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BACKGROUND: IgA nephropathy is an important global cause of kidney failure. Dysregulation of IgA production is thought to play a key role in IgA nephropathy pathogenesis, however, little is known about the epigenetic mechanisms such as RNA 5- methylcytosine (5mC) modification in regulating IgA synthesis. METHODS: To decipher the role of RNA 5mC in regulation of IgA class switch, the miR-23b-/- and LCWE induced Kawasaki disease mice were treated with 5-azacytidine. Trdmt1-/- and double Trdmt1-/-/ miR-23b-/- mice, Aid-/- mice or Aid-/-/ miR-23b-/- mice were also employed. RESULTS: We showed that miR-23b down regulated expression of Transfer RNA Aspartic Acid Methyltransferase 1 (Trdmt1) and consequently reduced 5-methylcytosine (m5C) RNA modification and IgA synthesis in B cells. Inhibition of m5C RNA modification normalised serum IgA levels and ameliorated progression of the IgA nephropathy-like kidney disease in miR-23b-/- and Kawasaki disease mice while mesangial IgA and C3 deposition failed to develop in Trdmt1-/-miR-23b-/- mice. By contrast, increased m5C RNA modification resulted in an exaggerated IgA nephropathy phenotype. miR-23b regulation of serum IgA levels and the development of an IgA nephropathy-like kidney disease in miR-23b-/- and Kawasaki disease mice is likely mediated through TRDMT1 driven 5-methylcytosine RNA modification in B cells, resulting in impaired activation-induced cytidine deaminase activity and IgA class switch recombination. CONCLUSIONS: This study revealed TRDMT1 induced RNA 5mC methylation regulate IgA class switch and inhibition of RNA 5mC by 5-Azacytidine could ameliorate progression of IgA nephropathy.
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BACKGROUND: High-frequency repeated transcranial magnetic stimulation (rTMS) stimulating the primary motor cortex (M1) is an alternative, adjunctive therapy for improving the motor symptoms of Parkinson's disease (PD). However, whether the high frequency of rTMS positively correlates to the improvement of motor symptoms of PD is still undecided. By controlling for other parameters, a disease animal model may be useful to compare the neuroprotective effects of different high frequencies of rTMS. OBJECTIVE: The current exploratory study was designed to compare the protective effects of four common high frequencies of rTMS (5, 10, 15, and 20 Hz) and iTBS (a special form of high-frequency rTMS) and explore the optimal high-frequency rTMS on an animal PD model. METHODS: Following high frequencies of rTMS application (twice a week for 5 weeks) in a MPTP/probenecid-induced chronic PD model, the effects of the five protocols on motor behavior as well as dopaminergic neuron degeneration levels were identified. The underlying molecular mechanisms were further explored. RESULTS: We found that all the high frequencies of rTMS had protective effects on the motor functions of PD models to varying degrees. Among them, the 10, 15, and 20 Hz rTMS interventions induced comparable preservation of motor function through the protection of nigrostriatal dopamine neurons. The enhancement of brain-derived neurotrophic factor (BDNF), dopamine transporter (DAT), and vesicular monoamine transporter 2 (VMAT-2) and the suppression of TNF-α and IL-1ß in the nigrostriatum were involved in the process. The efficacy of iTBS was inferior to that of the above three protocols. The effect of 5 Hz rTMS protocol was weakest. CONCLUSIONS: Combined with the results of the present study and the possible side effects induced by rTMS, we concluded that 10 Hz might be the optimal stimulation frequency for preserving the motor functions of PD models using rTMS treatment.
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Modelos Animales de Enfermedad , Ratones Endogámicos C57BL , Trastornos Parkinsonianos , Probenecid , Estimulación Magnética Transcraneal , Animales , Estimulación Magnética Transcraneal/métodos , Ratones , Masculino , Probenecid/farmacología , Trastornos Parkinsonianos/inducido químicamente , Trastornos Parkinsonianos/terapia , Trastornos Parkinsonianos/metabolismo , Trastornos Parkinsonianos/fisiopatología , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Corteza Motora/metabolismo , Corteza Motora/fisiopatología , Neuronas Dopaminérgicas/metabolismo , Proteínas de Transporte de Dopamina a través de la Membrana Plasmática/metabolismo , Interleucina-1beta/metabolismo , Sustancia Negra/metabolismo , Cuerpo Estriado/metabolismo , Proteínas de Transporte Vesicular de Monoaminas/metabolismo , Intoxicación por MPTP/terapia , Intoxicación por MPTP/prevención & control , Intoxicación por MPTP/metabolismo , Intoxicación por MPTP/fisiopatología , Actividad Motora/fisiología , 1-Metil-4-fenil-1,2,3,6-Tetrahidropiridina/farmacologíaRESUMEN
The white adipose tissue-specific aptamer Adipo8 can specificity bindwith mature adipocytes or tissues and inhibit adipogenesis.In this research, we exploredthe effect of Adipo8 intervention on the transcriptome in the process of adipogenesis using mRNA-level sequencing,analyzed the mechanism ofAdipo8 ininhibiting adipogenesis. The results showed that Adipo8 can inhibit lipid formation and downregulate PPARγ and C/EBPα in differentiated 3 T3-L1 cells. Transcriptome mRNA sequencing of 3 T3-L1 cells after Adipo8 interventionrevealed that Adipo8 might inhibit the biological function of adipogenesis by downregulating Acsl1 and Plin1 to inhibit fatty acid metabolism and PPAR signaling pathways.After that, using Spacer18 to connect the optimized and truncated Adipo8, we constructed a bivalent aptamer Adipo8cBand compared the affinity, biological effects, and biological stability between the aptamers in differentiated and mature 3 T3-L1 cells. At the cellular level,the affinity, biological effects, and serum stability of Adipo8cB were verified to be superior to those of Adipo8in 3 T3-L1 cells.We then investigated the biological properties of Adipo8cB as a lipid-inhibiting drug invivo, using C57BL/6J mice with diet-induced obesity. The body weight, blood sugar, lipid levels, liver function, glucose tolerance, and other related indicators in each group of mice were observed and compared after intervention with the bivalent aptamers Adipo8cB and Adipo8. Both Adipo8cB and Adipo8 effectively prevented weight gain caused by fat accumulation in micewith diet induced obesity, while also reducing blood lipid levels, improving glucose tolerance, and protecting against liver steatosis, moreover, Adipo8cB has a better effect than Adipo8.
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Células 3T3-L1 , Tejido Adiposo Blanco , Aptámeros de Nucleótidos , Ratones Endogámicos C57BL , Obesidad , Animales , Ratones , Obesidad/metabolismo , Tejido Adiposo Blanco/metabolismo , Tejido Adiposo Blanco/efectos de los fármacos , Aptámeros de Nucleótidos/farmacología , Masculino , Adipogénesis/efectos de los fármacos , Adipogénesis/fisiología , Dieta Alta en Grasa/efectos adversosRESUMEN
Rationale & Objective: The Kidney Failure Risk Equations have been proven to perform well in multinational databases, whereas validation in Asian populations is lacking. This study sought to externally validate the equations in a community-based chronic kidney disease cohort in China. Study Design: A retrospective cohort study. Setting & Participants: Patients with and estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2 dwelling in an industrialized coastal city of China. Exposure: Age, sex, eGFR, and albuminuria were included in the 4-variable model, whereas serum calcium, phosphate, bicarbonate, and albumin levels were added to the previously noted variables in the 8-variable model. Outcome: Initiation of long-term dialysis treatment. Analytical Approach: Model discrimination, calibration, and clinical utility were evaluated by Harrell's C statistic, calibration plots, and decision curve analysis, respectively. Results: A total of 4,587 participants were enrolled for validation of the 4-variable model, whereas 1,414 were enrolled for the 8-variable model. The median times of follow-up were 4.0 (interquartile range: 2.6-6.3) years for the 4-variable model and 3.4 (2.2-5.6) years for the 8-variable model. For the 4-variable model, the C statistics were 0.750 (95% CI: 0.615-0.885) for the 2-year model and 0.766 (0.625-0.907) for the 5-year model, whereas the values were 0.756 (0.629-0.883) and 0.774 (0.641-0.907), respectively, for the 8-variable model. Calibration was acceptable for both the 4-variable and 8-variable models. Decision curve analysis for the models at the 5-year scale performed better throughout different net benefit thresholds than the eGFR-based (<30 mL/min/1.73 m2) strategy. Limitations: A large proportion of patients lack albuminuria measurements, and only a subset of population could provide complete data for the 8-variable equation. Conclusions: The kidney failure risk equations showed acceptable discrimination and calibration and better clinical utility than the eGFR-based strategy for incidence of kidney failure among community-based urban Chinese patients with chronic kidney disease.
Accurate and reliable risk evaluation of chronic kidney disease (CKD) prognosis can be helpful for physicians to make decisions concerning treatment opportunity and therapeutic strategy. The kidney failure risk equation is an outstanding model for predicting risk of kidney failure among patients with CKD. However, the equation is lacking validation among Chinese populations. In the current study, we demonstrated that the equation had good discrimination among an urban community-based cohort of patients with CKD in China. The calibration was also acceptable. Decision curve analysis also showed that the equation performed better than a traditional kidney function-based strategy. The results provide the basis for using predictions derived from the kidney failure risk equation to improve the management of patients with CKD in community settings in China.
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The increasing frequency of heat waves under the global urbanization and climate change background poses elevating risks of chronic kidney disease (CKD). Nevertheless, there has been no evidence on associations between long-term exposures to heat waves and CKD as well as the modifying effects of land cover patterns. Based on a national representative population-based survey on CKD covering 47,086 adults and high spatial resolution datasets on temperature and land cover data, we found that annual days of exposure to heat waves were associated with increased odds of CKD prevalence. For one day/year increases in HW_975_4d (above 97.5 % of annual maximum temperature and lasting for at least 4 consecutive days), the odds ratio (OR) of CKD was 1.14 (95 %CI: 1.12, 1.15). Meanwhile, stronger associations were observed in regions with lower urbanicity [rural: 1.14 (95 %CI: 1.12, 1.16) vs urban: 1.07 (95 %CI: 1.03, 1.11), Pinteraction < 0.001], lower water body coverage [lower: 1.14 (95 %CI: 1.12, 1.16) vs higher: 1.02 (95 %CI: 0.98, 1.05), Pinteraction < 0.001], and lower impervious area coverage [lower: 1.16 (95 %CI: 1.14, 1.18) vs higher: 1.06 (95 %CI: 1.03, 1.10), Pinteraction = 0.008]. In addition, this study found disparities in modifying effects of water bodies and impervious areas in rural and urban settings. In rural regions, the associations between heat waves and CKD prevalence showed a consistent decreasing trend with increases in both proportions of water bodies and impervious areas (Pinteraction < 0.05). Nevertheless, in urban regions, we observed significant effect modification by water bodies, but not by impervious areas. Our study indicates the need for targeted land planning as part of adapting to the kidney impacts of heat waves, with a focus on urbanization in rural regions, as well as water body construction and utilization in both rural and urban regions.
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Cambio Climático , Calor , Insuficiencia Renal Crónica , Urbanización , China/epidemiología , Humanos , Insuficiencia Renal Crónica/epidemiología , Calor/efectos adversos , Masculino , Femenino , Persona de Mediana Edad , Prevalencia , Adulto , AncianoRESUMEN
BACKGROUND: The prevalence of depressive disorder is increasing due to a variety of factors, which brings a huge strain on individuals, families and society. This study aims to investigate whether there is Frontal Theta Asymmetry (FTA) in depressed patients, and whether FTAs are related to depression severity and cognitive function changes in depressed patients. METHODS: Participants who met the inclusion criteria were enrolled in this study. Socio-demographic data of each participant were recorded. Zung's self-rating Depression Scale was used to assess the depression status of participants. P300 was used to evaluate the cognitive function of participants. EEG data from participants were collected by the NeuroScan SynAmps RT EEG system. t-test, Wilcoxon rank-sum test and Chi-square test were used to detect the differences of different variables between the two groups. Multiple linear regression analysis and multiple logistic regression analysis were used to analyze relationships between FTAs in different regions and participants' depression status and cognitive function. RESULTS: A total of 66 depressed participants and 47 healthy control participants were included in this study. The theta spectral power of the left frontal lobe was slightly stronger than that of the right frontal lobe in the depression group, while the opposite was true in the healthy control group. The FTA in F3/F4 had certain effects on the emergence of depression in participants, the emergence of depression in participants and Changes in cognitive function. CONCLUSIONS: FTAs are helpful to assess the severity of depression and early identify cognitive impairment in patients with depression.
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Cognición , Electroencefalografía , Lóbulo Frontal , Ritmo Teta , Humanos , Masculino , Femenino , Ritmo Teta/fisiología , Adulto , Lóbulo Frontal/fisiopatología , Cognición/fisiología , Persona de Mediana Edad , Índice de Severidad de la Enfermedad , Depresión/fisiopatología , Depresión/psicología , Escalas de Valoración Psiquiátrica , Trastorno Depresivo/fisiopatología , Potenciales Relacionados con Evento P300/fisiología , Disfunción Cognitiva/fisiopatologíaRESUMEN
Introduction: A previous study showed that the renal risk score (RRS) was transferrable to antiglomerular basement membrane (anti-GBM) disease and proposed a risk stratification according to the need of renal replacement therapy (RRT) and the percentage of normal glomeruli (N). Herein, we analyzed the risk factors associated with kidney outcomes in patients with biopsy-proven anti-GBM disease and evaluated these 2 prognosis systems. Methods: A total of 120 patients with biopsy-proven anti-GBM disease with complete clinicopathologic and outcome data were analyzed. Results: The median time to kidney biopsy was 41 days (interquartile range [IQR]: 22-63 days). RRT and N were the only independent predictors of end-stage kidney disease (ESKD). Patients with N ≥10% were more likely to achieve ESKD-free outcomes, even in the subcohort of patients who underwent posttreatment biopsies (P < 0.001). N and serum creatinine at presentation (cut-off values 750 µmol/l and 1300 µmol/l) were 2 independent factors for predicting kidney recovery. The RRS and the risk stratification tool exhibited predictive value for ESKD and could be transferred to patients with kidney biopsy following treatment (Harrell's C statistic [C] = 0.738 and C = 0.817, respectively). However, a cross-over of outcomes among groups was observed in the risk stratification tool in long-term follow-up, when patients with RRT and N ≥10% achieved better kidney outcomes than those without RRT but N <10%. Conclusion: Normal glomeruli percentage, even posttreatment, was a strong indicator for kidney outcomes, especially on long-term prognosis. Serum creatinine is a predictor for kidney recovery, independent of biopsy findings. The risk stratification tool for kidney survival was transferrable to patients with anti-GBM disease with biopsy following treatment in our cohort; however, this needs further validations for long-term outcomes.
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Due to the influence of structural clearances, the shearer's oscillates and jumps concerning the scraper are frequent, which induces the collision and vibration impact of the traction components and exacerbates the traction failure of the shearer. Therefore, to explore the correlation between attitude disturbance and traction vibration, an experiment on the traction vibration is carried out, the spatial swaying of the shearer and vibration differences between two traction components are obtained, the influence of the lifting angle of the rocker arm is discussed, and the influence mechanism of the shearer attitude disturbance on traction vibration is elucidated. The results indicate that the rolling swing intensity of the shearer is the highest while the yawing swing intensity is the lowest, and the pitch swing intensity increases with the increase of the lifting angle of the rocker arm. Besides, the vibration impact indices of the two walking mechanisms have a competitive relationship of one decreasing but the other increasing, which can be used as a reference signal to judge the rolling swing and load-sharing performance of the traction part. Moreover, with the swing attitude, the competitive relationship of the average of vibration peaks is shown in the two support shoes, and it can be used as a reference signal to judge the pitching swing and the load-sharing performance of the traction part. This result reveals the impact mechanism of attitude disturbances on traction vibration and proposes a signal monitoring approach for judging the traction attitude disturbance and load-sharing performance, providing a reference for reducing traction faults.
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PURPOSE: This study aimed to investigate the influence of surgical intervention on recurrence risk of upper urinary tract stone and compare the medical burden of various surgical procedures. METHODS: This study analyzed data from patients with upper urinary tract stone extracted from a national database of hospitalized patients in China, from January 2013 to December 2018. Surgical recurrence was defined as patients experience surgical procedures for upper urinary tract stone again with a time interval over 90 days. Associations of surgical procedures with surgical recurrence were evaluated by Cox regression. RESULTS: In total, 556,217 patients with upper urinary tract stone were included in the present analysis. The mean age of the population was 49.9 ± 13.1 years and 64.1% were men. During a median follow-up of 2.7 years (IQR 1.5-4.0 years), 23,012 patients (4.1%) had surgical recurrence with an incidence rate of 14.9 per 1000 person-years. Compared to patients receiving open surgery, ESWL (HR, 1.59; 95% CI 1.49-1.70), URS (HR, 1.38; 95% CI 1.31-1.45), and PCNL (HR, 1.11; 95% CI 1.06-1.18) showed a greater risk for surgical recurrence. Patients receiving ESWL had the shortest hospital stay length and the lowest cost among the 4 procedures. CONCLUSIONS: Compared with open surgery, ESWL, URS, and PCNL are associated with higher risks of surgical recurrence for upper urinary tract stone, while ESWL showed the least medical burden including both expenditure and hospital stay length. How to keep balance of intervention efficacy and medical expenditure is an important issue to be weighed cautiously in clinic practice and studied more in the future.
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Cálculos Renales , Litotricia , Nefrostomía Percutánea , Cálculos Urinarios , Sistema Urinario , Masculino , Humanos , Adulto , Persona de Mediana Edad , Femenino , Cálculos Renales/cirugía , Cálculos Urinarios/epidemiología , Cálculos Urinarios/cirugíaRESUMEN
OBJECTIVE: The impact of the difference between cystatin C- and creatinine-based estimated glomerular filtration rate (eGFRdiff) on diabetic microvascular complications (DMCs) remains unknown. We investigated the associations of eGFRdiff with overall DMCs and subtypes, including diabetic retinopathy (DR), diabetic kidney disease (DKD), and diabetic neuropathy (DN). RESEARCH DESIGN AND METHODS: This prospective cohort study included 25,825 participants with diabetes free of DMCs at baseline (2006 to 2010) from the UK Biobank. eGFRdiff was calculated using both absolute difference (eGFRabdiff) and the ratio (eGFRrediff) between cystatin C- and creatinine-based calculations. Incidence of DMCs was ascertained using electronic health records. Cox proportional hazards regression models were used to evaluate the associations of eGFRdiff with overall DMCs and subtypes. RESULTS: During a median follow-up of 13.6 years, DMCs developed in 5,753 participants, including 2,752 cases of DR, 3,203 of DKD, and 1,149 of DN. Each SD decrease of eGFRabdiff was associated with a 28% higher risk of overall DMCs, 14% higher risk of DR, 56% higher risk of DKD, and 29% higher risk of DN. For each 10% decrease in eGFRrediff, the corresponding hazard ratios (95% CIs) were 1.16 (1.14, 1.18) for overall DMCs, 1.08 (1.05, 1.11) for DR, 1.29 (1.26, 1.33) for DKD, and 1.17 (1.12, 1.22) for DN. The magnitude of associations was not materially altered in any of the sensitivity analyses. CONCLUSIONS: Large eGFRdiff was independently associated with risk of DMCs and its subtypes. Our findings suggested monitoring eGFRdiff in the diabetes population has potential benefit for identification of high-risk patients.
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Diabetes Mellitus Tipo 2 , Nefropatías Diabéticas , Neuropatías Diabéticas , Retinopatía Diabética , Adulto , Humanos , Cistatina C , Creatinina , Estudios de Cohortes , Estudios Prospectivos , Tasa de Filtración Glomerular , Nefropatías Diabéticas/etiología , Retinopatía Diabética/etiología , Retinopatía Diabética/complicaciones , Neuropatías Diabéticas/complicaciones , Factores de Riesgo , Diabetes Mellitus Tipo 2/complicacionesRESUMEN
OBJECTIVES: Chronic kidney disease (CKD) is a global public health concern, and accumulating evidence has indicated that air pollution increases the odds of CKD. However, a limited number of studies have examined the long-term effects of ambient fine particulate matter (PM2.5) components on the risk of CKD among general population; thus, major knowledge gaps remain. METHODS: Using data from a nationwide representative cross-sectional survey in China and a validated PM2.5 composition dataset, we established generalized linear models to quantify the association between five major components of PM2.5 and CKD prevalence. RESULTS: There were significant associations between long-term exposure to three PM2.5 components [including black carbon (BC), sulfate (SO42-), organic matter (OM)] and increased odds of CKD prevalence. Along with an interquartile range (IQR) increment in BC (3.3 µg/m3), SO42- (9.7 µg/m3), and OM (16.2 µg/m3) at a 4-year moving average, the odds ratios (ORs) for CKD prevalence were 1.28 (95% CI 1.07, 1.54), 1.23 (95% CI 1.03, 1.45), and 1.23 (95% CI 1.02, 1.47), respectively. We did not detect any significant association of the other two PM2.5 components [nitrate (NO3-) or ammonium (NH4+)] with CKD prevalence. Stratified analyses revealed no differences (P ≥ 0.05) in the effect estimates of subgroups based on administrative region, sex, age, and other demographic characteristics. For instance, along with an IQR increment in BC at a 4-year moving average, the ORs of CKD prevalence among males and females were 1.30 (95% CI 0.98, 1.73) and 1.29 (95% CI 1.01, 1.65), respectively. The odds of CKD were generally higher with increasing PM2.5 composition concentration. CONCLUSIONS: Our study demonstrated that long-term exposure to specific PM2.5 components including BC, SO42-, and OM increased CKD risk in the general population. This study could provide new insights into source-directed PM2.5 control and CKD prevention.
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Contaminación del Aire , Insuficiencia Renal Crónica , Femenino , Masculino , Humanos , Estudios Transversales , Prevalencia , China/epidemiología , Insuficiencia Renal Crónica/inducido químicamente , Insuficiencia Renal Crónica/epidemiología , HollínRESUMEN
Particulate of diameter ≤ 1 µm (PM1) presents a novel risk factor of adverse health effects. Nevertheless, the association of PM1 with the risk of chronic kidney disease (CKD) in the general population is not well understood, particularly in regions with high PM1 levels like China. Based on a nationwide representative survey involving 47,204 adults and multi-source ambient air pollution inversion data, the present study evaluated the association of PM1 with CKD prevalence in China. The two-year average PM1, particulate of diameter ≤ 2.5 µm (PM2.5), and PM1-2.5 values were accessed using a satellite-based random forest approach. CKD was defined as estimated glomerular filtration rate < 60 ml/min/1.73 m2 or albuminuria. The results suggested that a 10 µg/m3 rise in PM1 was related to a higher CKD risk (odds ratio [OR], 1.13; 95% confidence interval [CI] 1.08-1.18) and albuminuria (OR, 1.11; 95% CI, 1.05-1.17). The association between PM1 and CKD was more evident among urban populations, older adults, and those without comorbidities such as diabetes or hypertension. Every 1% increase in the PM1/PM2.5 ratio was related to the prevalence of CKD (OR, 1.03; 95% CI, 1.03-1.04), but no significant relationship was found for PM1-2.5. In conclusion, the present study demonstrated long-term exposure to PM1 was associated with an increased risk of CKD in the general population and PM1 might play a leading role in the observed relationship of PM2.5 with the risk of CKD. These findings provide crucial evidence for developing air pollution control strategies to reduce the burden of CKD.
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Contaminantes Atmosféricos , Contaminación del Aire , Insuficiencia Renal Crónica , Humanos , Anciano , Contaminantes Atmosféricos/toxicidad , Contaminantes Atmosféricos/análisis , Material Particulado/toxicidad , Prevalencia , Albuminuria/epidemiología , Albuminuria/inducido químicamente , Exposición a Riesgos Ambientales/análisis , Contaminación del Aire/análisis , Polvo , China/epidemiología , Insuficiencia Renal Crónica/epidemiologíaRESUMEN
BACKGROUND: To explore the association between the differences between cystatin C- and creatinine-based estimated glomerular filtration rate (eGFRdiff), and the risk of mortality and cardiovascular (CV) events in individuals with diabetes. METHODS: Three prospective cohorts analyzed data from adults with diabetes from the Incident, Development, and Prognosis of Diabetic Kidney Disease (INDEED) study (2016-17 to 2020) in China, the National Health Nutrition Examination Survey (NHANES, 1999-2004 to 2019) in the USA and UK Biobank (UKB, 2006-10 to 2022) in the UK. Baseline eGFRdiff was calculated using both absolute difference between cystatin C- and creatinine-based calculations (eGFRabdiff), and the ratio between them (eGFRrediff). Cox proportional hazards regression models were used to investigate the association between eGFRdiff and outcomes including all-cause mortality and incident CV events. RESULTS: A total of 8129 individuals from INDEED (aged 60.7 ± 10.0 years), 1634 from NHANES (aged 62.5 ± 14.4 years) and 29 358 from UKB (aged 59.4 ± 7.3 years) were included. At baseline, 43.6%, 32.4% and 42.1% of participants in INDEED, NHANES and UKB, respectively, had an eGFRabdiff value ≥15 mL/min/1.73 m2. During a median follow-up of 3.8 years for INDEED, 15.2 years for NHANES and 13.5 years for UKB, a total of 430, 936 and 6143 deaths and a total of 481, 183 and 5583 CV events occurred, respectively. Each 1-standard deviation higher baseline eGFRabdiff was independently associated with a lower risk of all-cause mortality and CV events, with hazard ratios of 0.77 and 0.82 in INDEED, 0.70 and 0.68 in NHANES, and 0.66 and 0.78 in UKB. Similar results were observed for eGFRrediff. CONCLUSIONS: eGFRdiff represents a marker of adverse events for diabetes among general population. Monitoring both eGFRcys and eGFRcr yields additional prognostic information and has clinical utility in identifying high-risk individuals for mortality and CV events.
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Enfermedades Cardiovasculares , Creatinina , Cistatina C , Tasa de Filtración Glomerular , Humanos , Cistatina C/sangre , Persona de Mediana Edad , Femenino , Masculino , Enfermedades Cardiovasculares/mortalidad , Enfermedades Cardiovasculares/etiología , Enfermedades Cardiovasculares/diagnóstico , Creatinina/sangre , Estudios Prospectivos , Anciano , China/epidemiología , Pronóstico , Nefropatías Diabéticas/mortalidad , Nefropatías Diabéticas/diagnóstico , Nefropatías Diabéticas/fisiopatología , Nefropatías Diabéticas/etiología , Biomarcadores/sangre , Encuestas Nutricionales , Diabetes Mellitus/mortalidad , Factores de RiesgoRESUMEN
Objectives: This study aimed to explore the influence of depression severity, disease course, treatment status, and other factors on cognitive function in adolescents with depressive disorders. Methods: Participants who met the inclusion criteria were enrolled in the study. Sociodemographic data of each participant were recorded, including age, sex, and family history of mental disorders. Zung's Self-Rating Depression Scale was used to assess depression status in adolescents. Moreover, P300 and mismatch negativity (MMN) were used to objectively evaluate the participants' cognitive function. Results: Only 26.8% of the adolescents with depression received standard antidepressant treatment. The latencies of N2 (267.80±23.34 ms), P3 (357.71±32.09 ms), and MMN (212.10±15.61 ms) in the adolescent depression group were longer than those in the healthy control group (p<0.01). Further analysis revealed that the latency of MMN was extended with increased levels of depression in adolescents. The MMN latency was short in participants with depression receiving standardized treatment. Furthermore, the latency of MMN was positively correlated with the severity and duration of depression (correlation coefficients were 0.465 and 0.479, respectively) (p<0.01). Conclusion: Receiving standardized treatment and shortening the course of depression can reduce cognitive impairment in adolescents with depression.
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Disección Aórtica , Humanos , Disección Aórtica/cirugía , Disección Aórtica/diagnóstico por imagen , Disección Aórtica/complicaciones , Masculino , Aneurisma de la Aorta/diagnóstico por imagen , Aneurisma de la Aorta/cirugía , Aneurisma de la Aorta/complicaciones , Persona de Mediana Edad , Tomografía Computarizada por Rayos X , Aneurisma de la Aorta Torácica/cirugía , Aneurisma de la Aorta Torácica/diagnóstico por imagen , Aneurisma de la Aorta Torácica/complicaciones , Aneurisma de la Aorta Torácica/diagnósticoRESUMEN
Blood pressure(BP) of the longevous population with hypertension and/or frailty was under-investigated. To investigate the association between age, BP, variation of BP, and survival among the old adults with different status of hypertension and frailty, the present study included adults ≥65 years in the Chinese Longitudinal Healthy Longevity Survey (2008-2018), defined frailty using the Fried criteria, and identified hypertension by self-report or SBP/DBP ≥ 140/90 mm Hg. The association between age and BP were investigated using linear regression models. Variation of BP was defined if annual change of BP lower than quartile 1(sharp decrease) or higher than quartile 3(sharp increase). The association between age and BP variation were investigated using multinominal logistic regression models. The association between BP and survival was analyzed using Cox regression models. Among 13,447 adults (centenarian: 1965[14.6%]), age was positively associated with SBP in robust hypertensive elderly but negatively associated with it in frail hypertensive elderly. Annual change of BP was more likely to be increment among the normotensive elderly, but be decrement among the hypertensive elderly, especially among those with frailty. SBP < 120 mmHg was the risk factor of mortality among the frail oldest-old (≥85 years) while SBP ≥ 150 mmHg was that among the robust young-old (65-84 years). DBP ≥ 90 mmHg was the risk factor of mortality both in the robust young-old and the frail oldest old. In conclusion, age and frailty might be the criteria to predict the change of BP to guide the BP management of the longevous population.
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Fragilidad , Hipertensión , Adulto , Anciano de 80 o más Años , Anciano , Humanos , Presión Sanguínea/fisiología , Fragilidad/epidemiología , Hipertensión/epidemiología , Anciano Frágil , Factores de RiesgoRESUMEN
With the rapid growth and widespread application of electronic health records (EHRs), similar patient retrieval has become an important task for downstream clinical decision support such as diagnostic reference, treatment planning, etc. However, the high dimensionality, large volume, and heterogeneity of EHRs pose challenges to the efficient and accurate retrieval of patients with similar medical conditions to the current case. Several previous studies have attempted to alleviate these issues by using hash coding techniques, improving retrieval efficiency but merely exploring underlying characteristics among instances to preserve retrieval accuracy. In this paper, drug categories of instances recorded in EHRs are regarded as the ground truth to determine the pairwise similarity, and we consider the abundant semantic information within such multi-labels and propose a novel framework named Graph-guided Deep Hashing Networks (GDHN). To capture correlation dependencies among the multi-labels, we first construct a label graph where each node represents a drug category, then a graph convolution network (GCN) is employed to derive the multi-label embedding of each instance. Thus, we can utilize the learned multi-label embeddings to guide the patient hashing process to obtain more informative and discriminative hash codes. Extensive experiments have been conducted on two datasets, including a real-world dataset concerning IgA nephropathy from Peking University First Hospital, and a publicly available dataset from MIMIC-III, compared with traditional hashing methods and state-of-the-art deep hashing methods using three evaluation metrics. The results demonstrate that GDHN outperforms the competitors at different hash code lengths, validating the superiority of our proposal.
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Benchmarking , Registros Electrónicos de Salud , Humanos , Aprendizaje , SemánticaRESUMEN
The supply level of exogenous nitrogen has a very important influence on the growth and development of cucumber. Insufficient or excessive nitrogen application will lead to metabolic disorders in the body and affect the formation of yield. Therefore, it is of great scientific and practical significance to explore the corresponding mitigation measures. Melatonin (MT) is a multi-regulatory molecule with pleiotropic effects on plant growth and development. A large number of studies have shown that the appropriate amount of melatonin supplementation is beneficial to plant growth and development by promoting root development, delaying leaf senescence, and improving fruit yield. However, the study of MT function combined with a detailed physiological analysis of nitrogen (N) absorption and metabolism in cucumber plants needs further strengthening. We performed hydroponic tests at different nitrogen levels to determine the metabolic processes associated with the enhanced tolerance to nitrogen in melatonin-treated cucumber (Cucucumis sativus L.) seedlings. Cucumber seedlings were sprayed with 100 µM melatonin or water and treated with different nitrogen in the growth chamber for 7 days. Nitrogen deficiency significantly inhibited seedling growth, and this growth inhibition was partially alleviated by melatonin. The expression analysis of related carbon and nitrogen genes showed that the genes whose expression was significantly altered by melatonin were mainly related to carbon (C) and nitrogen (N) metabolism. By enzyme activity and reactive oxygen content data analysis, melatonin-treated cucumber seedlings showed relatively stable carbon and nitrogen levels compared to untreated ones. In conclusion, MT can repair the impaired growth and development situation by regulating the nitrogen assimilation capacity and the balance between oxidation and oxidative metabolism and carbon metabolism in the cucumber under different nitrogen levels.
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Cucumis sativus , Melatonina , Plantones/metabolismo , Cucumis sativus/metabolismo , Melatonina/farmacología , Melatonina/metabolismo , Nitrógeno/metabolismo , Carbono/metabolismoRESUMEN
Starch-lipid-protein complexes are attracting increasing attention due to their unique structure and low enzymatic digestibility. However, the mechanisms underlying the formation of these ternary complexes, especially those with monoglycerides as the lipid component, remain unclear. In the present study, potato starch or octenyl succinic anhydride (OSA)-modified potato starch (OSAPS), various monoglycerides (MGs), and beta-lactoglobulin (ßLG) were used in model systems to characterize the formation, structure, and in vitro digestibility of the respective ternary complexes. Colorimetry and live/dead staining assays demonstrated that the OSAPS had good biocompatibility. Experimental data and molecular dynamics simulations showed that both unmodified potato starch and OSAPS formed starch-lipid-protein complexes with MGs and ßLG. Of the two types of starch, OSA formed a greater amount of the more stable type II V-crystallites in complexes, which had greater resistance to in vitro enzymic digestion. This study demonstrated for the first time that starch can interact with MGs and ßLG to form ternary complexes and that OSA esterification of starch promoted the formation of more complexes than unmodified starch.
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Monoglicéridos , Anhídridos Succínicos , Anhídridos Succínicos/química , Almidón/química , EsterificaciónRESUMEN
BACKGROUND: Kidney involvement is common in hospitalized coronavirus disease 2019 (COVID-19) patients during the acute phase, little is known about the long-term impact of COVID-19 on the kidney. METHODS: This is a systematic review and meta-analysis on long-term renal outcomes among COVID-19 patients. We carried out a systematic literature search in PUBMED, EMBASE, SCOPUS, and Cochrane COVID-19 study register and performed the random-effects meta-analysis of rates. The search was last updated on November 23, 2022. RESULTS: The study included 12 moderate to high-quality cohort studies involving 6976 patients with COVID-19-associated acute kidney injury and 5223 COVID-19 patients without acute kidney injury. The summarized long-term renal non-recovery rate, dialysis-dependent rate, and complete recovery rate among patients with COVID-19-associated AKI was 22% (12-33%), 6% (2-12%), and 63% (44-81%) during a follow-up of 90-326.5 days. Heterogeneity could be explained by differences in the prevalence of chronic kidney disease and proportion of acute kidney injury requiring renal replacement therapy using meta-regression; patients with more comorbidities or higher renal replacement therapy rate had higher non-recovery rates. The summarized long-term kidney function decrease rate among patients without acute kidney injury was 22% (3-51%) in 90-199 days, with heterogeneity partially explained by severity of infection. CONCLUSION: Patients with more comorbidities tend to have a higher renal non recovery rate after COVID-19-associated acute kidney injury; for COVID-19 patients without acute kidney injury, decrease in kidney function may occur during long-term follow-up. Regular evaluation of kidney function during the post-COVID-19 follow-up among high-risk patients may be necessary.