Association between whole blood essential trace elements and cognitive function in older adults.

BACKGROUND: Essential trace elements (ETEs) are essential nutrients for keeping the nervous system functioning. Associations between ETEs and cognitive function are still inconclusive and limited. OBJECTIVES: We aimed to investigate the individual and joint associations between ETEs and cognitive function among older adults. METHODS: A population (N = 2181) at an average age≥ 65 from Yiwu cohort in China was available for this study. Whole blood chromium (Cr), selenium (Se), manganese (Mn), and copper (Cu) concentrations were measured by inductively coupled plasma mass spectrometry (ICP-MS). Cognitive function was assessed using the Mini-Mental State Examination (MMSE), consisting of five specific cognitive domains: orientation, registry, attention and calculation, recall, and language and praxis. Linear regression, restricted cubic spline (RCS) analysis, and Bayesian kernel machine regression (BKMR) were used to analyze the individual and joint associations between ETEs and cognitive function. RESULTS: The association between Cr and MMSE score presented an inverted-U shape (Q3 versus Q1: ß = 0.774, 95 % CI: 0.297, 1.250; Q4 versus Q1: ß = 0.481, 95 % CI: 0.006, 0.956); and Cr was especially associated with the registry, recall, and language and praxis. Per IQR (36.32 µg/L) increase of Se was positively associated with the MMSE score (ß = 0.497, 95 % CI: 0.277, 0.717) and all five cognitive domains. The BKMR showed that the dose-response association between Se and cognitive function increased initially and then decreased with increasing Se concentration when fixed the other ETEs in median. ETEs mixture was positively associated with cognitive function, and Se (posterior inclusion probabilities, PIPs = 0.915) was the most important contributor within the ETEs mixture. CONCLUSIONS: The nonlinear association between Cr and cognitive function suggested further exploration of an appropriate concentration range for ETEs. A positive association between mixed ETEs and cognitive function is a reminder that their joint association should be considered. Further prospective studies or intervention studies are warranted to validate our findings in the future.

Association between type of drinking water and upper gastrointestinal cancer incidence in the Linxian General Population.

BACKGROUND: This study aimed to explore the association between drinking water source and risk of upper gastrointestinal (UGI) cancer, including esophageal cancer (EC) and gastric cancer (GC), in the Linxian General Population Nutrition Intervention Trial (NIT) cohort. METHODS: In this study, we used data from the Linxian NIT cohort, which included 29,584 healthy adults aged 40 to 69 years. Subjects were enrolled in April 1986 and followed up until March 2016. Tap water drinking status and demographic characteristics were collected at baseline. Subjects who drank tap water were treated as the exposed group. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) were estimated using the Cox proportional hazard model. RESULTS: A total of 5,463 cases of UGI cancer were identified during the 30-year follow-up period. After adjusting for multiple factors, the incidence rate of UGI cancer in participants who drank tap water was significantly lower compared with individuals in the control (HR = 0.91, 95% CI: 0.86-0.97). A similar association was observed between tap water drinking and EC incidence (HR = 0.89, 95% CI: 0.82-0.97). The association between drinking tap water and risk of UGI cancer and EC incidence did not vary across the subgroup by age and gender (All Pinteraction > 0.05). For EC incidence, an interaction effect was observed for riboflavin/niacin supplements and drinking water source (Pinteraction = 0.03). No association was observed between drinking water source and GC incidence. CONCLUSIONS: In this prospective cohort study in Linxian, participants who drank tap water had a lower risk of EC incidence. As a source of drinking water, use of tap water may reduce the risk of EC by avoiding exposure to nitrate/nitrite. Measures should be taken to improve the quality of drinking water in high-incidence areas of EC. TRIAL REGISTRATION: The trial is registered with ClinicalTrials.gov (NCT00342654, 21/06/2006), and the trial name is Nutrition Intervention Trials in Linxian Follow-up Study.

Mortality after multivitamin supplementation: Nearly 35-year follow-up of the randomized Linxian Dysplasia Nutrition Intervention Trial.

BACKGROUND: The objective of this study was to update the association between multivitamin supplementation and total or cause-specific mortality in a population with a high prevalence of undernutrition in China. METHODS: The Linxian Dysplasia Nutrition Intervention Trial was a randomized, double-blind, placebo-controlled trial in which 3318 persons aged 40-69 years with esophageal squamous dysplasia were assigned to receive daily multivitamin supplementation or a placebo for 6 years and were followed for 29 years. The primary outcome was esophageal/gastric cardia cancer mortality. The data were analyzed with Cox proportional hazards regression models. Subgroup analyses were performed by common characteristics such as age and gender. RESULTS: The cumulative total mortality was 83.5%. Multivitamin supplementation did not affect total or cause-specific mortality in the participants as a whole (hazard ratio [HR], 0.96; 95% confidence interval [CI], 0.89-1.03). Subgroup analyses showed that no association between multivitamin supplementation and all-cause mortality was observed in men (HR, 0.90; 95% CI, 0.81-1.01), women (HR, 1.01; 95% CI, 0.91-1.12), younger participants (HR, 0.97; 95% CI, 0.87-1.08), or older participants (HR, 0.94; 95% CI, 0.85-1.04). Significant reductions in heart disease mortality (HR, 0.64; 95% CI, 0.47-0.87) and cerebrovascular disease mortality (HR, 0.74; 95% CI, 0.56-1.00) were seen in older men. In a subgroup of younger men and a subgroup of moderate or severe dysplasia, subjects receiving multivitamin supplementation had a lower risk of esophageal/cardia cancer mortality (HR for younger men, 0.76; 95% CI, 0.58-0.99; HR for moderate or severe dysplasia, 0.76; 95% CI, 0.58-1.00). No association between multivitamin supplementation and any cause-specific mortality was observed in a mild dysplasia population. CONCLUSIONS: Multivitamin supplementation in a population with esophageal squamous dysplasia was not associated with the risk of total mortality in the 35-year follow-up of this randomized controlled trial. In light of this and previous trials, multivitamin supplements should be used thoughtfully to improve health status of populations with esophageal squamous dysplasia. LAY SUMMARY: Multivitamin supplementation is common, yet its effect on mortality is unclear. The aim of this study was to update the long-term effects of multivitamin supplementation on total and cause-specific mortality during nearly 35 years of follow-up in the Linxian Dysplasia Nutrition Intervention Trial in China. Multivitamin supplementation in a population with esophageal squamous dysplasia was not associated with the risk of total mortality in the 35-year follow-up of this randomized controlled trial, and this indicates that multivitamin supplements should be used thoughtfully to improve health status.

Helianthus Annuus L. Alleviates High-Fat Diet Induced Atherosclerosis by Regulating Intestinal Microbiota, Inhibiting Inflammation and Restraining Oxidative Stress.

Helianthus Annuus L. (HAL) is composed of flavonoids and polysaccharides. Flavonoids have demonstrated beneficial effects on atherosclerosis (AS). The objective of this study was to investigate the anti-atherosclerosis effect and the related mechanism of HAL. In this study, the AS model induced by high-fat diet (HFD) mice that lacked apolipoprotein E (Apoe[Formula: see text] received feed containing 5% HAL for 24 weeks. After administration, the analysis of plaque on aorta was conducted, and the possible mechanisms were further explored. With HAL treatment, the size of atherosclerotic lesions in HFD-induced AS model mice was reduced. HAL ameliorated dyslipidemia and decreased the combined ratio. HAL up-regulated concentrations of superoxide dismutase (SOD), nitric oxide (NO) and glutathione peroxidase (GSH-Px) and down-regulated concentrations of malondialdehyde (MDA) in the aorta. In addition, 16S rRNA analysis showed that HAL also reduced diversity of the intestinal microbiota, decreased the Firmicutes-to-Bacteroidetes ratio, and increased the relative abundance of probiotics such as Akkermansia muciniphila and Lactobacillus. In the end, HAL decreased the permeability of intestine by increasing the levels of occludin and tight junction protein 1 (ZO-1) in the colon, consequently decreasing concentration of interleukin (IL)-6, IL-1[Formula: see text] and tumor necrosis factor-alpha (TNF-[Formula: see text] in serum and mRNA expressions in the aorta. Data showed that HAL alleviates AS by restraining oxidative stress, regulating intestinal microbiota, decreasing intestinal permeability and inhibiting inflammation. Our findings provided novel insights into the role and mechanism of anti-atherogenic potential of HAL.

Synthesis and biological evaluation of panaxatriol derivatives against myocardial ischemia/reperfusion injury in the rat.

Panaxatriol (PT) is a natural product derived from ginseng that possesses cardioprotective effects in isolated rat hearts. To develop more potent therapeutic agents against myocardial ischemia/reperfusion (MI/R) injury from natural products, a novel series of heterocycle ring-fused panaxatriol derivatives were designed and synthesized. In vitro results showed that approximately half of them exhibited increased cytoprotective activity compared with PT in a cardiomyocyte model of oxygen-glucose deprivation and reperfusion (OGD/R) injury. Furthermore, the in vitro activity of the representative derivative, compound 18, was also confirmed in a rat model of MI/R injury. In vivo results showed that 18 can markedly reduce myocardial infarction size, decrease circulating cardiac troponin I (cTnI) leakage, and alleviate cardiac tissue damage in the rats. Therefore, these findings provide the basis for further development of novel anti-MI/R injury agents.

[Acupuncture combined with cranial electrotherapy stimulation on generalized anxiety disorder: a randomized controlled trial].

OBJECTIVE: To observe the therapeutic effect of acupuncture combined with cranial electrotherapy stimulation (CES) on generalized anxiety disorder (GAD). METHODS: A total of 200 patients with GAD were randomized into an acupuncture+CES group, an acupuncture group, a CES group and a medication group, 50 cases in each one. In the medication group, patients were treated with tandospirone citrate tablet orally, 10 mg after breakfast, lunch and dinner respectively. In the CES group, CES was adopted by SCS brain electromedical instrument, 60 min each time, once a day. In the acupuncture group, acupuncture was applied to Baihui (GV 20), Sishencong (EX-HN 1), Yintang (GV 29), Shenting (GV 24), etc., 30 min each time, once a day. In the acupuncture+CES group, CES was adopted before acupuncture. Treatment of sixty days was required in the 4 groups. Before and after treatment, the scores of Hamilton anxiety scale (HAMA), World Health Organization's quality of life questionnaire-brief version (WHOQOL-BREF) and treatment emergent symptom scale (TESS) were observed, the clinical effect was evaluated, and the relapse of anxiety during follow-up of 1 year after treatment was recorded in the 4 groups. RESULTS: Compared before treatment, the scores of HAMA after treatment were decreased (P<0.05), the scores of WHOQOL- BREF after treatment were increased in the 4 groups (P<0.05), and the improvements of above scores in the acupuncture+CES group were greater than the other 3 groups (P<0.05). The score of TESS after treatment and the relapse rate of 1-year follow-up in the medication group were higher than those in the other 3 groups (P<0.05). The total effective rate in the acupuncture+CES group were superior to the other 3 groups (P<0.05). CONCLUSION: Acupuncture combined with CES can effectively relieve the symptoms in patients with GAD, improve the quality of life, reduce the occurrence of adverse reactions and the relapse rate, and its clinical effect is obviously superior to the western medication, the simple application of acupuncture or CES.

Shank3-deficient thalamocortical neurons show HCN channelopathy and alterations in intrinsic electrical properties.

KEY POINTS: Shank3 increases the HCN channel surface expression in heterologous expression systems. Shank3Δ13-16 deficiency causes significant reduction in HCN2 expression and Ih current amplitude in thalamocortical (TC) neurons. Shank3Δ13-16 - but not Shank3Δ4-9 -deficient TC neurons share changes in basic electrical properties which are comparable to those of HCN2-/- TC neurons. HCN channelopathy may critically mediate events downstream from Shank3 deficiency. ABSTRACT: SHANK3 is a scaffolding protein that is highly enriched in excitatory synapses. Mutations in the SHANK3 gene have been linked to neuropsychiatric disorders especially the autism spectrum disorders. SHANK3 deficiency is known to cause impairments in synaptic transmission, but its effects on basic neuronal electrical properties that are more localized to the soma and proximal dendrites remain unclear. Here we confirmed that in heterologous expression systems two different mouse Shank3 isoforms, Shank3A and Shank3C, significantly increase the surface expression of the mouse hyperpolarization-activated, cyclic-nucleotide-gated (HCN) channel. In Shank3Δ13-16 knockout mice, which lack exons 13-16 in the Shank3 gene (both Shank3A and Shank3C are removed) and display a severe behavioural phenotype, the expression of HCN2 is reduced to an undetectable level. The thalamocortical (TC) neurons from the ventrobasal (VB) complex of Shank3Δ13-16 mice demonstrate reduced Ih current amplitude and correspondingly increased input resistance, negatively shifted resting membrane potential, and abnormal spike firing in both tonic and burst modes. Impressively, these changes closely resemble those of HCN2-/- TC neurons but not of the TC neurons from Shank3Δ4-9 mice, which lack exons 4-9 in the Shank3 gene (Shank3C still exists) and demonstrate moderate behavioural phenotypes. Additionally, Shank3 deficiency increases the ratio of excitatory/inhibitory balance in VB neurons but has a limited impact on the electrical properties of connected thalamic reticular (RTN) neurons. These results provide new understanding about the role of HCN channelopathy in mediating detrimental effects downstream from Shank3 deficiency.

Intakes of fish and polyunsaturated fatty acids and mild-to-severe cognitive impairment risks: a dose-response meta-analysis of 21 cohort studies.

BACKGROUND: The intake of fish and polyunsaturated fatty acids (PUFAs) may benefit cognitive function. However, optimal intake recommendations for protection are unknown. OBJECTIVE: We systematically investigated associations between fish and PUFA intake and mild-to-severe cognitive impairment risk. DESIGN: Studies that reported risk estimates for mild cognitive impairment (MCI), cognitive decline, dementia, Alzheimer disease (AD), or Parkinson disease (PD) from fish, total PUFAs, total n-3 (ω-3) PUFAs, or at least one n-3 PUFA were included. Study characteristics and outcomes were extracted. The pooled RR was estimated with the use of a random-effects model meta-analysis. A dose-response analysis was conducted with the use of the 2-stage generalized least-squares trend program. RESULTS: We included 21 studies (181,580 participants) with 4438 cases identified during follow-up periods (2.1-21 y). A 1-serving/wk increment of dietary fish was associated with lower risks of dementia (RR: 0.95; 95% CI: 0.90, 0.99; P = 0.042, I(2) = 63.4%) and AD (RR: 0.93; 95% CI: 0.90, 0.95; P = 0.003, I(2) = 74.8%). Pooled RRs of MCI and PD were 0.71 (95% CI: 0.59, 0.82; P = 0.733, I(2) = 0%) and 0.90 (95% CI: 0.80, 0.99; P = 0.221, I(2) = 33.7%), respectively, for an 8-g/d increment of PUFA intake. As an important source of marine n-3 PUFAs, a 0.1-g/d increment of dietary docosahexaenoic acid (DHA) intake was associated with lower risks of dementia (RR: 0.86; 95% CI: 0.76, 0.96; P < 0.001, I(2) = 92.7%) and AD (RR: 0.63; 95% CI: 0.51, 0.76; P < 0.001, I(2) = 94.5%). Significant curvilinear relations between fish consumption and risk of AD and between total PUFAs and risk of MCI (both P-nonlinearity < 0.001) were observed. CONCLUSIONS: Fishery products are recommended as dietary sources and are associated with lower risk of cognitive impairment. Marine-derived DHA was associated with lower risk of dementia and AD but without a linear dose-response relation.

[Senile insomnia treated with integrated acupuncture and medication therapy: a randomized controlled trial].

OBJECTIVE: To compare the efficacy difference in the treatment of senile insomnia among western, medication, acupuncture and the integrated therapy of acupuncture and western medication. METHODS: Ninety-eight patients of senile insomnia were randomized into a western medication group (30 cases), an acupuncture group (35 cases) and an integrated acupuncture and medication group (35 cases). In the western medication group, estazolam 1mg was prescribed, taken 30 min before going to bed, oryzanol 20 mg, oral administration, three times a day, for 4 weeks totally. In the acupuncture group, the simple acupuncture therapy was applied at Shenmen (HT 7), Sanyinjiao (SP 6), Anmian (Extra), Baihui (GV 20) and Sishencong (EX-HN 1), as well as the supplementary points selected according to the differentiation. The acupuncture treatment was given once a day, 5 treatments a week, for 4 weeks totally. In the integrated acupuncture and medication group, the western medication was combined with acupuncture. The dosage and usage of western medication were same as those in the western medication group; and acupoints in acupuncture treatment were same as those in the acupuncture group. The treatment lasted for 4 weeks in the three groups. Pittsburgh sleep quality index (PSQI) and clinical efficacy were observed before treatment, after 4 weeks' treatment and in 4 weeks after discontinuity of treatment in the three groups. RESULTS: Four weeks after treatment, the clinical curative rates were 3. 3% (1/30), 21. 2% (7/33) and 25. 7% (9/35) in the western medication group, the acupuncture group and the integrated acupuncture and medicines group separately. The total effective rates were 70. 0%(21/30), 93. 9%(31/33) and 97. 1%(34/35) in the three groups separately. The curative rates and the total effective rates in the integrated acupuncture and medication group and the acupuncture group were higher than those in the western medication group separately (all, P<0. 01). PSQI scores after 4 Weeks' treatment were all improved as compared with those before treatment in the three groups (all P<0. 05). PSQI score in either the integrated acupuncture and medication group or the acupuncture group was lower than that in the western medication group, indicating the significant difference (both P< 0. 05). Four weeks after discontinuity of treatment, the efficacy was stable in the acupuncture group and the integrated acupuncture and medication group. PSQI score did not change as compared with that in the 4th week of treatment. The score in the western medication group ran back, close to that before treatment (P>0. 05). During the treatment, a few patients had dry mouth in the western medication group. The adverse reactions were not discovered in the other two groups. CONCLUSION: The integrated therapy of acupuncture and medication achieves the quick efficacy on senile insomnia and rapidly relieves the symptoms, with quite high clinical curative rate and total effective rate obtained. The long-term efficacy is better than that of western medication. The integrated therapy is the first option among the three therapeutic programs.

Application of random forests to select premium quality vegetable oils by their fatty acid composition.

In order to discriminate premium quality from inexpensive edible oils, the fatty acid profiles of tea, rapeseed, corn, sunflower and sesame oil were compared with the ones from extra virgin olive oil (EVOO). Fatty acid methyl esters were quantified by GC/MS. Principal component analysis (PCA) and random forests (RF) were applied to cluster the samples. RF showed a better ability of discrimination and also revealed the contribution of each variable to the clustering model. The multidimensional scaling (MDS) plot of the RF proximity matrix demonstrated that tea oil was similar to EVOO. Meanwhile, it was observed that the total content of cis-monounsaturated fatty acids (79.48%) in tea oil was close to EVOO (80.71%), especially the oleic acid (77.38% and 77.45%, respectively). The results suggest that tea oil might be a good edible oil choice, considering the high oleic acid content and similar fatty acid profiles compared to those of EVOO.

[Ru/AC catalyzed ozonation of recalcitrant organic compounds].

Ozonation and Ru/AC catalyzed ozonation of dimethyl phthalate (DMP), phenols and disinfection by-products precursors were studied. It shows that Ru/AC catalyst can obviously enhance the mineralization of organic compounds. In the degradation of DMP, TOC removal was 28.84% by ozonation alone while it was 66.13% by catalytic ozonation. In the oxidation of 23 kinds of phenols, TOC removals were 9.57%-56.08% by ozonation alone while they were 41.81%-82.32% by catalytic ozonation. Compared to ozonation alone, Ru/AC catalyzed ozonation was more effective for the reduction of disinfection by-products formation potentials in source water. The reduction of haloacetic acids formation potentials was more obvious than thichlomethane formation potentials. After the treatment by catalytic ozonation, the haloacetic acids formation potentials decreased from 144.02 microg/L to 58.50 microg/L, which was below the standard value of EPA. However ozonation alone could not make it reach the standard. The treatments of source water by BAC, O3 + BAC, O3/AC + BAC and Ru/AC + O3 + BAC were also studied. In the four processes, TOC removal was 3.80%, 20.14%, 27.45% and 48.30% respectively, COD removal was 4.37%, 27.22%, 39.91% and 50.00% respectively, UV254 removal was 8.16%, 62.24%, 67.03% and 84.95% respectively. Ru/AC + O3 + BAC process is more effective than the other processes for the removal of TOC, COD and UV254 and no ruthenium leaching observed in the solution. It is a promising process for the treatment of micro polluted source water.

Catalytic ozonation of dimethyl phthalate and chlorination disinfection by-product precursors over Ru/AC.

Catalytic ozonation of dimethyl phthalate (DMP) in aqueous solution (5mg/L) under various reactions was performed to examine the effect of catalyst dosage, catalyst particle size, ozone dosage, and gas flow rate on the mineralization of DMP. The mineralization of DMP can be achieved via ozonation and the presence of Ru/AC could greatly accelerate the mineralization rate of DMP in ozonation process. In the continuous experiment of the Ru/AC catalyzed ozonation of DMP, total organic carbon (TOC) removals were kept stable around 75% during 42 h reaction. No leaching of ruthenium was observed in the treated water samples. The treatment of natural water using Ru/AC+O(3), Ru/AC+O(2) and ozonation alone was studied. In the Ru/AC+O(3) process, TOC removals, the reductions of the haloacetic acid formation potentials (HAAFPs), and the reductions of the trihalomethane formation potentials (THMFPs) of 11 water samples were 22-44%, 39-61% and 50-65%, respectively. Ru/AC+O(3) process was much more effective than ozonation alone for TOC removal and the reduction of disinfection by-product formation potential (DBPFP) in the treatment of natural water. It is a promising water treatment technology.