Elevated serum uric acid is associated with cognitive improvement in older American adults: A large, population-based-analysis of the NHANES database

BackgroundThe many studies revealing a connection between serum uric acid (SUA) and dementia have reported conflicting results. This study sought to investigate the relations between SUA and cognitive function in older adults.Materials and methodsThe sample was 2,767 American adults aged ≥60 years from the National Health and Nutrition Examination Survey 2011–2014. Cognitive performance was evaluated by the Consortium to Establish a Registry for Alzheimer’s Disease test, animal fluency test, digit symbol substitution test, and composite z-score. Multivariate linear regression analyses were conducted to estimate the association between SUA and cognitive function.ResultsSUA level and cognitive function were significantly, positively correlated. Age significantly correlated with the association between SUA and cognitive function.ConclusionThese findings support a connection between SUA and cognition, showing a positive link between SUA and cognitive scores among older American adults. We contend that a slight rise in uric acid within the normal range is advantageous for enhanced cognition. To confirm the precise dose-time-response relation, more tests will be needed

Efficacy and safety of low-dose IL-2 in the treatment of systemic lupus erythematosus: A randomised, double-blind, placebo-controlled trial

Objectives Open-labelled clinical trials suggested that low-dose IL-2 might be effective in treatment of systemic lupus erythematosus (SLE). A double-blind and placebocontrolled trial is required to formally evaluate the safety and efficacy of low-dose IL-2 therapy. Methods A randomised, double-blind and placebocontrolled clinical trial was designed to treat 60 patients with active SLE. These patients received either IL-2 (n=30) or placebo (n=30) with standard treatment for 12 weeks, and were followed up for additional 12 weeks. IL-2 at a dose of 1 million IU or placebo was administered subcutaneously every other day for 2 weeks and followed by a 2-week break as one treatment cycle. The primary endpoint was the SLE Responder Index-4 (SRI-4) at week 12. The secondary endpoints were other clinical responses, safety and dynamics of immune cell subsets. Results At week 12, the SRI-4 response rates were 55.17% and 30.00% for IL-2 and placebo, respectively (p=0.052). At week 24, the SRI-4 response rate of IL-2 group was 65.52%, compared with 36.67% of the placebo group (p=0.027). The primary endpoint was not met at week 12. Low-dose IL-2 treatment resulted in 53.85% (7/13) complete remission in patients with lupus nephritis, compared with 16.67% (2/12) in the placebo group (p=0.036). No serious infection was observed in the IL-2 group, but two in placebo group. Besides expansion of regulatory T cells, low-dose IL-2 may also sustain cellular immunity with enhanced natural killer cells. Conclusions Low-dose IL-2 might be effective and tolerated in treatment of SThe work was supported by the National Natural Science Foundation of China (31530020,31570880,81471601,81601417 and 81701598), Peking-Tsinghua Center for Life Sciences to ZG LI, Beijing Sci-Tech Committee Z171100000417007,Clinical Medicine Plus X-Young Scholars Project of Peking University (PKU2019LCXQ013) supported by the Fundamental Research Funds for the Central Universities, Beijing Nova Program Z171100001117025, National Key Research and Development Program of China (2017YFC0909003 to DY), BellberryViertel Senior Medical Research Fellowship to DY and Beijing SL PHARM

Exploration and Clinical Verification of the Blood Co-Expression Genes of Type 2 Diabetes Mellitus and Mild Cognitive Dysfunction in the Elderly

With the development of society, the incidence of dementia and type 2 diabetes (T2DM) in the elderly has been increasing. Although the correlation between T2DM and mild cognitive impairment (MCI) has been confirmed in the previous literature, the interaction mechanism remains to be clarified. To explore the co-pathogenic genes in the blood of MCI and T2DM patients, clarify the correlation between T2DM and MCI, achieve the purpose of early disease prediction, and provide new ideas for the prevention and treatment of dementia. We downloaded T2DM and MCI microarray data from GEO databases and identified the differentially expressed genes associated with MCI and T2DM. We obtained co-expressed genes by intersecting differentially expressed genes. Then, we performed GO and KEGG enrichment analysis of co-DEGs. Next, we constructed the PPI network and found the hub genes in the network. By constructing the ROC curve of hub genes, the most valuable genes for diagnosis were obtained. Finally, the correlation between MCI and T2DM was clinically verified by means of a current situation investigation, and the hub gene was verified by qRT-PCR. A total of 214 co-DEGs were selected, 28 co-DEGs were up-regulated, and 90 co-DEGs were down-regulated. Functional enrichment analysis showed that co-DEGs were mainly enriched in metabolic diseases and some signaling pathways. The construction of the PPI network identified the hub genes in MCI and T2DM co-expression genes. We identified nine hub genes of co-DEGs, namely LNX2, BIRC6, ANKRD46, IRS1, TGFB1, APOA1, PSEN1, NPY, and ALDH2. Logistic regression analysis and person correlation analysis showed that T2DM was correlated with MCI, and T2DM increased the risk of cognitive impairment. The qRT-PCR results showed that the expressions of LNX2, BIRC6, ANKRD46, TGFB1, PSEN1, and ALDH2 were consistent with the results of bioinformatic analysis. This study screened the co-expressed genes of MCI and T2DM, which may provide new therapeutic targets for the diagnosis and treatment of diseases

Effects of Peroxisome Proliferator-Activated Receptor-Gamma Agonists on Cognitive Function: A Systematic Review and Meta-Analysis

Diabetes mellitus (DM) is known to be a risk factor for dementia, especially in the elderly population, and close associations between diabetes and Alzheimer disease (AD) have been determined. Peroxisome proliferator-activated receptor-gamma (PPAR-γ) agonists are insulin-sensitising drugs. In addition to their anti-diabetic properties, their effectiveness in preventing and decreasing cognitive impairment are the most recent characteristics that have been studied. For this study, we conducted a systematic review and meta-analysis to critically analyse and evaluate the existing data on the effects of PPAR-γ agonist therapy on the cognitive status of patients. For this purpose, we first analysed both early intervention and later treatment with PPAR-γ agonists, according to the disease status. The involved studies indicated that early PPAR-γ agonist intervention is beneficial for patients and that high-dose PPAR-γ therapy may have a better clinical effect, especially in reversing the effects of cognitive impairment. Furthermore, the efficacy of pioglitazone (PIO) seems to be promising, particularly for patients with comorbid diabetes. PIO presented a better clinical curative effect and safety, compared with rosiglitazone (RSG). Thus, PPAR-γ agonists play an important role in the inflammatory response of AD or DM patients, and clinical therapeutics should focus more on relevant metabolic indices

Table_1_Elevated serum uric acid is associated with cognitive improvement in older American adults: A large, population-based-analysis of the NHANES database.docx

BackgroundThe many studies revealing a connection between serum uric acid (SUA) and dementia have reported conflicting results. This study sought to investigate the relations between SUA and cognitive function in older adults.Materials and methodsThe sample was 2,767 American adults aged ≥60 years from the National Health and Nutrition Examination Survey 2011–2014. Cognitive performance was evaluated by the Consortium to Establish a Registry for Alzheimer’s Disease test, animal fluency test, digit symbol substitution test, and composite z-score. Multivariate linear regression analyses were conducted to estimate the association between SUA and cognitive function.ResultsSUA level and cognitive function were significantly, positively correlated. Age significantly correlated with the association between SUA and cognitive function.ConclusionThese findings support a connection between SUA and cognition, showing a positive link between SUA and cognitive scores among older American adults. We contend that a slight rise in uric acid within the normal range is advantageous for enhanced cognition. To confirm the precise dose-time-response relation, more tests will be needed.</p

Ligand-induced chirality in asymmetric CdSe/CdS nanostructures: a close look at chiral tadpoles

Ligand-induced chirality in asymmetric CdSe/CdS core–shell nanocrystals (NCs) has been extensively applied in chiral biosensors, regioselective syntheses and assemblies, circularly polarized luminescence (CPL), and chiroptic-based devices due to their excellent physiochemical properties, such as the tunable quantum confinement effects, surface functionality, and chemical stability. Herein, we present CdSe/CdS NCs with various morphologies such as nanoflowers, tadpoles, and dot/rods (DRs) with chirality induced by surface chiral ligands. The observed circular dichroism (CD) and CPL activities are closely associated with the geometrical characteristics of the nanostructures, such as the shell thickness and the aspect ratio of the CdSe/CdS NCs. Furthermore, in situ observations of the growth of tadpoles with a single tail indicate that the CD response is mainly attributed to the CdS shell, which has a maximum tail length of ∼45 nm (approximately λ/10 of the incident light wavelength). On the other hand, the CPL activity is only related to the CdSe core, and the activity benefits from a thin CdS shell with a relatively high photoluminescence quantum yield (QY). Further theoretical models demonstrated the aspect-ratio-dependent g-factor and QY variations in these asymmetric nanostructures. These findings provide insights into not only the asymmetric synthesis of CdSe/CdS NCs, but also the rational design of CdSe/CdS nanostructures with tunable CD and CPL activities

Forest plot of pooled relative risk for one-year OS from eligible studies.

<p>The area of each square represents the weighting, and the positions of each square demonstrate the risk ratio point estimate. Horizontal lines represent 95% confidence interval (CI). M-H = Mantel-Haenszel. Events = patients died from any cause within one year.</p

Correlation of pathological complete response with survival after neoadjuvant chemotherapy in gastric or gastroesophageal junction cancer treated with radical surgery: A meta-analysis

<div><p>Background</p><p>Neoadjuvant chemotherapy before radical gastrectomy is preferred for locally advanced gastric cancer. To avoid the problematic use of pTNM for patients after neoadjuvant chemotherapy, the Union for International Cancer Control (UICC) and the American Joint Committee on Cancer (AJCC) gastric cancer TNM staging system (8th edition) added ypTNM for the first time. But patients achieving pathological complete response were not covered by the new ypTNM staging system. To investigate whether pathological complete response is associated with better outcome in gastric cancer, as was reported in rectal, breast and bladder cancer.</p><p>Methods</p><p>We systematically searched the databases of PubMed, EMBASE, Web of Science and Cochrane Collaboration’s Central register of controlled trials from January 1988 to April 2015 for publications which reported outcomes of patients with and without pathological complete response (pCR) (pT0N0M0) to investigate whether pCR after neoadjuvant chemotherapy in gastric or gastroesophageal junction (GEJ) treated with radical surgery is associated with better survival. The primary outcome was overall survival (OS). The secondary outcome was disease-free survival (DFS). Both were measured with a relative risk (RR). A meta-analysis was performed using the fixed effects model. Forest plots and the Q test was used to evaluate overall heterogeneity for OS and DFS.</p><p>Results</p><p>A total of seven trials, 1143 patients were included and analyzed after neoadjuvant chemotherapy and radical surgery with no other preoperative treatment. The average rate of pCR was 6.74% (range: 3%-15%). The RR of patients who achieved pCR in the primary tumor and lymph nodes is 0.5 (95% confidence interval [CI], 0.25–0.98; p = 0.04), 0.34 (95% CI, 0.21–0.55; p<0.0001) and 0.44 (95% CI, 0.30–0.63; p<0.0001) for one-year-OS, three-year-OS and five-year-OS, respectively. The summary RR for three-year-DFS was 0.43 (95% CI, 0.25–0.72; p = 0.002).</p><p>Conclusion</p><p>Patients with resectable gastric or GEJ cancer who achieved pCR after neoadjuvant chemotherapy can gain a better outcome than patients without pCR.</p></div