSION: Sex-specific downregulation of MTX on WBV, PV, hCRP, and BP, indicating that the effect of MTX on the risk of cardiovascular disease was related with sex.
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Doenças Cardiovasculares , Psoríase , Viscosidade Sanguínea/fisiologia , Regulação para Baixo , Feminino , Humanos , Masculino , Metotrexato/uso terapêutico , Estudos Prospectivos , Psoríase/tratamento farmacológico , ViscosidadeRESUMO
China has a lower rate of vaccination among older adults and those who have chronic conditions and functional disabilities. As China has recently ended the zero-COVID policy, understanding the factors behind low vaccination rates among these vulnerable populations can inform immediate policy priorities to save lives for China and offer lessons for the world at large. We used the fifth wave (2021-22) of the China Health and Retirement Longitudinal Study (CHARLS), which represented mainland Chinese 45 and older. Vaccination status was updated in the summer of 2022, reflecting the current situation because very few additional vaccinations were administered afterward. For those who were unvaccinated, self-reported reasons were recorded. Using regression analysis, we investigated the determinants of non-vaccination, including demographics, functional status, and chronic conditions. In addition, two-thirds of the respondents had their vaccination status recorded twice in 2021 and 2022, allowing us to examine changes in vaccination rates in the recent year, zeroing in on the effects of the government's most recent vaccination campaign. Finally, we corroborated the regression results using self-reported reasons for non-vaccination in both years. A total of 12900 participants were included in the analysis. By the summer of 2022, the weighted COVID-19 vaccination rate among older Chinese people (≥60 years old) was 92.3%, with 88.8% having completed the primary series and 72.7% having received boosters. Only 72.0% of the oldest-old (≥80 years old) had completed the primary series, and 47.1% had had boosters. Regression analysis showed that participants who were older, female, unmarried, registered with urban Hukou residence, functionally dependent, and comorbid with chronic conditions were less likely to receive COVID-19 vaccines. A significant increase in vaccination rates among ethnic minorities, older adults, rural residents, and those with chronic conditions and functional dependency was observed in the year after the winter of 2021 when the government started to push for universal vaccination. The self-reported reasons for non-vaccination in 2022 were contraindications (48%), advanced ages/frailty/health conditions (21%), problems in accessing vaccines (18%), concerns about side effects or efficacy (9%), and having never heard of COVID-19 vaccine (6%). Nevertheless, as China has ended the zero-COVID policy, many older people, especially the oldest and those with chronic conditions and disabilities, have not yet been fully vaccinated with the primary series or booster doses, exposing them to the danger of infection. Therefore, health authorities should immediately abandon the previous practice of refusing to vaccinate those with chronic conditions, change people's mistaken perceptions of contraindications and side effects, and improve access to vaccines. Most importantly, China should strengthen public trust in vaccines by making information transparent regarding the vaccine's protection rates and side effects.
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BACKGROUND: Association between blood pressure (BP) and kidney function among the middle and old aged general population without hypertension remains unclear. METHODS: Participants aged ≥ 45 years, with complete data in 2011 and 2015 interviews of the China Health and Retirement Longitudinal Study(CHARLS), and without pre-existing hypertension were included. Systolic BP (SBP) was categorized as low (< 120 mmHg), medium (120-129 mmHg), and high (120-139 mmHg). Diastolic BP (DBP) was categorized as low (< 60 mmHg), medium (60-74 mmHg), and high (75-89 mmHg). Pulse pressure (PP) was categorized as normal (< 60 mmHg) and high (≥ 60 mmHg). The outcome was defined as rapid decline of estimated glomerular filtration rate(eGFR, decline ≥ 4 ml/min/1.73 m2/year). BP combination was designed according to the category of SBP and PP. The association between BP components, types of BP combination, and the risk of rapid decline of eGFR was analyzed using multivariate logistic regression models, respectively. Age-stratified analyses were conducted. RESULTS: Of 4,534 participants included, 695(15.3%) individuals were recognized as having rapid decline of eGFR. High PP[odds ratio(OR) = 1.34, 95%confidence interval(CI) 1.02-1.75], low SBP (OR = 1.28, 95%CI 1.03-1.59), and high SBP (OR = 1.32, 95% CI 1.02-1.71) were significantly associated with the risk of eGFR decline. Low SBP were associated with 65% increment of the risk of eGFR decline among participants aged < 55 years. The combination of high SBP and high PP (OR = 1.79, 95% CI 1.27-2.54) and the combination of low SBP and high PP (OR = 3.07, 95% CI 1.24-7.58) were associated with the increased risk of eGFR decline among the middle and old aged general population. CONCLUSION: Single and combination of high PP and high SBP could be the risk indicators of eGFR decline among the middle and old aged general population.
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Hipertensão , Insuficiência Renal Crônica , Idoso , Pressão Sanguínea/fisiologia , China/epidemiologia , Humanos , Rim , Estudos Longitudinais , Pessoa de Meia-Idade , Insuficiência Renal Crônica/etiologia , AposentadoriaRESUMO
There is growing evidence that microRNA-148b (miR-148b) can inhibit the growth of malignant cells while sirtuin 7 (SIRT7) may perform its carcinogenic effect by deacetylating H3K18. This study investigated the mechanism of miR-148b/SIRT7 on how it affects the malignant biological behavior of melanoma. It was established that the expression of miR-148b was downregulated in melanoma while that of SIRT7 was upregulated but negatively regulated by miR-148b through binding to the 3'UTR of SIRT7. Ectopic expression of miR-148b reduced the proliferation, migration, and invasion of melanoma cells, but SIRT7 reversed these functions of miR-148b. Moreover, tumor growth and metastasis experiments showed that miR-148b could significantly suppress proliferation and metastasis of melanoma in vivo. Overall, miR-148b inhibits the malignant biological behavior of melanoma by reducing the expression level of SIRT7. The development of miR-148b as a novel potential therapeutic approach for melanoma may be possible in the future.
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Regulação Neoplásica da Expressão Gênica , Melanoma/genética , MicroRNAs/metabolismo , Sirtuínas/genética , Neoplasias Cutâneas/genética , Regiões 3' não Traduzidas/genética , Animais , Sequência de Bases , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Regulação para Baixo/genética , Humanos , Melanoma/patologia , Camundongos Nus , MicroRNAs/genética , Invasividade Neoplásica , Metástase Neoplásica , Sirtuínas/metabolismo , Neoplasias Cutâneas/patologia , Regulação para Cima/genéticaRESUMO
Objective: Increased cancer risk after dialysis or transplantation has been recognized, but studies of cancer in pre-dialysis chronic kidney disease (CKD) are extremely limited. Therefore, we aim to investigate the risk of cancer in individuals with reduced kidney function. Methods: This study was based on China Health and Retirement Longitudinal Study (CHARLS), a nationally representative population aged ≥ 45 years old. We included 11 508 (5364 male) individuals with measurement of serum creatinine and without history of cancer at baseline. Incident cancer cases were documented in the biennial questionnaire. Results: The mean age was 58.7 ± 9.8 years. Participants with estimated glomerular filtration rate (eGFR) ≥ 90 ml/min/1.73m2, 60 to 89 ml/min/1.73m2, and eGFR < 60 ml/min/1.73m2 accounted for 62.9%, 33.7% and 3.4%, respectively. During 42 895 person-years' follow-up, 217 new cases of cancer were recorded. In participants with eGFR < 90 ml/min/1.73m2, cubic spline showed linear relationship between the risk of cancer and eGFR, while remained stable and no association in participants with eGFR > 90 ml/min/1.73m2. Compared to participants with eGFR ≥ 90 ml/min/1.73m2, those with eGFR < 60 ml/min/1.73m2 was associated with the increased risk of cancer in the fully adjusted model (hazard ratio 2.08; 95% confidence interval 1.22-3.53); and the risk for kidney and lung cancers was higher among those with eGFR < 60 ml/min/1.73m2. Conclusion: Reduced kidney function is associated with a higher risk of cancer and should be integrated into risk-stratification of cancer screening and management.
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Chronic kidney disease (CKD) is a public health burden, and anemia is common among patients with CKD. However, less is known regarding the longitudinal association between anemia and deterioration of kidney function among the general population. The China Health and Retirement Longitudinal Study is a nationally representative survey for households with members aged ≥ 45 years. Participants without creatinine and demographic data in 2011 and 2015 were excluded. Anemia was defined according to definitions of the World Health Organization. Rapid decline in kidney function was defined as a ≥16.9% (quartile 3) decline in estimated glomerular filtration rate (eGFR), calculated using the CKD-EPI equation during 2011-2015. Multivariate logistic regression and restricted cubic splines were used to explore their relationship. Altogether, 7210 eligible participants were included in the analysis, with a mean age of 58.6 ± 8.8 years. Rapid decline in kidney function occurred among 1802 (25.0%) participants. Those with kidney function decline were more likely to be older, male, and have anemia, lower eGFRs, hypertension, and cardiovascular disease (P < 0.05). Anemia, or hemoglobin, was independently associated with rapid decline in kidney function after adjusting for potential confounding factors (OR = 1.64, 95% CI, 1.32-2.04; OR = 0.90, 95% CI, 0.87-0.94, respectively). Restricted cubic splines showed a nonlinear relationship between hemoglobin and rapid decline in kidney function, especially for men with anemia (P < 0.05). In conclusion, anemia is an independent risk factor for progression of kidney function among the middle-aged and elderly population. Attentive management and intervention strategies targeting anemia could be effective to reduce the risk of kidney failure and improve the prognosis of the general population.
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Anemia/epidemiologia , Rim/patologia , Insuficiência Renal Crônica/epidemiologia , Anemia/metabolismo , Anemia/patologia , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/metabolismo , Doenças Cardiovasculares/patologia , China/epidemiologia , Creatinina/metabolismo , Progressão da Doença , Feminino , Taxa de Filtração Glomerular/fisiologia , Humanos , Hipertensão/epidemiologia , Hipertensão/metabolismo , Hipertensão/patologia , Rim/metabolismo , Testes de Função Renal/métodos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Prognóstico , Insuficiência Renal/epidemiologia , Insuficiência Renal/metabolismo , Insuficiência Renal/patologia , Insuficiência Renal Crônica/metabolismo , Insuficiência Renal Crônica/patologia , Fatores de RiscoRESUMO
BACKGROUND: The relationship between kidney function and hearing loss has long been recognized, but evidence of this association mostly comes from small observational studies or other populations. The aim of this study is to explore the association between reduced kidney function and hearing loss in a large population-based study among the middle-aged and elderly Chinese. METHODS: Data collected from the Chinese Health and Retirement Longitudinal Study (CHARLS) in 2015 were used for analysis. A cross-sectional study was conducted among 12,508 participants aged 45 years and older. Hearing loss, the outcome of this study, was defined according to interviewees' responses to three survey questions related to hearing in the CHARLS. Estimated glomerular filtration rate (eGFR) was employed to assess kidney function, and participants were classified into three categories based on eGFR: ≥90, 60-89 and < 60 mL/min/1.73 m2. Multivariable logistic regression was employed to adjust for potential confounders, including demographics, health-related behaviors, and cardiovascular risk factors. RESULTS: The overall prevalence of self-reported hearing loss in the study population was 23.6%. Compared with participants with eGFR ≥90 mL/min/1.73 m2, participants with eGFR of 60-89 mL/min/1.73 m2 (odds ratio [OR]: 1.11, 95% confidence interval [CI]: 1.00-1.23) and eGFR < 60 mL/min/1.73 m2 (OR: 1.25, 95% CI: 1.04-1.49) showed increased risk of hearing loss after adjusting for potential confounders. CONCLUSIONS: Reduced kidney function is independently associated with hearing loss. Testing for hearing should be included in the integrated management of patients with chronic kidney disease.
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Perda Auditiva , Insuficiência Renal Crônica , China/epidemiologia , Correlação de Dados , Estudos Transversais , Feminino , Taxa de Filtração Glomerular , Perda Auditiva/diagnóstico , Perda Auditiva/epidemiologia , Perda Auditiva/etiologia , Testes Auditivos/métodos , Humanos , Testes de Função Renal/métodos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Prevalência , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/epidemiologia , Insuficiência Renal Crônica/fisiopatologia , Fatores de RiscoRESUMO
Blood biomarkers provide critical information about the health of older populations, especially in large developing countries where self-reports of health are often inaccurate due to lack of access to health care. However, it is very difficult to collect blood samples in representative population surveys in such countries. The China Health and Retirement Longitudinal Study (CHARLS), a nationally representative study of middle-aged and older Chinese, represents one of the first efforts to include blood biomarkers in a nationally representative survey of China. In the 2015 wave of CHARLS, 13,013 respondents located in 150 counties around China donated whole blood, which was assayed on a range of indicators. Here we describe the process of the sample collection, transportation, storage, and analysis and present basic statistics.