Intraindividual difference in estimated GFR by creatinine and cystatin C, cognitive trajectories and motoric cognitive risk syndrome.

BACKGROUND: Intraindividual differences between estimated glomerular filtration rate (eGFR) based on cystatin C (eGFRcys) and creatinine (eGFRcr) can convey important clinical information regarding the health status. However, the clinical implications of these differences (eGFRdiff) for risk of cognitive decline and motoric cognitive risk syndrome (MCR) remains unclear. We aimed to investigate the longitudinal associations of eGFRdiff with cognitive trajectories and incident MCR. METHODS: Based on the China Health and Retirement Longitudinal Study, we identified two study sub-cohorts: one for cognitive trajectory follow-up (6423 participants; years:2011-2018) and another for incident MCR follow-up (2477 participants; years:2011-2015). The eGFRdiff was defined as eGFRcys minus eGFRcr. Adjusted ordinal and binary logistics regression models were separately used to assess the associations of eGFRdiff with cognitive trajectories and incident MCR. We also performed discordance analyses for eGFRdiff vs eGFRcys, eGFRcr or eGFR based on both creatinine and cystatin C (eGFRcys-cr). RESULTS: In the first sub-cohort, four distinct 7-year cognitive trajectories were identified. Each 1-SD higher eGFRdiff (value for eGFRcys minus eGFRcr) was associated with a lower risk of poorer cognitive trajectories (OR: 0.909, 95% CI: 0.877-0.942). In the second sub-cohort, 121 participants developed incident MCR after a 4-year follow-up. Each 1-SD higher eGFRdiff (value for eGFRcys minus eGFRcr) was linked with a 25.3% (95%CI: 16.6%-33.2%) decreased risk for MCR. The above associations persisted in individuals with normal kidney function. Additionally, the risk for cognitive decline and incident MCR was more strongly associated with eGFRcys than eGFRcr and eGFRcys-cr. For the discordance analyses, 'discordantly high eGFRdiff/low eGFR' group, but not 'discordantly low eGFRdiff/high eGFR', exhibited a significantly lower risk of poorer cognitive trajectories and MCR compared to the concordant group. CONCLUSIONS: A large negative difference between eGFRcys and eGFRcr (eGFRcys lower than eGFRcr) was associated with higher risk of cognitive decline and incident MCR. The eGFRdiff could capture additional valuable risk information beyond eGFRcys, eGFRcr, and eGFRcys-cr.

Separate and Joint Associations of Remnant Cholesterol Accumulation and Variability With Carotid Atherosclerosis: A Prospective Cohort Study.

Background We aimed to examine separate and joint associations of remnant cholesterol (RC) accumulation and variability with the risk of carotid atherosclerosis (CAS) in the general population. Methods and Results A total of 6213 participants who underwent 3 sequential health examinations during 2010 to 2015 were enrolled and were followed up until December 31, 2021. Cumulative RC (cumRC) and RC variability among the 3 visits were the exposure of interest in our study. Adjusted Cox models were performed to calculate the hazard ratio (HR) and 95% CI. C-statistics, integrated discrimination improvement, and the net reclassification index were used to estimate the incremental predictive ability. During a median follow-up of 4.00 years, 2613 participants developed CAS. Higher cumRC (HR, 1.33 [95% CI, 1.17-1.52]) and greater RC variability (HR, 1.22 [95% CI, 1.08-1.39]) were significantly associated with elevated risk of CAS, independent of traditional cardiovascular risk factors and low-density lipoprotein cholesterol. Participants were divided into 4 groups according to the median of cumRC and RC variability to assess their joint associations. Compared with "low cumRC and low variability," "high cumRC and high variability" had the highest risk of CAS, followed by "high cumRC and low variability" and "low cumRC and high variability." Finally, joint assessment of RC accumulation and variability had the significantly highest incremental effect on the predictive value of CAS versus single-time-point measures of RC. Conclusions Excessive cumRC levels and greater RC variability were each independently associated with higher incidence of CAS, and their coexistence could further yield significantly higher risks.

Association Between Long-Term Exposure to Fine Particulate Matter Constituents and Progression of Cerebral Blood Flow Velocity in Beijing: Modifying Effect of Greenness.

Few studies have explored the effects of fine particulate matter (PM2.5) and its constituents on the progression of cerebral blood flow velocity (BFV) and the potential modifying role of greenness. In this study, we investigated the association of PM2.5 and its constituents, including sulfate (SO4 2-), nitrate (NO3 -), ammonium (NH4 +), organic matter (OM), and black carbon (BC), with the progression of BFV in the middle cerebral artery. Participants from the Beijing Health Management Cohort who underwent at least two transcranial Doppler sonography examinations during 2015-2020 were recruited. BFV change and BFV change rate were used to define the progression of cerebral BFV. Linear mixed effects models were employed to analyze the data, and the weighted quantile sum regression assessed the contribution of PM2.5 constituents. Additionally, greenness was examined as a modifier. Among the examined constituents, OM exhibited the strongest association with BFV progression. An interquartile range increase in PM2.5 and OM exposure concentrations was associated with a decrease of -16.519 cm/s (95% CI: -17.837, -15.201) and -15.403 cm/s (95% CI: -16.681, -14.126) in BFV change, and -10.369 cm/s/year (95% CI: -11.387, -9.352) and -9.615 cm/s/year (95% CI: -10.599, -8.632) in BFV change rate, respectively. Furthermore, stronger associations between PM2.5 and BFV progression were observed in individuals working in areas with lower greenness, those aged under 45 years, and females. In conclusion, reducing PM2.5 levels in the air, particularly the OM constituent, and enhancing greenness could potentially contribute to the protection of cerebrovascular health.

Associations of time-weighted individual exposure to ambient particulate matter with carotid atherosclerosis in Beijing, China.

BACKGROUND: Time-location information (time spent on commuting, indoors and outdoors around residential and work places and physical activity) and infiltrated outdoor pollution was less considered estimating individual exposure to ambient air pollution. Studies investigating the association between individual exposure to particulate matter (PM) with aerodynamic diameter < 10 µm (PM10) and < 2.5 µm (PM2.5) and carotid atherosclerosis presented inconsistent results. Moreover, combined effect of pollutants on carotid atherosclerosis was not fully explored. We aimed to investigate the association between long-term individual time-weighted average exposure to PM2.5 and PM10 and the risk of carotid atherosclerosis, and further explore the overall effect of co-exposure to pollutants on carotid atherosclerosis. METHODS: The study population included 3069 participants derived from the Beijing Health Management Cohort (BHMC) study. Daily concentration of ambient air pollutants was estimated by land-use regression model at both residential and work addresses, and one- and two-year time-weighted average individual exposure was calculated by further considering personal activity pattern and infiltration of ambient air pollution indoors. We explored the association of PM2.5 and PM10 with carotid atherosclerosis and pooled the overall effect of co-exposure to ambient air pollutants by quantile g-computation. RESULTS: A significant association between time-weighted average exposure to PM2.5 and PM10 and carotid atherosclerosis was observed. Per interquartile range increase in two-year exposure to PM2.5 (Hazard ratio (HR): 1.322, 95% confidence interval (CI): 1.219-1.434) and PM10 (HR:1.213, 95% CI: 1.116-1.319) showed the strongest association with carotid atherosclerosis, respectively. Individuals in higher quartiles of pollutants were at higher risk for carotid atherosclerosis compared with those in the lowest quartile group. Concentration response functions documented the nearly linear and nonlinear relationship and interpreted the upward trends of the risk for carotid atherosclerosis with increasing level of pollutant concentrations. Moreover, effect estimates for the mixture of pollutants and carotid atherosclerosis were larger than any of the individual pollutants (HR (95% CI) was 1.510 (1.338-1.704) and 1.613 (1.428-1.822) per quartile increase for one-year and two-year time-weighted average exposure, respectively). CONCLUSIONS: Individual time-weighted average exposure to PM2.5 and PM10 was associated with carotid atherosclerosis. Co-exposure to ambient air pollution was also positively associated with carotid atherosclerosis.

Bidirectional Associations between Daytime Napping Duration and Metabolic Syndrome: A Nationally Representative Cohort Study.

BACKGROUND: We aimed to examine the bidirectional associations between daytime napping duration and metabolic syndrome (MetS). METHODS: Using data from the China Health and Retirement Longitudinal Study from 2011 to 2015, modified Poisson regression models were performed to explore the longitudinal associations of baseline napping duration with the occurrence and remission of MetS. Generalized estimating equation was conducted to explore the association between baseline MetS status with subsequent changes in daytime napping duration. Cross-lagged panel analysis was performed to further verify their bidirectional relationships. RESULTS: During the four-year follow-up, among 5041 participants without MetS at baseline, extended naps were significantly associated with MetS occurrence, compared with non-napping. This association was only significant in individuals with adequate night-time sleep duration or good sleep quality of the 2898 participants with MetS at baseline. Excessive napping duration may be not favorable for MetS remission especially for adequate night-time sleepers. With respect to reverse associations, baseline MetS status significantly increased the napping duration during the subsequent follow-up period. Finally, there were significant bidirectional cross-lagged associations between napping duration and MetS severity score after adjusting for all covariates. CONCLUSIONS: Our study indicates bidirectional relationships exist between daytime napping duration and MetS. Interestingly, longer napping duration was detrimental to cardiometabolic health only in those with sufficient night-time sleep duration or good sleep quality.

Combined evaluation of arterial stiffness, glycemic control and hypertension for macrovascular complications in type 2 diabetes.

BACKGROUND: Arterial stiffness, glycemic control and blood pressure are risk factors of macrovascular complications in type 2 diabetes. This study aimed to investigate the combined association of arterial stiffness, glycemic control and hypertension status with the occurrence of diabetic macrovascular complication. METHODS: A total of 1870 patients of diabetes were enrolled from Beijing Health Management Cohort between 2008 and 2018 as baseline, and then followed for macrovascular complication onset. We proposed a composite risk score (0-4) by arterial stiffness severity, pool glycemic control and hypertension status. Cox model was used to estimate the hazard ratio (HR) and 95% confidence interval (CI). RESULTS: The mean age (SD) of this population was 59.90 (12.29) years. During a median follow-up of 4.0 years, 359 (19.2%) patients developed macrovascular complication. Compared to the normal arterial stiffness and good glycemic control group, patients with severe arterial stiffness and pool glycemic control had the highest risk of macrovascular complications (HR: 2.73; 95% CI: 1.42-5.25). Similarly, those of severe arterial stiffness and hypertension had the highest risk (HR: 2.69; 95% CI: 1.61-4.50). Patients of the composite score > 2 had a significantly increased risk of macrovascular complication. CONCLUSION: This study suggested the clinical importance of combined evaluation of arterial stiffness, glycemic control and hypertension status for the risk stratification and management of macrovascular complication of type 2 diabetes.

Association of baseline and cumulative remnant cholesterol with incidence of diabetic nephropathy: A longitudinal cohort study.

AIMS: To evaluate the longitudinal association of remnant cholesterol with the incidence of diabetic nephropathy using a Chinese diabetes cohort. METHODS: We included 4237 individuals with type 2 diabetes during 2013-2014 from Beijing Health Management Cohort. Remnant cholesterol was defined by Martin-Hopkins equation. Diabetic nephropathy was confirmed by urine albumin/creatinine ratio and estimated glomerular filtration rate. We calculated the hazard ratio (HR) and 95% confidence interval (CI) for incident diabetic nephropathy using adjusted Cox proportional hazards regression. RESULTS: The median [IQR] age was 55 [48, 64] years, and 3 256 (76.8 %) were men. During follow-up, 248 (5.9 %) participants developed diabetic nephropathy. One-SD increase of baseline and average cumulative remnant cholesterol were significantly associated with an increased risk of diabetic nephropathy, and the adjusted HRs were 1.208 (95 % CI: 1.098-1.329) and 1.216 (95 % CI: 1.102-1.341), respectively. Individuals in the highest tertile of baseline and average cumulative remnant cholesterol had a 82.3 % and 87.6 % excess risk of diabetic nephropathy, compared with those in the lowest. CONCLUSION: Remnant cholesterol is independently associated with incident diabetic nephropathy in type 2 diabetes.

Moderate increase of serum uric acid within a normal range is associated with improved cognitive function in a non-normotensive population: A nationally representative cohort study.

Background: Associations between serum uric acid (SUA) and changes in cognitive function are understudied in non-normotensive populations, and many previous studies only considered the baseline SUA at a single time point. We aimed to examine the effects of baseline SUA and 4-year changes in SUA on cognitive changes in the non-normotensive population. Materials and methods: In the China Health and Retirement Longitudinal Study (CHARLS), cognitive function was measured based on executive function and episodic memory in four visits (years: 2011, 2013, 2015, and 2018). We identified two study cohorts from CHARLS. The first cohort included 3,905 non-normotensive participants. Group-based single-trajectory and multi-trajectory models were applied to identify 7-year cognitive trajectories. Adjusted ordinal logistics models were performed to assess the association between baseline SUA and 7-year cognitive trajectories, and subgroup analyses were conducted according to the presence of hyperuricemia or SUA levels. The second cohort included 2,077 eligible participants. Multiple linear regression was used to explore the effect of a 4-year change in SUA on cognitive change during the subsequent 3-year follow-up. Results: Four distinct single-trajectories of global cognitive performance and four multi-trajectories of executive function and episodic memory were identified. Higher baseline SUA levels were significantly associated with more favorable cognitive single-trajectories (OR Q4 vs. Q1: 0.755; 95% CI: 0.643, 0.900) and multi-trajectories (OR Q4 vs. Q1: 0.784; 95% CI: 0.659, 0.933). Subgroup analyses revealed that the protective effect of SUA was significant in the non-hyperuricemia groups or the low-level SUA groups. Additionally, changes in SUA could influence future cognitive changes. Compared with non-hyperuricemia participants with elevated SUA, non-hyperuricemia participants with decreased SUA and patients with persistent hyperuricemia had a higher risk for cognitive decline. Furthermore, only the Q3 group of changes in SUA could enhance global cognitive function compared with the Q1 group (ß: 0.449; 95% CI: 0.073, 0.826). Conclusion: Our study indicates that the maintenance of normal SUA levels and a moderate increase of SUA were advantageous in improving cognitive function or trajectories in a non-normotensive population. Conversely, SUA may impair cognitive function in patients with persistent hyperuricemia.

Association of visceral adiposity index with incident nephropathy and retinopathy: a cohort study in the diabetic population.

BACKGROUND: The association between visceral adiposity index (VAI) and diabetic complications has been reported in cross-sectional studies, while the effect of VAI on complication development remains unclear. This study aims to evaluate the longitudinal association of VAI and Chinese VAI (CVAI) with the incidence of diabetic nephropathy and retinopathy using a Chinese cohort. METHODS: A total of 8 948 participants with type 2 diabetes from Beijing Health Management Cohort were enrolled during 2013-2014, and followed until December 31, 2019. Nephropathy was confirmed by urine albumin/creatinine ratio and estimated glomerular filtration rate; retinopathy was diagnosed using fundus photograph. RESULTS: The mean (SD) age was 53.35 (14.66) years, and 6 154 (68.8%) were men. During a median follow-up of 4.82 years, 467 participants developed nephropathy and 90 participants developed retinopathy. One-SD increase in VAI and CVAI levels were significantly associated with an increased risk of nephropathy, and the adjusted hazard ratios (HR) were 1.127 (95% CI 1.050-1.210) and 1.165 (95% CI 1.003-1.353), respectively. On contrary, VAI and CVAI level were not associated with retinopathy after adjusting confounding factors. CONCLUSION: VAI and CVAI are independently associated with the development of nephropathy, but not retinopathy in Chinese adults with diabetes.

Construction of two Listeria ivanovii attenuated strains expressing Mycobacterium tuberculosis antigens for TB vaccine purposes.

Bacillus Calmette-Guerin (BCG) has failed in complete control of tuberculosis (TB), thus, novel tuberculosis vaccines are urgently needed. We have constructed several TB vaccine candidates, which are characterized by the use of Listeria ivanovii (LI) strain as an antigen delivery vector. Two L. ivanovii attenuated recombinant strains L. ivanovii△actAplcB-Rv0129c and L. ivanovii△actAplcB-Rv3875 were successfully screened. Results from genome PCR and sequencing showed that the Mycobacterium tuberculosis antigen gene cassette coding for Ag85C or ESAT-6 protein respectively had been integrated into LI genome downstream of mpl gene. Western blot confirmed the secretion of Ag85C or ESAT-6 protein from the recombinant LI strains. These two recombinant strains showed similar growth curves as wide type strain in vitro. In vivo, they transiently propagated in mice spleen and liver, and induced specific CD8(+) IFN-γ secretion. Therefore, in this paper, two novel LI attenuated strains expressing specific TB antigens were successfully constructed. The promising growth characteristics in mice immune system and the capability of induction of IFN-γ secretion make them of potential interest for development of TB vaccines.

[Intervention effect of probiotic bifidobacterium on type 2 diabetes mellitus rats].

OBJECTIVE: To observe the influences of bifidobacterium on glucose and lipid metabolism and intestinal flora in type 2 diabetes mellitus rats. METHODS: Rats were randomly divided into 4 groups, the blank control group was fed with basic forage, the other 3 groups were fed with high fat diet. Meanwhile the high-dose and low-dose groups were gavage administrated with 12 and 4 ml/(kg x d) probiotic bifidobacterium for 6 weeks, then, injected with low dose of streptozotocin (20 mg/kg). All rats were sacrificed 2 weeks later, blood and feces samples were collected to analyse. RESULTS: Compared with rats of type 2 diabetes model, glucose concentrations and serum concentrations of FFA, TG, LDL-C of 2 experimental groups were significantly lower, serum concentrations of HDL-C were higher, insulin sensitivity index was higher, content of bifidobacterium was higher, but there were no significant differences in other 5 bacteria. CONCLUSION: The probiotic bifidobacterium could significantly ameliorate the disorder of glucose and lipid metabolism, increase the amount of bifidobacterium of type 2 diabetes rats.