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Background: Recent findings suggest a possible role of diet, particularly nutrient intakes and dietary patterns, in the prevalence of mild cognitive impairment (MCI); few studies, however, have been explicitly devoted to the relationship between dietary habits and MCI. Objectives: We aimed to explore the association between dietary habits, including meal timing, and MCI among older Chinese adults. Methods: This cross-sectional study involved data collected at the baseline of the Tianjin Elderly Nutrition and Cognition Cohort (TENCC) study, in which 3,111 community-dwelling older adults (326 MCI patients and 2,785 non-MCIs) from a rural area of Tianjin, China, were recruited. In March 2018 to June 2019, all participants underwent a detailed neuropsychological evaluation that allowed for psychometric MCI classification. Information on self-reported dietary behaviors was gathered via face-to-face interviews. Crude and multivariable-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using logistic regression models. Results: In the multivariable-adjusted models, eating breakfast 4 to 6 times per week (vs. ≤3 times per week, OR: 0.45; 95% CI: 0.26, 0.75), drinking water before breakfast (yes vs. no, OR: 0.64; 95% CI: 0.51, 0.82), consuming water ≥1.5L per day (vs. Conclusion : This study suggests that dietary habits, including breakfast frequency, daily water consumption, cooking oil consumption, and meal timing, may be associated with the risk of MCI. If replicated, these findings would open new possibilities of dietary interventions for MCI.

With an aging population, late-life depression has been a major health problem in rural China. This study aims to explore the gender-specific prevalence of geriatric depression in rural Tianjin, its influencing factors, and to provide a scientific basis for the prevention and intervention of depression in the elderly.A cross-sectional study of 4,933 elderly individuals in rural Tianjin was conducted using the cluster sampling method. The independent samples t-test and chi-squared test were used to assess differences in participants' characteristics by depressive symptoms, while multiple linear regressions and multiple logistic regressions were used to analyze the potential influencing factors of depression.The prevalence of geriatric depression was found to be 12.2% in the study participants (9.5% in men and 14.5% in women). Gender, education, household income, employment, living alone, social activities, physical exercise and chronic diseases were associated with depression (P0.05). In addition to the above factors, sleep duration was also related with scores on self-rating depression scale (P0.05).The study used a cross-sectional approach, so causation cannot be concluded.Late-life depression is a serious mental health issue in rural China, highlighting the importance of appropriate diagnosis and treatment as a priority to improve the quality of mental health.

Background: Handgrip strength (HGS) and serum folate and homocysteine (Hcy) levels were associated with cognitive function. However, little was known whether there were interactions between HGS and serum folate and Hcy levels on cognitive function. Objective: To examine the interactions between HGS and serum folate and Hcy levels on cognitive function. Methods: This study analyzed the baseline data of the Tianjin Elderly Nutrition and Cognition Cohort study. All participants aged ≥60 years were potential eligible. HGS was measured using a grip strength dynamometer. Serum folate and Hcy levels were assayed using standard laboratory protocol. A Mini-Mental State Examination was used to assess cognitive function. Linear regressions were employed to examine the interactions between HGS and serum folate and Hcy levels on cognitive function. Results: 4,484 participants were included in this study. There were interactions between HGS and serum folate and Hcy levels on cognitive function. Furthermore, subjects with strong HGS and sufficient folate level had the best cognitive function (β= 2.018), sequentially followed by those with strong HGS and insufficient folate level (β= 1.698) and with poor HGS and sufficient folate level (β= 0.873). Similarly, cognitive function was ranked in the descending order of subjects with strong HGS and normal Hcy level (β= 1.971), strong HGS and high Hcy level (β= 1.467), and poor HGS and normal Hcy level (β= 0.657). Conclusion: There were interactions between HGS and serum folate and Hcy levels on cognitive function. However, the temporal associations cannot be examined in a cross-sectional study. Further cohort study should be conducted to confirm these associations in the future.

Marital status may have an impact on the elderly population's health, but few studies in China discussed about the association between marital status and cognitive impairment.To investigate the relationship between marital status and cognitive impairment. To compare the influences of marital status on dementia between men and women.This study was based on a representative national cross-sectional epidemiological survey in China. We randomly selected 13 provinces and municipalities and included 19,276 participants aged 65 years or older in our study. Data was collected by interviewing the participants about their sociodemographic characteristics, and neuropsychological testing was administered to the participants by neurologists. To analyze the association between marital status and cognitive impairment, multiple logistic regression was based on a series of models.Among the 19,276 subjects, about 77.2% were married, 1.6% were single, 21.2% were divorced/separated or widowed. The odds ratios (OR) of dementia were higher in single (OR: 2.13, CI: 1.53-2.97; p 0.001), divorced/separated/widowed when they were ≤55 years old (OR: 1.75, CI: 1.30-2.35; p 0.001), and divorced/separated/widowed when they were55 years old (OR: 1.16, CI: 1.03-1.31; p 0.001) participants than in married ones. Divorced/separated/widowed ≤55 men had about 2.75 times increase in dementia risk than married men.People with long-term divorced/separated/widowed status would be associated to cognitive impairment more than those with short-term divorced/separated/widowed status. Men may be affected by marriage disruption more than women in terms of increasing the risk of dementia.

The occurrence of telomere attrition in brain may cause senescence and death of neurons, leading to cognitive decline. Folic acid (FA) has been reported to improve cognitive performance in mild cognitive impairment; however, its association with telomere remains unclear. The study aimed to investigate if alleviation of telomere attrition by FA supplementation could act as a potential mechanism to delay age-related cognitive decline in senescence-accelerated mouse prone 8 (SAMP8). Aged SAMP8 mice were assigned to four treatment groups: FAdeficient diet (FA-D) group, FA-normal diet (FA-N) group, low FA-supplemented diet (FA-L) group and high FAsupplemented diet (FA-H) group. There was also an age-matched senescence-accelerated mouse resistant 1 (SAMR1) control group (Con-R), and a young SAMP8 control group (Con-Y). The results demonstrated that FA supplementation delayed age-related cognitive decline and neurodegeneration in SAMP8 mice. Importantly, this effect could be attributed to the alleviated telomere attrition, which might be interpreted by the decreased levels of reactive oxygen species. Additionally, improved telomere integrity stimulated mitochondrial function via telomere-p53-mithondria pathway, consequently delayed neuronal degeneration. In conclusion, we demonstrate that FA supplementation delays age-related neurodegeneration and cognitive decline in SAMP8 mice, in which alleviated telomere attrition could serve as one influential factor in the process.

Background: Folate and vitamin B12 are well-known as essential nutrients that play key roles in the normal functions of the brain. Inflammatory processes play at least some role in the pathology of AD. Effective nutritional intervention approaches for improving cognitive deficits that reduce the peripheral inflammatory cytokine levels have garnered special attention. Objective: The present study aimed to determine whether supplementation with folic acid and vitamin B12, alone and in combination improves cognitive performance via reducing levels of peripheral inflammatory cytokines. Methods: 240 participants with MCI were randomly assigned in equal proportion to four treatment groups: folic acid alone, vitamin B12 alone, folic acid plus vitamin B12 or control without treatment daily for 6 months. Cognition was measured with WAIS-RC. The levels of inflammatory cytokines were measured using ELISA. Changes in cognitive function or blood biomarkers were analyzed by repeatedmeasure analysis of variance or mixed-effects models. This trial has been registered with trial number ChiCTR-ROC-16008305. Results: Compared with control group, the folic acid plus vitamin B12 group had significantly greater improvements in serum folate, homocysteine, vitamin B12 and IL-6, TNF-α, MCP-1. The folic acid plus vitamin B12 supplementation significantly changed the Full Scale IQ (effect size d = 0.169; P = 0.024), verbal IQ (effect size d = 0.146; P = 0.033), Information (d = 0.172; P = 0.019) and Digit Span (d = 0.187; P = 0.009) scores. Post hoc Turkey tests found that folic acid and vitamin B12 supplementation was significantly more effective than folic acid alone for all endpoints. Conclusions: The combination of oral folic acid plus vitamin B12 in MCI elderly for six months can significantly improve cognitive performance and reduce the levels of inflammatory cytokines in human peripheral blood. The combination of folic acid and vitamin B12 was significantly superior to either folic acid or vitamin B12 alone.

Background The nutrition state plays an important role in the progress of aging. Folate may play a role in protecting mitochondrial (mt) DNA by reducing oxidative stress. Objective The primary aim of this study was to examine the association of mitochondrial oxidative damage with risk of Alzheimer's disease (AD), and to explore the possible role of folate metabolites in this association in a matched case-control study. Methods Serum folate metabolites and mitochondrial function in peripheral blood cells were determined in 82 AD cases and 82 healthy controls, individually matched by age, gender, and education. Results AD patients had lower serum levels of folate and higher homocysteine (Hcy) concentration. AD patients had a reduced mtDNA copy number, higher mtDNA deletions, and increased 8-OHdG content in mtDNA indicative of reduced mitochondrial function. The highest level of mtDNA copy number would decrease the risk of AD (OR = 0.157, 95% CI: 0.058-0.422) compared to the lowest level, independently of serum folate, and Hcy levels. Serum folate levels correlated with low 8-OHdG content in mtDNA both in AD patients and controls, independently of serum Hcy level. Moreover, serum Hcy levels correlated with low copy number in mtDNA both in AD patients and controls, independently of serum folate levels. Conclusion In conclusion, mitochondrial function in peripheral blood cells could be associated with risk of AD independent of multiple covariates. AD patients with a folate deficiency or hyperhomocysteinemia had low mitochondrial function in peripheral blood cells. However, further randomized controlled trials are need to determine a causal effect.

To examine the association between blood cholesterol concentrations and Alzheimer's disease (AD) in the Chinese elderly. A case-control study was implemented between November 2011 and November 2017. Elderly patients aged ≥ 55 years with (n = 117) and without AD (control participants; n = 117) were recruited from the Neurology Central Hospital of Tianjin, China. The associations between AD and blood parameters were assessed using multiple binary logistic regression analyses adjusted for multiple covariates. Higher serum total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels and lower serum high-density lipoprotein cholesterol (HDL-C) levels associated with AD risk in the models adjusted for (1) age, sex and education; and (2) further adjusted for body mass index, smoking status, stroke, hypertension, type 2 diabetes mellitus and heart disease. Increased serum TC and LDL-C levels and lower HDL-C levels were independently associated with the risk of AD.

Background: Leukocyte telomere length (LTL) is associated with the aging process and age-related degenerative diseases. The relation of peripheral blood LTL to mild cognitive impairment (MCI) and Alzheimer’s disease (AD) and the role of folate and homocysteine (Hcy) in this relation remain unclear. Objectives: We aimed to investigate the association between LTL and the risks of MCI/AD, and to explore whether folate and Hcy may play a role in this association. Methods: This case-control study included 129 MCI subjects, 131 AD patients and 134 healthy controls. LTL was assessed using real-time polymerase chain reaction assay. Serum folate levels were tested by chemiluminescence enzyme immunoassay, and serum Hcy levels were measured using the enzymatic cycling method. Data were analyzed using multivariate logistic regression and multivariable linear regression with adjustment for potential confounders. Results: The mean LTL was 1.56 ± 0.25 in controls, 1.44 ± 0.23 in MCI, and 1.28 ± 0.28 in AD patients (p< 0.01). In multivariate logistic regression, subjects in the longest LTL tertile had lower OR for MCI (OR 0.246; 95% CI 0.101–0.597) and AD (OR 0.123; 95% CI 0.044–0.345) in comparison to subjects in the shortest tertile. Shorter LTL was dose-dependently related to the ORs of MCI and AD. Further, serum folate concentration was positively associated with LTL (p < 0.01), while serum Hcy level was negatively associated with LTL (p < 0.05). In stratified analyses, LTL-MCI/AD association varied by serum folate and Hcy level. Conclusions: Shorter LTL is associated with the risks of MCI/AD. Folate and Hcy might play an important role in this association.

BACKGROUND The neuroprotective benefits of combined folic acid and docosahexaenoic acid (DHA) on cognitive function in mild cognitive impairment (MCI) patients are suggested but unconfirmed. OBJECTIVE To explore the effects of 6-month folic acid + DHA on cognitive function in patients with MCI. METHODS Our randomized controlled trial (trial number ChiCTR-IOR-16008351) was conducted in Tianjin, China. We divided 160 MCI patients aged > 60 years into four regimen groups randomly: folic acid (0.8 mg/day) + DHA (800 mg/day), folic acid (0.8 mg/day), DHA (800 mg/day), and placebo, for 6 months. Cognitive function and blood amyloid-β peptide (Aβ) biomarker levels were measured at baseline and 6 months. Cognitive function was also measured at 12 months. RESULTS A total of 138 patients completed this trial. Folic acid improved the full-scale intelligence quotient (FSIQ), arithmetic, and picture complement scores; DHA improved the FSIQ, information, arithmetic, and digit span scores; folic acid + DHA improved the arithmetic (difference 1.67, 95% CI 1.02 to 2.31) and digital span (1.33, 0.24 to 2.43) scores compared to placebo. At 12 months, all scores declined in the intervention groups. Folic acid and folic acid + DHA increased blood folate (folic acid + DHA: 7.70, 3.81 to 11.59) and S-adenosylmethionine (23.93, 1.86 to 46.00) levels and reduced homocysteine levels (-6.51, -10.57 to -2.45) compared to placebo. DHA lower the Aβ40 levels (-40.57, -79.79 to -1.35) compared to placebo (p

To explore the demographic characteristics and main types of memory impairment in the Memory Clinic of China and to provide references for future research. Demographic, cognitive, and etiological data of 2,742 cognitive impairment (CI) patients who were in the Memory Clinic at Tianjin Huanhu Hospital from January 2011 to October 2018 were analyzed. The main subtypes of CI were AD (38.33%), MCI (19.55%), VaD (8.57%), FTLD (7.37%) and DLB/PDD (5.91%). The mean age was 68.5 ± 9.97, with 82.13% older than 60 years. There were slightly more females (50.58%) than males (49.42%). There were a relatively equal number of patients who were educated less than (55.12%) and more than nine years (44.88%). Most patients (82.91%) were married and only 23.63% patients had a family history of CI. CI occurred primarily in the elderly, namely those who were between 60 and 79 years old. More than half of those with AD, DLB, PDD, and FTLD were categorized at mild or moderate levels. The bvFTD (n = 127, 62.9%) was the primary subtype of FTLD. Standardized diagnostic procedures, detailed neuropsychological assessments, molecular biology tests, and follow-ups are important for the early diagnosis and treatment of cognitive impairment diseases.

Embryonic development is a critical period wherein brain neurons are generated and organized. Maternal dietary folate, a cofactor in one-carbon metabolism, modulates neurogenesis and apoptosis in foetal brain neurons. We hypothesized that aberrant neuronal apoptosis may affect the development of the central nervous system during maternal folic acid deficiency, with evident effects because maternal folic acid deficiency modulates the microRNA-34a associated with Bcl-2 pathway during embryonic development. Four-week-old female Sprague-Dawley rats were divided randomly into two groups (10 rats per group): a folate-deficient diet group and a folate-normal diet group. The diets were administered to the rats 60 d before mating, which was continued for the pregnant dams until parturition. Maternal folic acid deficiency increased neuronal apoptosis in the hippocampus and the cortex in the offspring. Furthermore, maternal folic acid deficiency increased the ratio of cleaved caspase-3/caspase-3, followed by an increase in caspase-3 activity. Moreover, maternal folic acid deficiency downregulated Bcl-2 and upregulated Bax, and this effect associate with maternal folic acid deficient increases expression of microRNA-34a. Together, the present results indicate that maternal folic acid deficiency stimulates neuronal apoptosis via microRNA-34a associated with Bcl-2 signalling in rat offspring.

Disturbed deoxythymidine triphosphate biosynthesis due to the inhibition of thymidylate synthase (TS) can lead to uracil accumulation in DNA, eventually, lead to neurocytes apoptosis and cognitive decline. Folic acid supplementation delayed cognitive decline and neurodegeneration in senescence-accelerated mouse prone 8 (SAMP8). Whether folic acid, one of nutrition factor, the effect on the expression of TS is unknown. The study aimed to determine if folic acid supplementation could alleviate age-related cognitive decline and apoptosis of neurocytes by increasing TS expression in SAMP8 mice. According to folic acid concentration in diet, four-month-old male SAMP8 mice were randomly divided into three different diet groups by baseline body weight in equal numbers. Moreover, to evaluate the role of TS, a TS inhibitor was injected intraperitoneal. Cognitive test, apoptosis rates of neurocytes, expression of TS, relative uracil level in telomere, and telomere length in brain tissue were detected. The results showed that folic acid supplementation decreased deoxyuridine monophosphate accumulation, uracil misincorporation in telomere, alleviated telomere length shorting, increased expression of TS, then decreased apoptosis rates of neurocytes, and alleviated cognitive performance in SAMP8 mice. Moreover, at the same concentration of folic acid, TS inhibitor raltitrexed increased deoxyuridine monophosphate accumulation, uracil misincorporation in telomere, and exacerbated telomere length shorting, decreased expression of TS, then increased apoptosis rates of neurocytes, and decreased cognitive performance in SAMP8 mice. In conclusion, folic acid supplementation alleviated age-related cognitive decline and inhibited apoptosis of neurocytes by increasing TS expression in SAMP8 mice.

Maternal folate status during pregnancy may influence central nervous system (CNS) development in offspring. However, the recommended intakes of folic acid for women of childbearing age differ among countries and there is still no consensus about whether folic acid should be supplemented continuously throughout pregnancy. We hypothesized that folic acid supplementation may be more beneficial for offspring's neurobehavioral development if prolonged throughout pregnancy instead of being limited to the periconceptional period. In this study, three groups of the female rats were fed folate-normal, folate-deficient, or folate-supplemented diets throughout pregnancy. In another group, the female rats were fed folate-supplemented diet from mating for 10 consecutive days and then fed folate-normal diet for remainder days of pregnancy. The results showed that maternal folate deficiency increased plasma homocysteine (Hcy) concentration in dams, delayed early sensory-motor reflex development, impaired spatial learning and memory ability, and caused ultrastructural damages in the hippocampus of offspring. Maternal folic acid supplementation would be more effective on improving early sensory-motor reflex development and spatial learning and memory ability in offspring if prolonged throughout pregnancy instead of being limited to the periconceptional period. In conclusion, prolonged maternal folic acid supplementation throughout pregnancy would be more effective in neurobehavioral development of offspring in rats.

Aim To comprehensively and exhaustively assess the relationship between serum ferritin levels and incidence of prediabetes in a prospective study. Methods This prospective cohort study ( n =7380) with a mean follow-up of 3.07 years (range: 1–7, 95% CI: 3.03–3.12) was conducted in Tianjin, China. Blood fasting glucose, oral glucose tolerance test, serum ferritin levels and other potentially confounding factors were measured at baseline and at each year of follow-up. Adjusted Cox proportional hazards regression models were used to assess the gender-specific relationship between baseline and mean serum ferritin quintiles and prediabetes. Results The incidence of prediabetes was 85 per 1000 person-years among men and 44 per 1000 person-years among women during follow-up (from 2007 to 2014). After adjusting for potential confounders, hazard ratios (95% CI) for prediabetes across baseline ferritin quintiles were: for men, 1.00, 1.13 (0.90–1.40), 1.20 (0.97–1.48), 1.41 (1.14–1.73) and 1.73 (1.41–2.11); and for women, 1.00, 1.01 (0.74–1.38), 0.68 (0.48–0.96), 0.84 (0.61–1.15) and 1.07 (0.80–1.45), respectively. Similar results were also observed for mean ferritin levels. Conclusion Both baseline and mean serum ferritin levels were significantly and linearly related to prediabetes in men, whereas U-shaped relationships were observed between baseline and mean serum ferritin and prediabetes in women. The relationship between prediabetes risk and mean serum ferritin levels may be more stable than one with baseline serum ferritin levels.

BACKGROUND In this study we investigated changes in the status of antibiotic use in Tianjin since the implementation of the Antibiotic Stewardship Program (ASP) (2011-2013), as well as existing problems, strategies, and outcomes to promote rational clinical antibiotic use. MATERIAL AND METHODS A quasi-experimental study was performed to investigate situations of antibiotic use in secondary and tertiary general hospitals in Tianjin from April 2011 to 2013. Five major indicators were analyzed: percentage of antibiotic use in inpatient cases (%), antibacterial use density (AUD), proportion of prophylactic antibiotic application for type I surgical incision, compliance rate of medication administration 0.5-2.0 h before such procedures, and antibiotic prophylaxis for ≤24 h in patients receiving these surgeries. RESULTS There was a decrease in the percentage of antibiotic use across general hospitals (60.38% to 46.88%), in AUD (51.60% to 35.37%), and in the proportion of prophylactic antibiotic applications for type I incisions (86.67% to 25.08%). For patients undergoing these procedures, there was an increased compliance rate of medication administration of 0.5-2.0 h prior to surgery (86.38% to 100%), and of antibiotic prophylactic use for ≤24 h (40.30% to 96.37%). CONCLUSIONS Implementation of the ASP campaign has reduced irrational antibiotic use, promoted rational antibiotic use, and delayed antibiotic resistance.

Prehypertension is a public health epidemic associated with various adverse outcomes, but can be reversed by timely intervention. However, little attention has been paid to prehypertension. Complement C3 is a central hub of complement-related immune system. We examined the association between C3 and prehypertension in an adult population for the first time, aiming to investigate whether pro-inflammatory immune response is involved in the prehypertensive state. About 7820 Tianjin residents without hypertension were categorized into sex-specific quintiles based on their serum concentration of complement C3. Adjusted logistic regression models were used separately by gender to assess the association between C3 quintiles and the prevalence of prehypertension. After multiple adjustment, the odds ratios (95% confidence interval) for prehypertension across increasing quintiles of C3 were 1.00 (reference), 1.02 (0.84, 1.25), 1.15 (0.94, 1.42), 1.25 (1.01, 1.54), and 1.71 (1.35, 2.17) (p for trend < 0.0001) among men and were 1.00 (reference), 1.17 (0.92, 1.49), 1.13 (0.88, 1.44), 1.15 (0.89, 1.48), and 1.40 (1.07, 1.84) (p for trend = 0.03) among women. The findings suggested that elevated serum C3 levels are associated with prehypertension. Reducing inflammation may be a potential therapeutic strategy for prehypertension and hypertension that is worthy of further studies and discussion.

Background: Mild cognitive impairment (MCI) represents an intermediate and modifiable stage between normal aging and dementia. There is an urgent need for simple, non-invasive testing of MCI by blood biomarkers. Objective: This study aimed to retrospectively evaluate the association of red blood cell (RBC) indices with MCI, and select the best hematologic characteristic for detection of MCI in elderly Chinese. Methods: Matched case-control study was carried out with 85 pairs of MCI subjects and healthy controls. The matching criteria was age, gender and education attainment. All samples were analyzed for RBC indices, including hemoglobin (HGB), hematocrit (HCT), mean corpuscular volume (MCV), mean corpuscular hemoglobin concentration (MCHC) and red cell distribution width-standard deviation (RDW-SD). A conditional logistic regression model was used to evaluate the association between RBC indices and MCI. The diagnostic efficacy of the biomarkers was evaluated by receiver operating characteristics (ROC). Results: Among all RBC indices, there were significant differences in HGB (124.82 ± 7.89 vs. 133.93 ± 4.52, P < 0.001) and RDW-SD (45.29 ± 2.03 vs. 41.34 ± 4.41, P < 0.001) between two groups. In the logistic regression model, after adjustment for lifestyle factors and comorbidities, significant statistically associations have been found between higher HGB and lower risk of MCI (adjusted OR: 0.831; 95% CI: 0.773-0.893), higher RDW-SD and a higher risk of MCI (adjusted OR: 1.575; 95% CI: 1.326- 1.872). ROC analysis suggested that the largest area under the ROC curve (AUC) was found with the combination of HGB and RDW-SD (AUC = 0.842), followed by HGB(AUC = 0.795), and finally by modest RDW-SD (AUC = 0.777). Combination of HGB 43.4 fL yielded a sensitivity of 92% and a specificity of 89%, overall diagnosis efficiency of which were better than HBG and RDW-SD alone. Conclusion: Lower HGB and higher RDW-SD alone were significantly found to be associated with increased risk of MCI, and offered modest sensitivity and specificity as a diagnostic marker. The combination of HGB and RDW-SD was more sensitive and had higher classification accuracy for differentiating MCI from healthy controls. Further prospective research is needed to clarify whether HGB in combination with RDW-SD may be a potential diagnostic tool for early diagnosis of AD.

To explore the association between the levels of serum folate, vitamin B

ObjectivesThis study examined the relationship between environmental correlates and children’s sedentary time (ST), light physical activity (LPA) and moderate-to-vigorous physical activity (MVPA) in preschool children.DesignCross-sectional studySettingA birth cohort in Drenthe, a northern province and relatively rural area of the Netherlands.ParticipantsValid data both for the ActiGraph and the questionnaire were obtained from 505 child–parent pairs.Primary and secondary outcome measuresST, LPA and MVPA of children were objectively measured by ActiGraph accelerometry (minimum three wearing days, more than 10 hours/day). Environmental correlates were collected using a questionnaire reported by parents that included household characteristics, parental and children’s PA behaviours and neighbourhood environment (eg, traffic safety, road network and presence of PA facilities). Potential correlates were identified using linear regression analysis, adjusted by age, gender, siblings, and maternal age and education level. Ordinary least square regression-based path analysis was used to estimate direct and indirect effects on activity outcomes in mediation models.ResultsLinear regression analysis showed that ‘parents taking children to play sports’ was related to less ST, more LPA and MVPA; more outdoor play was also related to less ST and more LPA, but not MVPA. Parents who perceived more PA facilities in their neighbourhood showed more support for ‘taking children to play sports’, and this was associated with less ST or more MVPA compared with children living with less PA facilities in their neighbourhood. No evidence was found for a relation between traffic safety or road network with ST, LPA and MVPA.ConclusionsThis study indicated that parental support and child outdoor play may influence children’s daily PA patterns. Convenient neighbourhood PA facilities, such as parks and playgrounds, had an indirect effect through parental support associated with lower children’s ST and higher MVPA, even in relatively rural areas.

Bone mesenchymal stem cells (MSCs) are an excellent donor graft source due to their potential for self-renewal and multidirectional differentiation. However, it is difficult to obtain high quality MSCs and to induce them to differentiate into neuron-like cells. Fasudil, a Rho kinase inhibitor, exhibits therapeutic potential in spinal cord injuries and stroke. The present study investigated the effect of fasudil on the differentiation of MSCs into neuron-like cells. MSCs were obtained from rat femur marrow, expanded in culture medium, and used at the third passage for subsequent experiments. MSCs were pre-induced with 10 ng/ml basic fibroblast growth factor (bFGF) for 24 h, which was followed by induction with fasudil. A control untreated group and a group treated with fasudil + XAV939, a Wnt/β-catenin pathway inhibitor, were also used in the present study. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR), western blot analysis and immunofluorescence staining were performed in order to detect neuron-specific markers, including neuron-specific enolase (NSE), nestin and neurofilament-M (NF-M). Following induction with fasudil, neuron-like cell morphology was observed. In the fasudil + XAV939 and control groups, no obvious changes in cell shape were observed. The results of RT-qPCR, western blot analysis and immunofluorescence staining indicated that expression of the neuron-specific markers NSE, nestin and NF-M was detected in the fasudil group. The differentiation of MSCs into neuron-like cells induced by fasudil was eliminated when the Wnt/β-catenin pathway was inhibited. The present study demonstrated that fasudil may induce MSCs to differentiate into neuron-like cells, however further studies are required to determine the specific mechanisms involved in the effect of fasudil on the Wnt/β-catenin pathway. In addition, further research is required to examine the functional characteristics of the induced neuron-like cells, in order to establish their suitability for clinical treatments in the future.

The computer/mobile devices usage time (CMD-UT) is closely related to a sedentary lifestyle, which is an important risk factor for non-alcoholic fatty liver disease (NAFLD). But their direct relationship remains unclear.We aimed to examine the relationship between CMD-UT and newly diagnosed non-alcoholic fatty liver disease (NAFLD) in Chinese adults.This cross-sectional study was conducted on 7516 adults in Tianjin, China. The CMD-UT was collected via a questionnaire included five categories. NAFLD [with normal or elevated alanine transaminase (ALT) levels] was diagnosed by at least twice liver ultrasonography examinations and serum ALT concentrations (41 U/L in males and 33 U/L in females).The prevalence of overall NAFLD, NAFLD with normal or elevated ALT levels was 18.2, 14.2, and 4.0%, respectively. After adjustments for potential confounding factors, the odds ratios (95% confidence interval) of having overall NAFLD by increasing CMD-UT levels were 1.00 for 1 h/d, 1.58 (1.22-2.05) for 1-3 h/d, 1.58 (1.18-2.11) for 3-5 h/d, 1.65 (1.21-2.27) for 5-10 h/d, and 1.99 (1.29-3.05) for ≥10h/d (P-trend for CMD-UT levels = 0.02), respectively. Similar relations were observed with the use of NAFLD with normal or elevated ALT levels.The present study is the first to find that CMD-UT levels are independently associated with NAFLD. Key Messages The computer/mobile devices usage time levels are independently associated with the prevalence of non-alcoholic fatty liver disease.

Although the prevalence of prehypertension is rapidly increasing in China, the medical community has paid little attention to its prevention. Prior studies have demonstrated that uric acid directly contributes to vascular remodelling and endothelial dysfunction. However, few prospective studies have assessed the relationship between serum uric acid and prehypertension. We therefore designed a larger-scale cohort study to examine whether uric acid level is a predictive factor for developing prehypertension in adults. Participants were recruited from Tianjin Medical University General Hospital-Health Management Centre. A prospective assessment (n=15 143) was performed. Participants without a history of hypertension or prehypertension were followed up for 2 to 6 years with a median follow-up duration of 2.8 years. Serum uric acid levels and blood pressure were assessed yearly during the follow-up. Adjusted Cox proportional hazards regression models were used to assess relationships between the quintiles of uric acid levels and the incidence of prehypertension. The incidence of prehypertension was 191 per 1000 person-years. In the final multivariate models, the hazard ratios (95% confidence interval) for prehypertension across uric acid quintiles were 1.00 (reference), 0.98 (0.90–1.07), 1.01 (0.93–1.10), 1.09 (1.001–1.20) and 1.17 (1.06–1.29) (P for trend

Background/Aims. Low serum folate levels can alter inflammatory reactions. Both phenomena have been linked to Alzheimer’s disease (AD), but the effect of folic acid on AD itself is unclear. We quantified folate supplementation’s effect on inflammation and cognitive function in patients with AD over the course of 6 months.Methods. Patients newly diagnosed with AD (age > 60 years;n=121; mild to severe; international criteria) and being treated with donepezil were randomly assigned into two groups with (intervention group) or without (control group) supplemental treatment with folic acid (1.25 mg/d) for 6 months. The Mini-Mental State Examination (MMSE) was administered to all patients at baseline and follow-up, and blood samples were taken before and after treatment. We quantified serum folate, amyloid beta (Aβ), interleukin-6 (IL-6), tumor necrosis factorα(TNFα), plasma homocysteine (Hcy), S-adenosylmethionine (SAM), S-adenosylhomocysteine (SAH), and the mRNA levels of presenilin (PS), IL-6, and TNFαin leukocytes. Data were analyzed using a repeated-measures mixed model.Results. The mean MMSE was slightly increased in the intervention group compared to that in the control group (P<0.05). Posttreatment, plasma SAM and SAM/SAH levels were significantly higher (P<0.05), while Aβ40, PS1-mRNA, and TNFα-mRNA levels were lower in the intervention group than in the control group (P<0.05). The Aβ42/Aβ40ratio was also higher in the intervention group (P<0.05).Conclusions. Folic acid is beneficial in patients with AD. Inflammation may play an important role in the interaction between folic acid and AD. This trial is registered with clinical trial registration numberChiCTR-TRC-13003246.

Background/Aims: Our aim was to evaluate whether visceral adiposity index (VAI) could predict the risk of type 2 diabetes (T2D) in different genders and to compare the predictive ability between VAI and other fatness indices. Methods: Four thousand seventy-eight participants including 1,817 men and 2,261 women, aged 18 and older and free of T2D at baseline were enrolled in 2010 and followed up for 4 years. New cases of T2D were identified via the annual medical examination. Cox regression analysis was used to assess the association between VAI and incidence of T2D. Receiver operating characteristic curve and area under the curves (AUC) were applied to compare the prediction ability of T2D between VAI and other fatness indices. Results: During the 4-year follow-up, 153 (8.42%) of 1,817 men and 88 (3.89%) of 2,261 women developed T2D. The multivariable-adjusted hazards ratios for developing T2D in the highest tertile of VAI scores were 2.854 (95% CI 1.815-4.487) in men and 3.551 (95% CI 1.586-7.955) in women. The AUC of VAI was not higher than that of other fatness indices. Conclusions: VAI could predict the risk of T2D among Chinese adults, especially in women. However, the prediction ability of T2D risk for VAI was not higher than that of the other fatness indices.

Background In absence of curative treatments for dementia with type 2 diabetes mellitus (T2DM), mild cognitive impairment (MCI) in T2DM, the preclinical transitional states of dementia with T2DM has attracted dramatic attention. Our study was to estimate the prevalence and distribution of MCI in T2DM subjects from China, and identify influencing factors of subjects in MCI with T2DM. Methods In the present study, we performed cluster random sampling of 8213 people aged 65 years and older in Tianjin, a metropolitan city, located in northern China. All participants were interviewed and screened for T2DM. 1109 subjects with T2DM were initially screened with American Diabetes Association criteria for diagnosis of diabetes mellitus and were diagnosed with MCI and dementia according to the criteria of DSM-IIIR. The prevalence of MCI and dementia in subjects with T2DM were compared with that in ordinary subjects. Logistic regression analyses were performed to evaluate risk of MCI with T2DM. Results Among all 8213 subjects, overall MCI and dementia with T2DM prevalence were 13.5% and 2.34%, respectively. Compared with ordinary subjects, the prevalence of MCI in the present study was more frequent than the prevalence of MCI for the general population in almost each age group. In the univariate analyses, among all diabetic subjects, compared with cognitive intactly subjects, MCI subjects had significantly higher levels of age, current smoking, mean waist circumference, duration from onset of diabetes, insulin intake, systolic BP, fasting plasma glucose (FPG), glycosylated hemoglobin (HbA1c) and immunoreactive insulin (IRI). In multivariate logistic regression analyses, variables including current smoking, duration from onset of diabetes, FPG, HbA1c and IRI were significantly associated with increased risk for MCI with T2DM, the ORs were 1.36,1.33,1.17,1.25 and 1.33, respectively (all P Conclusions The present study confirms the high prevalence of MCI with T2DM among the elderly population of China. T2DM is related to a higher risk of MCI in a population with a high prevalence of this disorder and may aggravate the clinical picture as a concomitant factor.

Dementia has emerged as a major societal issue because of the worldwide aging population and the absence of any effective treatment. DNA methylation is an epigenetic mechanism that evidently plays a role in Alzheimer's disease (AD). Folate acts through one-carbon metabolism to support the methylation of multiple substrates including DNA. We aimed to test the hypothesis that folic acid supplementation alters DNA methylation profiles in AD models. Mouse Neuro-2a cells expressing human APP695 (N2a-APP cells) were incubated with folic acid (2.8-20 μmol/L). AD transgenic mice were fed either folate-deficient or control diets and gavaged daily with water or folic acid (600 μg/kg). Gene methylation profiles were determined by methylated DNA immunoprecipitation-DNA microarray (MeDIP-chip). Differentially methylated regions (DMRs) were determined by Quantitative Differentially Methylated Regions analysis, and differentially methylated genes (DMGs) carrying at least three DMRs were selected for pathway analysis. Folic acid up-regulated DNA methylation levels in N2a-APP cells and AD transgenic mouse brains. Functional network analysis of folic acid-induced DMGs in these AD models revealed subnetworks composed of 24 focus genes in the janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling pathway and 12 focus genes in the long-term depression (LTD) signaling pathway. In conclusion, these results revealed a role for folic acid in the JAK-STAT and LTD signaling pathways which may be relevant to AD pathogenesis. This novel finding may stimulate reinvestigation of folic acid supplementation as a prophylactic or therapeutic treatment for AD.

Background: Inflammation plays a significant role in the pathophysiology of cognitive impairment in previous studies. Neutrophil-lymphocyte ratio (NLR) is a reliable measure of systemic inflammation. Objective: The aim of this study was to investigate the association between NLR and mild cognitive impairment (MCI), and further to explore the diagnostic potential of the inflammatory markers NLR for the diagnosis of MCI in elderly Chinese individuals. Methods: 186 MCI subjects and 153 subjects with normal cognitive function were evaluated consecutively in this study. Neutrophil (NEUT) count and Lymphocyte (LYM) count were measured in fasting blood samples. The NLR was calculated by dividing the absolute NEUT count by the absolute LYM count. Multivariable logistic regression was used to evaluate the potential association between NLR and MCI. NLR for predicting MCI was analyzed using Receiver Operating Characteristic (ROC) curve analysis. Results: The NLR of MCI group was significantly higher than that of subjects with normal cognitive function (2.39 ± 0.55 vs. 1.94 ± 0.51, P < 0.001). Logistic regression analysis showed that higher NLR was an independent risk factor for MCI (OR: 4.549, 95% CI: 2.623-7.889, P < 0.001). ROC analysis suggested that the optimum NLR cut-off point for MCI was 2.07 with 73.66% sensitivity, 69.28% specificity, 74.48% Positive Predictive Values (PPV) and 68.36% negative predictive values (NPV). Subjects with NLR ≥ 2.07 showed higher risk relative to NLR < 2.07 (OR: 5.933, 95% CI: 3.467-10.155, P < 0.001). Conclusion: The elevated NLR is significantly associated with increased risk of MCI. In particular, NLR level higher than the threshold of 2.07 was significantly associated with the probability of MCI.

Recent studies revealed that folic acid deficiency (FD) increased the likelihood of stroke and aggravated brain injury after focal cerebral ischaemia. The microglia‐mediated inflammatory response plays a crucial role in the complicated pathologies that lead to ischaemic brain injury. However, whether FD is involved in the activation of microglia and the neuroinflammation after experimental stroke and the underlying mechanism is still unclear. The aim of the present study was to assess whether FD modulates the Notch1/nuclear factor kappa B (NF‐κB) pathway and enhances microglial immune response in a rat middle cerebral artery occlusion‐reperfusion (MCAO) model and oxygen‐glucose deprivation (OGD)‐treated BV‐2 cells. Our results exhibited that FD worsened neuronal cell death and exaggerated microglia activation in the hippocampal CA1, CA3 and Dentate gyrus (DG) subregions after cerebral ischaemia/reperfusion. The hippocampal CA1 region was more sensitive to ischaemic injury and FD treatment. The protein expressions of proinflammatory cytokines such as tumour necrosis factor‐α, interleukin‐1β and interleukin‐6 were also augmented by FD treatment in microglial cells of the post‐ischaemic hippocampus and in vitro OGD‐stressed microglia model. Moreover, FD not only dramatically enhanced the protein expression levels of Notch1 and NF‐κB p65 but also promoted the phosphorylation of pIkBα and the nuclear translocation of NF‐κB p65. Blocking of Notch1 with N‐[N‐(3, 5‐difluorophenacetyl)‐l‐alanyl]‐S‐phenylglycine t‐butyl ester partly attenuated the nuclear translocation of NF‐κB p65 and the protein expression of neuroinflammatory cytokines in FD‐treated hypoxic BV‐2 microglia. These results suggested that Notch1/NF‐κB p65 pathway‐mediated microglial immune response may be a molecular mechanism underlying cerebral ischaemia‐reperfusion injury worsened by FD treatment.

Periconceptional maternal folate levels may alter DNA methylation patterns and health outcomes in offspring. We hypothesized that maternal folic acid supplementation alters fetal neural development through DNA methylation in the fetal brain. Twenty-eight rats were randomly assigned to four groups: three groups of the female rats were fed folate-normal, folate-deficient or folate-supplemented diets from seven days before mating to delivery. In another group, folic acid supplementation diet short-period group was fed a folate-normal diet, except for 10 days (begin mating) when this group was fed a folate-supplemented diet. After delivery, the diets were changed to folate-normal diet for all four groups. The cliff avoidance and forelimb grip tests were used to assess sensory motor function of rat offspring. The results indicate that maternal folic acid supplementation improved the early development of sensory-motor function in offspring. Maternal folic acid supplementation increased the methylation potential, global DNA methylation (5-mC) and DNA methyltransferase expression and activity in the brains of the offspring. In conclusion, maternal folic acid supplementation increases DNA methylation pattern in offspring brain and improves the early development of sensory-motor function.

To identify characteristics of neuropsychological function among elderly individuals with Type 2 diabetes mellitus with mild cognitive impairment (T2DM-MCI) and evaluate domain-specific effects of T2DM on cognition.This was a cross-sectional study conducted in Tianjin, China. MCI subjects (n=246) and controls were identified in elderly individuals with diabetes, and groups were matched in a 1:1 ratio for sex, age and educational level. Cognitive function was assessed using WAIS-III (block design, digit span), Trail Making Test A, Trail Making Test B, WMS-III (word list learning, logical memory), verbal fluency and MMSE. We used multivariable logistic regression to find diabetic factors associated with MCI.The mean MMSE score was 22.73 ± 2.32 in subjects with T2DM-MCI, versus 26.71 ± 2.43 in subjects cognitive normal (P0.001). Executive and visuospatial functions were more impaired in individuals with T2DM-MCI than in those without, as assessed using block design (P0.001), digit span test (P0.001), and Trails B (P0.001). For memory, subjects with T2DM-MCI did worse than those cognitive normal on the word learning list delayed recall (P=0.015). Diabetic-related factors such as longer duration of T2DM, higher HbA1c, insulin treatment was associated with a lower level of cognitive functioning using MMSE, block design, delayed recall and Trails B test.T2DM should be considered a risk factor for MCI. This risk may be associated with duration of diabetes, use of glucose-lowering medications, degree of glucose control. To decrease risk of MCI, it is important to monitor glucose control and adjust medications appropriately in elderly patients.

Alzheimer’s disease (AD) is a highly prevalent type of dementia. The epigenetic mechanism of gene methylation provides a putative link between nutrition, one-carbon metabolism, and disease progression because folate deficiency may cause hypomethylation of promoter regions in AD-relevant genes. We hypothesized that folic acid supplementation may protect neuron cells from amyloid β (Aβ) oligomer-induced toxicity by modulating DNA methylation of APP and PS1 in AD models. Primary hippocampal neuronal cells and hippocampal HT-22 cells were incubated for 24 h with a combination of folic acid and either Aβ oligomers or vehicle and were then incubated for 72 h with various concentrations of folic acid. AD transgenic mice were fed either folate-deficient or control diets and gavaged daily with various doses of folic acid (0 or 600 μg/kg). DNA methyltransferase (DNMT) activity, cell viability, methylation potential of cells, APP and PS1 expression, and the methylation of the respective promoters were determined. Aβ oligomers lowered DNMT activity, increased PS1 and APP expression, and decreased cell viability. Folic acid dose-dependently stimulated methylation potential and DNMT activity, altered PS1 and APP promoter methylation, decreased PS1 and APP expression, and partially preserved cell viability. Folic acid increased PS1 and APP promoter methylation in AD transgenic mice. These results suggest a mechanism by which folic acid may prevent Aβ oligomer-induced neuronal toxicity.

Previous studies have indicated that higher levels of food consumption are associated with fatty liver disease (FLD), but few studies have investigated the relationship between this disease and different dietary patterns. The aim of this cross-sectional study was to examine the association between dietary patterns and FLD in adults.Dietary intakes of participants in the Tianjin were assessed via questionnaire. Factor analysis was used to identify dietary patterns, and FLD was defined as having a FLD diagnosis using liver ultrasonography. Relationships between dietary patterns and FLD were assessed using multiple logistic regression analysis.Female participants in the highest quartile of high-carbohydrate/sweet pattern scores had a 2.19-fold greater risk (95% confidence interval (CI), 1.40-3.46) of developing non-alcoholic FLD (NAFLD) than those in the lowest quartile after adjusting for confounding factors. No significant differences were found between any dietary pattern and NAFLD in males. In males, a significantly increasing trend of alcoholic FLD (AFLD) prevalence was associated with increasing high-protein/cholesterol pattern scores (P for trend = 0.03; odds ratio (OR), 2.08; 95% CI, 1.15-3.81) while an increased high-carbohydrate/sweet pattern score appeared protective against AFLD (P for trend = 0.02; OR, 0.55; 95% CI, 0.29-1.00).Our study demonstrates that high-protein/cholesterol pattern scores are associated with higher prevalence of AFLD in males. We also show high-carbohydrate/sweet pattern scores are associated with higher prevalence of NAFLD in females; but, interestingly, this pattern shows a favorable effect on AFLD in males.

Background Elevated plasma homocysteine (Hcy) levels have been indicated as a strong and modifiable risk factor of ischemic stroke; the previous studies have shown that exposure to Hcy activates cultured microglia. However, whether neurotoxicity of Hcy involves microglia activation following brain ischemia and the underlying mechanisms remains incompletely understood. Methods The cerebral damage was evaluated by staining with 2,3,5-triphenyltetrazolium chloride, hematoxylin-eosin, and Fluoro Jade B. The activation state of microglia was assessed via immunoreaction using the microglial markers Iba1 and OX-42. Then, the inflammatory factors such as tumor necrosis factor α (TNF-α), interleukin 6 (IL-6), and phosphorylated signal transducer and activator of transcription 3 (pSTAT3) were examined by Western blot analysis and fluorescence immunohistochemistry. Results Elevated Hcy level augmented brain damage and neural cell toxicity in the brain cortex and the dentate gyrus region of the hippocampus after cerebral ischemia/reperfusion. Meanwhile, Hcy activated microglia and induced the expression of the inflammatory factors such as TNF-α and IL-6. Moreover, Hcy caused an increase in pSTAT3 expression which occurs in microglial cells. AG490, a JAK2-STAT3 inhibitor, effectively inhibited the phosphorylation of STAT3, microglial cell activation and the secretion of IL-6, TNF-α raised by Hcy treatment. Conclusions STAT3 signaling pathway located in microglia plays a critical role in mediating Hcy-induced activation of microglia and neuroinflammation in rat MCAO model. This suggests the feasibility of targeting the JAK2/STAT3 pathway as an effective therapeutic strategy to alleviate the progression of Hcy-associated ischemia stroke. Electronic supplementary material The online version of this article (10.1186/s12974-017-0963-x) contains supplementary material, which is available to authorized users.

Homocysteine (Hcy) is a risk factor for brain atrophy, cognitive impairment, and dementia. Vitamin B12 and folate are cofactors necessary for the methylation of Hcy. However, there is some debate regarding the differing levels of plasma Hcy and serum folate and vitamin B12 among healthy controls, patients with mild cognitive impairment (MCI), and patients with Alzheimer’s disease (AD). This study aimed to evaluate how the levels of plasma Hcy and its biological determinants, folate and vitamin B12, are related to MCI and AD in older Chinese adults. This is a case-control study including 112 subjects with MCI, 89 AD patients and 115 healthy controls. Diagnosis of AD was made according to the NINCDS-ADRDA and MCI with modified Petersen’s criteria. Serum folate and vitamin B12 concentrations were analyzed by radioimmunoassay, and plasma Hcy was assessed by a high-performance liquid chromatography-fluorescence method. Multivariate analysis of regression was used to examine the odds ratio (OR) of MCI or AD with Hcy or vitamin levels. Results have shown that serum folate and vitamin B12 levels were significantly lower, but the plasma Hcy level was higher, in patients with MCI and AD than in healthy controls. Multivariate regression analyses showed that subjects in the lowest folate tertile had significantly higher adjusted ORs for MCI (OR: 3.07; 95% confidence interval [CI]: 1.12, 8.07) and AD (3.42; 95% CI: 1.15, 8.34) compared to subjects in the highest tertile. The highest Hcy tertile was significantly associated with MCI (adjusted OR: 2.81; 95% CI: 1.15, 4.73) and AD (adjusted OR: 3.64; 95% CI: 1.13, 9.04) compared to the lowest tertile. No association existed between low vitamin B12 levels and AD or MCI (p > 0.05). Low blood levels of folate and vitamin B12 and elevated Hcy levels were associated with MCI and AD in older Chinese adults, and the association was stronger for AD.

The role of homocysteine (Hcy) in the pathogenesis of coronary artery disease (CAD) is controversial, as decreased Hcy levels have not demonstrated consistent clinical benefits. Recent studies propose that S-adenosylhomocysteine (SAH), and not Hcy, plays a role in cardiovascular disease (CVD). We aimed to assess the relationship between plasma SAH and coronary artery lesions. Participants (n=160; aged 40-80years) with chest pain and suspected CAD underwent coronary angiography (CAG) for assessment of coronary artery stenosis, and were assigned to either the atherosclerosis (AS) or CAD group. Plasma SAH and S-adenosylmethionine (SAM) concentrations were measured and the association between coronary artery lesions and SAH was assessed. SAH levels were significantly higher in the CAD group (23.09±2.4nmol/L) than in the AS group (19.2±1.5nmol/L). While the AS group had higher values for SAM/SAH (5.1±0.7 vs. 4.1±1.1), levels of SAM, Hcy, folate, and vitamin B12 were similar in the two groups. Coronary artery lesions were associated with SAH (β=11.8 [95% CI: 5.88, 17.7, P

Atherosclerosis is a chronic disease that can seriously endanger human life. Folic acid supplementation modulates several disorders, including atherosclerosis, via its antiapoptotic and antioxidative properties. This study investigated whether folic acid alleviates atherogenesis by restoring homocysteine levels and antioxidative capacity in atherosclerosis Wistar rats. To this end, 28 Wistar rats were randomly divided into 4 groups (7 rats/group) as follows: (i) wild-type group, fed only the AIN-93 semi-purified rodent diet (folic acid: 2.1 mg/kg); (ii) high-fat + folic acid-deficient group (HF+DEF) (folic acid: 0.2 mg/kg); (iii) high-fat + normal folic acid group (folic acid: 2.1 mg/kg); and (iv) high-fat + folic acid-supplemented group (folic acid: 4.2 mg/kg). After 12 weeks, histopathological changes in the atherosclerotic lesions of the aortic arch were determined. In addition, serum folate levels, plasma homocysteine levels, plasma S-adenosyl-homocysteine levels, antioxidant status, oxidant status, and lipid profiles were evaluated. The results show aggravated atherosclerotic lesions in the HF+DEF group. Folic acid supplementation increased concentrations of serum folate. Further, folic acid supplementation increased high-density lipoprotein-cholesterol, decreased plasma homocysteine levels, and improved antioxidant capacity in atherogenic rats. These findings are consistent with the hypothesis that folic acid alleviates atherogenesis by reducing plasma homocysteine levels and improving antioxidant capacity in rats fed a high-fat diet.

Homocysteine (Hcy) has been shown to have a neurotoxic effect on ischemic brain cells; however, the underlying mechanisms remain incompletely understood. Here, we examined whether Hcy treatment influences mitochondria injury, oxidative stress, and mitochondrial STAT3 (mitoStat3) expression in rat ischemic brain. Our results demonstrated that Hcy treatment aggravated the damage of mitochondrial ultrastructure in the brain cortex and the dentate gyrus region of the hippocampus after focal cerebral ischemia. An elevated Hcy level was also accompanied by the significant inhibition of mitochondrial complex I–III enzymatic activities in addition to an increase in cytochrome c release. 8-Hydroxy-2′-deoxyguanosine (8-OHdG) content and mitoStat3 protein phosphorylation level were increased in Hcy-treated animals, whereas AG490, a Jak2 inhibitor, inhibited mitoStat3 phosphorylation as well as 8-OHdG levels induced by Hcy. In vitro studies revealed that Hcy also markedly increased reactive oxygen species (ROS) and mitoStat3 levels. In addition, the inhibition of pSTAT3 reduced Hcy-mediated increase in ROS levels, whereas quenching ROS using the ROS inhibitor glutathione ethyl ester inhibited Hcy-mediated pSTAT3 overactivation in Neuro2a cells. These findings suggest that the development of therapies that interfere with the ROS/pSTAT3 pathway may be helpful for treating cerebral infarction-related diseases associated with Hcy.

Sarcopenia is characterized by the age-related loss of muscle mass and strength, which results in higher mortality in aged people. One of the mechanisms of the sarcopenia is the loss in the function and number of muscle satellite cells. Chronic low-grade inflammation plays a central role in the pathogenesis of age-related sarcopenia. Accumulating evidence suggests that coffee, one of the most widely consumed beverages in the world, has potential pharmacological benefits such as anti-inflammatory and anti-oxidant effects. Since these effects may improve sarcopenia and the functions of satellite cells, we examined the effects of coffee on the skeletal muscles in an animal model using aged mice. In vivo, coffee treatment attenuated the decrease in the muscle weight and grip strength, increased the regenerating capacity of injured muscles, and decreased the serum pro-inflammatory mediator levels compared to controls. In vitro, using satellite cells isolated from aged mice, coffee treatment increased the cell proliferation rate, augmented the cell cycle, and increased the activation level of Akt intra-cellular signaling pathway compared to controls. These findings suggest that the coffee treatment had a beneficial effect on age-related sarcopenia.

This study aimed to evaluate whether folic acid supplementation would improve cognitive performance by reducing serum inflammatory cytokine concentrations. This RCT was performed in Tianjin, China. Participants with mild cognitive impairment (MCI) were randomly assigned to the folic acid (400 μg/day) or conventional treatment groups. Neuropsychological tests were administered, and folate, homocysteine, vitamin B12, IL-6, TNF-α, Aβ-42, and Aβ-40 were measured at baseline and at 6- and 12-month time points.152 participants (folic acid: 77, conventional: 75) completed the trial. Significant improvements in folate (ηp2 = 0.703, P = 0.011), homocysteine (ηp2 = 0.644, P = 0.009), Aβ-42 (ηp2 = 0.687, P = 0.013), peripheral IL-6 (ηp2 = 0.477, P = 0.025), TNF-α (ηp2 = 0.709, P = 0.009) levels were observed in folic acid group compared with conventional group. Folic acid supplementation improved the Full Scale Intelligence Quotient (P = 0.028; effect size d = 0.153), Information (P = 0.031; d = 0.157) and Digit Span (P = 0.009; d = 0.172) scores at 12 months compared with conventional treatment. Based on these findings, daily oral administration of a 400-μg folic acid supplement to MCI subjects for 12 months can significantly improve cognitive performance and reduce peripheral inflammatory cytokine levels.

Background Lack of physical activity is a growing problem in China, due to the fast economic development and changing living environment over the past two decades. The aim of this review is to summarize the factors related to physical activity in Chinese children and adolescents during this distinct period of development. Methods A systematic search was finished on Jan 10th, 2017, and identified 2200 hits through PubMed and Web of Science. English-language published studies were included if they reported statistical associations between factors and physical activity. Adapted criteria from the Strengthening The Reporting of OBservational studies in Epidemiology (STROBE) statement and evaluation of the quality of prognosis studies in systematic reviews (QUIPS) were used to assess the risk of bias of the included studies. Related factors that were reported in at least three studies were summarized separately for children and adolescents using a semi-quantitative method. Results Forty two papers (published 2002–2016) were included. Most designs were cross-sectional (79%), and most studies used questionnaires to assess physical activity. Sample size was above 1000 in 18 papers (43%). Thirty seven studies (88%) showed acceptable quality by methodological quality assessment. Most studies reported a low level of physical activity. Boys were consistently more active than girls, the parental physical activity was positively associated with children and adolescents’ physical activity, children in suburban/rural regions showed less activity than in urban regions, and, specifically in adolescents, self-efficacy was positively associated with physical activity. Family socioeconomic status and parental education were not associated with physical activity in children and adolescents. Conclusions The studies included in this review were large but mostly of low quality in terms of study design (cross-sectional) and methods (questionnaires). Parental physical activity and self-efficacy are promising targets for future physical activity promotion programmes. The low level of physical activity raises concern, especially in suburban/rural regions. Future research is required to enhance our understanding of other influences, such as the physical environment, especially in early childhood. Electronic supplementary material The online version of this article (doi:10.1186/s12966-017-0486-y) contains supplementary material, which is available to authorized users.

Although we have found that protease-treated royal jelly (pRJ) benefit for the skeletal muscle mass and strength in the aged animals, the potential beneficial effects have not been evaluated in humans. The aim of this study was to determine whether pRJ intake had beneficial effects on muscle strength in elderly nursing home residents. One hundred and ninety-four subjects enrolled into this multicenter, randomized, double-blind, placebo-controlled study. Subjects received either placebo(Group 1), pRJ 1.2 g/d(Group 2), or 4.8 g/d(Group 3). Data through 1 year are reported for 163 subjects. The primary outcome measure is handgrip strength. Secondary outcomes include several physical performance tests (six-minute walk test, timed up and go test, and standing on one leg with eyes closed). The dropout rate was 16.0%. The means (95% confidence interval) of change in handgrip strength for placebo, low-dose, and high-dose groups are −0.98(−2.04,0.08), 0.50(−0.65,1.65) and 1.03(−0.37,2.44) kg (P = 0.06, P for trend = 0.02), respectively. No significant effects of the interventions were observed for physical performances. These findings suggest that pRJ treatment might not improve, but rather attenuate the progression of decrease in muscle strength in elderly people. In addition, we have not found that pRJ intervention can achieve improvement or attenuating the decrease in physical performance.

Previous studies indicated that dietary patterns were associated with metabolic syndrome (MS), but little is known in Chinese. We design this case-control study to evaluate the associations between dietary patterns and MS in Chinese adults. In this study, 1492 participants with MS were matched with 1492 controls using the 1:1 ratio propensity score matching methods. Dietary intake was assessed using a valid self-administered food frequency questionnaire, and MS was defined in accordance with the criteria of the American Heart Association scientific statement of 2009. Higher scores for the high-protein/cholesterol pattern were associated with higher prevalence of MS. Compared with the participants in the lowest quartile, the odds ratio (OR) for the extreme quartile was 1.36 (95% confidence interval (CI), 1.10–1.68) and the P for trend

Background High lipid levels may constitute a more important risk factor for cognitive health in previous studies. However, the association of plasma lipids with mild cognitive impairment (MCI) among elderly people had not been studied exactly. This study aims to explore the relationship between plasma lipids/lipoproteins and the risk of MCI in elderly Chinese individuals. Methods CSI-MCI study was a preliminary case-control study of the association of plasma lipids/lipoproteins with MCI in 112 MCI cases and 115 cognitively normal controls. Plasma total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG) levels were measured in fasting blood samples. Multivariable logistic regression was used to evaluate the potential association between MCI and these factors. Statistical models were adjusted for multiple demographic and biological covariates. Results The subjects with MCI were significantly older, higher percentage of females and less educated than controls (P

Older adults can experience glucose metabolism dysfunction, and although manganese may help regulate glucose metabolism, there is little information regarding this association among older people. This cross-sectional study included 2402 Chinese adults who were ≥60 years old in 2013 (Tianjin, China), and evaluated the associations of serum manganese with prediabetes and diabetes. Serum manganese levels were measured using inductively coupled plasma mass spectrometry. Multivariable logistic regression models were used to evaluate the sex-specific associations of manganese levels with diabetes and prediabetes after adjusting for confounding factors (age, sex, life style factors, and health status). Based on the WHO criteria, prediabetes was observed in 15.1% of men and 13.4% of women, while diabetes was observed in 30.0% of men and 34.4% of women. In the final model, the odds ratios (95% confidence interval) for prediabetes according to manganese quartile were 1.000, 0.463 (0.269–0.798), 0.639 (0.383–1.065), and 0.614 (0.365–1.031) among men and 1.000, 0.773 (0.498–1.200), 0.602 (0.382–0.947), and 0.603 (0.381–0.953) among women (p for trend = 0.134 and 0.015, respectively). The lowest prevalence of diabetes among men occurred at a moderate range of serum manganese (p < 0.05). Therefore, appropriate serum manganese levels may help prevent and control prediabetes and diabetes.

The association of vitamin D status and inflammation prediabetes mellitus (PreDM) individuals has not been investigated. We investigated the association of serum 25-hydroxyvitamin DIn this cross-sectional study, we stratified 418 nondiabetic subjects as having PreDM or normal fasting glucose (NFG), and divided PreDM or NFG subjects into vitamin D sufficient, vitamin D insufficient and vitamin D deficient subgroups. 25(OH) DIn the PreDM group, compared with those in the vitamin D sufficient subgroup, vitamin D insufficient subgroup and vitamin D deficient subgroup had higher concentrations of hs-CRP and leptin (P0.05). In the PreDM-deficient or PreDM-insufficient subgroup, mean hs-CRP and leptin concentration was higher than in the PreDM-sufficient, NFG-deficient, NFG-insufficient and NFG-sufficient subgroups (P0.05). Serum 25(OH) D25(OH) D

Background/Aims: The prevalence of mild cognitive impairment (MCI) and its subtypes among Chinese older adults, and the contribution of vascular risk factors (VRF) and vascular disorders to MCI remain unclear. This study aims to investigate the prevalence of MCI and its different subtypes, and clarify the role of VRF and vascular diseases in the occurrence of MCI. Methods: A random sample of 5,214 nondementia (DSM-IV) individuals aged ≥65 years underwent neuropsychological assessments and clinical examinations. MCI, including amnestic MCI-single domain (aMCI-SD), amnestic MCI-multiple domains (aMCI-MD), nonamnestic MCI-single domain (naMCI-SD), and nonamnestic MCI-multiple domains (naMCI-MD), was defined according to modifications of the Petersen criteria. VRF (smoking, obesity, and diabetes) and vascular disorders (myocardial infarction, atrial fibrillation, stroke, and hypertension) were assessed based on information through self-report and medical records. Data were analyzed using multivariate logistic regression. Results: The prevalence of MCI was 11.33% (95% CI: 8.21-14.43), and that of aMCI-SD, aMCI-MD, naMCI-SD, and naMCI-MD was 4.48% (95% CI: 2.24-6.74), 2.09% (95% CI: 0.80-3.38), 4.22% (95% CI: 1.38-7.08), and 0.53% (95% CI: 0.32-0.75), respectively. The prevalence of MCI is higher in women than in men. Multivariate logistic regression analysis shows that VRF and vascular diseases were significantly related to increase the odds of MCI and its specific subtype. Conclusions: The prevalence of MCI is almost 11% among Chinese older adults. VRF and vascular disorders are associated with MCI, especially naMCI.

Folic acid (FA) deficiency is not only associated with an increased risk of ischemic stroke, but also with increased oxidative DNA damage and brain injury after cerebral ischemia-reperfusion. However, the cellular and molecular mechanisms underlying FA deficiency-associated neuropathogenesis are not completely understood. In the present study, we tested the hypothesis that neuronal autophagy in focal cerebral ischemia rats may be involved in the mechanisms of FA deficiency-induced injury to neuronal cells. The results demonstrated that, accompanied by obvious neuron damage, the expression of the autophagic markers LC3 and Beclin-1, and the formation of 8-OHdG (a marker of oxidative stress to DNA) and autophagosomes were significantly increased in the brain cortex after ischemia-reperfusion. FA deficiency further induced neuronal cell death, and significantly increased the formation of autophagosomes and the expression of LC3 and Beclin-1 in NeuN-positive cell bodies after ischemia-reperfusion. The elevated level of 8-OHdG was also observed in the ischemic cortex of FA deficiency-treated animals. Conversely, the neuronal cell injury, autophagosome accumulation and the effects of LC3 and Beclin1 overexpression caused by FA deficiency were partially blocked by an autophagic inhibitor 3-methyladenine. These results suggest that FA deficiency progresses autophagic activation and aggravates the damage in rat brain cortex following focal cerebral ischemia-reperfusion. The oxidative injury may be involved in cell morphological damage and autophagy alteration caused by FA deficiency.

The aim of this study was to compare the effect of high fruit and soybean products diet and standard diet interventions on serum uric acid (SUA) in asymptomatic hyperuricemia adults. A total of 187 Chinese adults (20-59 years old) with asymptomatic hyperuricemia participated in this randomized trial and were assigned to receive the standard diet recommended by guideline (group 1) and high fruit and soybean products diet (group 2) for 3 months. The outcome of SUA was assessed before and at the end of the intervention period. After 3 months, the SUA in group 1 and group 2 was significant reduced, whereas the SUA was not significantly changed in-between groups. These data suggest that over a 3-month period, although the high fruit and soybean products diet and standard diet interventions yield no different effects on SUA, the high fruit and soybean products dietary intervention could be an effective alternative to a standard diet for achieving clinically important reductions in SUA for asymptomatic hyperuricemia patients.

Background and Aims There is a growing focus on frontotemporal dementia (FTD). However, compared with other major dementias, very little is known about the factors associated with FTD. The present study evaluated candidate factors associated with FTD in the Chinese population. Methods One hundred eight elderly patients (36 diagnosed with FTD and 72 controls) of the Neurology Central Hospital of Tianjin (China), were diagnosed by neurologists, and recruited for the study between November 2011 and November 2014. Clinical evaluation, laboratory tests, brain images (computed tomography scans and magnetic resonance images), neuropsychological, and neuropsychiatric assessments were performed. The association between FTD and the variables was assessed using multiple binary logistic regression analyses adjusted for age and gender. Results With controls as the reference category, education was associated with the diagnosis of FTD (adjusted odds ratio [OR], 1.60; 95% confidence interval [CI]: 1.17–2.19). Serum vitamin B12 levels were associated with the diagnosis of FTD (adjusted OR, 0.99; 95% CI: 0.98–0.99). Serum low-density lipoprotein (LDL) levels were associated with the diagnosis of FTD (adjusted OR, 8.54; 95% CI: 2.86–25.49). Conclusions Education and serum LDL levels were positively associated with the diagnosis of FTD. Serum vitamin B12 levels were negatively associated with the diagnosis of FTD.