Association of folate intake with cardiovascular-disease mortality and all-cause mortality among people at high risk of cardiovascular-disease.

BACKGROUND & AIMS: Due to the beneficial effect of folate on cardiovascular disease (CVD), folic acid supplementation is a more common practice among people at high-risk of CVD. However, long-term prospective investigations regarding the association of folate-intake with CVD-mortality and all-cause mortality among this specific population are still lacking. Therefore, this study aims to assess the association of folate-intake with CVD-mortality and all-cause mortality. METHODS: A total of 14,234 participants at high-risk of CVD were enrolled. Total folate equivalent (TFE), dietary folate equivalent (DFE), food folate, folic acid in fortified food, folic acid supplements, serum folate and red blood cell (RBC) folate were measured. The main outcome measures were CVD-mortality and all-cause mortality from baseline until 31 December 2015. RESULTS: During the 98,890 person-year follow-up, 2036 deaths including 682 deaths due to CVD were documented. After multivariate adjustment, a J shaped association was found: modest intake of TFE and DFE was associated with lower risk of CVD-mortality and all-cause mortality, whereas higher intake did not persistently reduce these risks. Compared to the participants without folic acid supplementation matched 28-covariates using propensity score, folic acid supplementation was associated with higher risk of CVD-mortality (HR:1.44, 95%CI:1.06-1.97, P = 0.022) and all-cause mortality (HR:1.28,95%CI:1.09-1.51, P = 0.003). The levels of serum-folate and RBC-folate in participants with folic acid supplementation were significantly greater than participants without folic acid supplementation (41.8 nmol/l vs. 64.2 nmol/l, P < 0.001 for serum-folate; 1201 nmol/l vs. 1608 nmol/l, P < 0.001 for RBC-folate). Compared with the lowest-quintile of serum-folate, the second-quintile was consistently associated with CVD-mortality (HR:0.72, 95%CI:0.53-0.99, P = 0.048) and all-cause mortality (HR:0.78, 95%CI:0.64-0.94, P = 0.013). Compared to the lowest-quintile of RBC-folate, the second-quintile was associated with lower all-cause mortality (HR:0.71,95%CI:0.56-0.90, P = 0.005), whereas the highest-quintile was associated with higher CVD-mortality (HR:1.40,95%CI:1.02-1.93, P = 0.030). The J shaped association of serum-folate and RBC-folate with CVD-mortality and all-cause mortality was also demonstrated, further supporting the results of TFE and propensity score analysis. CONCLUSIONS: This study suggested the beneficial effects of modest folate-intake on the improvement of long-term survival, and emphasized the potentially deleterious effects of excess folic acid supplementation among US adults at high-risk of CVD.

The future of prevention and treatment of diabetes with nutrition in China.

The significant transformation of dietary patterns in China has contributed to an increasing prevalence of type 2 diabetes over the past few decades. In this article, we comprehensively summarize the epidemiological characteristics of diabetes in China and further discuss major nutritional risk factors for diabetes. Although China has committed to combat diabetes through health system reform and national initiatives, the burden of diabetes remains a major challenge, with an increased premature mortality for the population. We therefore provide several recommendations for the nation's future diabetes agenda, with the aim of establishing an environment of healthy nutrition through multi-sectoral government and community engagement, and novel, robust scientific research.

The association of minerals intake in three meals with cancer and all-cause mortality: the U.S. National Health and Nutrition Examination Survey, 2003-2014.

BACKGROUND: Intake time of diet has recently been demonstrated to be associated with the internal clock and circadian pattern. However, whether and how the intake time of minerals would influence the natural course of cancer was largely unknown. METHODS: This study aimed to assess the association of mineral intake at different periods with cancer and all-cause mortality. A total of 27,455 participants aged 18-85 years old in the National Health and Nutrition Examination Survey were recruited. The main exposures were the mineral intakes in the morning, afternoon and evening, which were categorized into quintiles, respectively. The main outcomes were mortality of cancer and all causes. RESULTS: During the 178,182 person-years of follow-up, 2680 deaths, including 601 deaths due to cancer, were documented. After adjusting for potential confounders, compared to the participants who were in the lowest quintile(quintile-1) of mineral intakes at dinner, the participants in the highest quintile intake(quintile-5) of dietary potassium, calcium and magnesium had lower mortality risks of cancer (HRpotassium = 0.72, 95% CI:0.55-0.94, P for trend = 0.023; HRcalcium = 0.74, 95% CI:0.57-0.98, P for trend = 0.05; HRmagnesium = 0.75, 95% CI:0.56-0.99, P for trend = 0.037) and all-cause (HRpotassium = 0.83, 95% CI:0.73-0.94, P for trend = 0.012; HRcalcium = 0.87, 95% CI:0.76-0.99, P for trend = 0.025; HRmagnesium = 0.85, 95% CI:0.74-0.97, P for trend = 0.011; HRcopper = 0.80, 95%CI: 0.68-0.94, P for trend = 0.012). Further, equivalently replacing 10% of dietary potassium, calcium and magnesium consumed in the morning with those in the evening were associated with lower mortality risk of cancer (HRpotassium = 0.94, 95%CI:0.91-0.97; HRcalcium = 0.95, 95%CI:0.92-0.98; HRmagnesium = 0.95, 95%CI: 0.92-0.98). CONCLUSIONS: This study demonstrated that the optimal intake time of potassium, calcium and magnesium for reducing the risk of cancer and all-cause mortality was in the evening.

The joint effect of energy reduction with calcium supplementation on the risk factors of type 2 diabetes in the overweight population: a two-year randomized controlled trial.

Both excessive energy intake and low calcium intake are inversely associated with the aging-related diseases, particularly for type 2 diabetes mellitus(T2DM). This study examined whether energy reduction coupled with calcium supplementation aided in the prevention of T2DM among the overweight population. A randomized controlled trial(RCT) of 1021 overweight participants was performed, in which participants were randomly assigned to 4 groups: 1) energy-reduction group(ERG), 2) calcium supplementation group(CSG), 3) energy-reduction with calcium supplementation group(ER-CSG), 4) control group(CG). Nutritional habits, anthropometric and diabetes-related indicators were measured at baseline and each follow-up time. To analyze the separate effects of dietary energy reduction and calcium supplementation, ERG and ER-CSG were integrated into ERGs. Similarly, CSG and ER-CSG were integrated into CSGs. Compared to the non-energy-reduction groups(NERGs), ERGs had lower values of ΔBMI(-0.9kg/m2), ΔFSG (-0.34mmol/L), ΔHbA1c(0.16%), and ΔHOMA-IR(-0.13), and higher value of ΔGutt index(-5.82). Compared to the non-calcium supplementation groups(NCSGs), the ΔGutt index(-5.46) in CSGs showed a significant decrease. Moreover, these risk factors for T2DM were most effectively ameliorated in ER-CSG group with the decreased values of ΔFSG(-0.42mmol/L), ΔGutt index(-0.73), and the slowest increasing rate value of Δ2h-glucose(0.37mmol/L). This RCT demonstrated that energy-reduction with calcium supplementation was a useful dietary intervention strategy for preventing the development of T2DM in the overweight population.

Screening and development of monoclonal antibodies for identification of ferret T follicular helper cells.

The ferret is a key animal model for investigating the pathogenicity and transmissibility of important human viruses, and for the pre-clinical assessment of vaccines. However, relatively little is known about the ferret immune system, due in part to a paucity of ferret-reactive reagents. In particular, T follicular helper (Tfh) cells are critical in the generation of effective humoral responses in humans, mice and other animal models but to date it has not been possible to identify Tfh in ferrets. Here, we describe the screening and development of ferret-reactive BCL6, CXCR5 and PD-1 monoclonal antibodies. We found two commercial anti-BCL6 antibodies (clone K112-91 and clone IG191E/A8) had cross-reactivity with lymph node cells from influenza-infected ferrets. We next developed two murine monoclonal antibodies against ferret CXCR5 (clone feX5-C05) and PD-1 (clone fePD-CL1) using a single B cell PCR-based method. We were able to clearly identify Tfh cells in lymph nodes from influenza infected ferrets using these antibodies. The development of ferret Tfh marker antibodies and the identification of ferret Tfh cells will assist the evaluation of vaccine-induced Tfh responses in the ferret model and the design of novel vaccines against the infection of influenza and other viruses, including SARS-CoV2.

Clinical efficacy of laser combined with menstrual regulation in the treatment of female melasma: a retrospective study.

The aim of this study was to evaluate the clinical efficacy of using a Medlite C6 Q-switch Nd:YAG laser combined with menstrual regulation-based traditional Chinese medicine (TCM) in the treatment of female melasma. Forty cases of female patients with melasma, who were treated between December 2013 and December 2015 at the Jiangsu Provincial Hospital of Traditional Chinese Medicine, were reviewed retrospectively. Twenty patients received Q-switch Nd:YAG 1064 nm laser treatments combined with menstrual regulation treatments (experimental group), and 20 patients were treated only with the laser (control group). All treatments lasted for 6 months. The patients' faces were photographed before, immediately, and 6 months after treatment. The therapeutic efficacy was assessed by the reduction in the Melasma Area and Severity Index (MASI) score and the total skin damage score, and this was then compared between the two groups. Immediately and 6 months after the treatment, both the MASI and total skin damage scores in the experimental group were significantly lower compared to those in the control group (P < 0.001). The experimental group had significantly higher basic recovery and effectiveness rates than the control group (P = 0.020 and P = 0.008, respectively) and had a significantly lower invalidity rate (P < 0.001). Results from Medlite C6 Q-switch Nd:YAG laser treatment combined with menstrual regulation are superior than those obtained using only a laser for the treatment of female melasma.

Effects of pyrolysis temperature and addition proportions of corncob on the distribution of products and potential energy recovery during the preparation of sludge activated carbon.

The potential energy recovery during sludge activated carbon (SAC) preparation by co-pyrolysis of sewage sludge and biomass has recently gained significant attention. This study firstly evaluated the distribution of pyrolysis products including SAC, oils and gases during sludge pyrolysis at different temperatures (400 °C-800 °C) and corncob addition proportions (0-50%, w/w). The results demonstrated that with the increase of pyrolysis temperature, yield of SAC declined dramatically, while yields of pyrolysis oils and gases increased. With increasing addition of corncob, the yields of SAC and pyrolysis oils declined slightly, while the yield of gases generally increased. Then, the potential energy recovery during sludge pyrolysis was calculated, and the highest energy recovery value was 10.21 kJ/g achieved at 800 °C and 50% corncob addition. However, higher pyrolysis temperature over 600 °C resulted in lower yield and iodine adsorption capacity of SAC. Therefore, the suitable conditions were suggested to be at 600 °C with 50% corncob addition considering both adsorption performance of SAC and potential energy recovery efficiency.

Efficacy and Safety of Acupuncture for Essential Hypertension: A Meta-Analysis.

BACKGROUND The aim of this study was to assess the efficacy and safety of acupuncture therapy for patients with hypertension. MATERIAL AND METHODS We searched PubMed, Embase, the Cochrane Library, the Chinese Biomedical Literature Database, the Chinese National Knowledge Infrastructure, and the Wan-fang Data Database from inception through 29 April 2017. Randomized controlled trials investigating acupuncture therapy for hypertension were included. Review Manager 5.3 software was used for the data analysis. RESULTS A total of 30 RCTs involving 2107 patients were included. The overall methodological quality of the included studies was low. Pooled results demonstrate that acupuncture plus anti-hypertensive drugs is better than anti-hypertensive drugs alone at reducing systolic and diastolic blood pressure (SBP and DBP). The same result was observed for pooled data from experiments that compared acupuncture plus medication to sham acupuncture plus medication at reducing SBP and DBP. However, studies reveal that using acupuncture alone or anti-hypertensive drugs alone do not differ in the effect on lowering blood pressure. Similarly, acupuncture alone also did not differ from sham acupuncture alone, and electroacupuncture versus anti-hypertensive drugs was not significantly different at reducing SBP and DBP. CONCLUSIONS Our systematic review indicates there is inadequate high quality evidence that acupuncture therapy is useful in treating hypertension, as the exact effect and safety of acupuncture therapy for hypertension is still unclear. Therefore, research with larger sample sizes and higher-quality RCTs is still needed.

Genistein-Specific G6DT Gene for the Inducible Production of Wighteone in Lotus japonicus.

Prenylated isoflavonoids have been found in several legume plants, and they possess various biological activities that play important roles in both plant defense and human health. However, it is still unknown whether prenylated isoflavonoids are present in the model legume plant Lotus japonicus. In the present study, we found that the prenylated isoflavonoid wighteone was produced in L. japonicus when leaf was supplemented with genistein. Furthermore, a novel prenyltransferase gene, LjG6DT, was identified, which shared high similarity with and was closely related to several known prenyltransferase genes involved in isoflavonoid biosynthesis. The recombinant LjG6DT protein expressed in yeast exhibited prenylation activity toward genistein as an exclusive substrate, which produced wighteone, a prenylated genistein at the C-6 position that occurs normally in legume plants. The LjG6DT-green fluorescent protein (GFP) fusion protein is targeted to plastids. The transcript level of LjG6DT is induced by glutathione, methyl jasmonate and salicylic acid, implying that LjG6DT is involved in stress response. Overexpression of LjG6DT in L. japonicus hairy roots led to increased accumulation of wighteone when genistein was supplied, indicating that LjG6DT is functional in vivo. Feeding assays with the upstream intermediate naringenin revealed that accumulation of wighteone in L. japonicus was dependent on genistein supplementation, and accumulation of wighteone is competed by genistein methylation. This study demonstrated that phytoalexin wighteone is inducibly produced in L. japonicus, and it provides new insight into the biosynthesis and accumulation of prenylated isoflavonoids in legume plants.

The toxic influence of dibromoacetic acid on the hippocampus and pre-frontal cortex of rat: involvement of neuroinflammation response and oxidative stress.

Dibromoacetic acid (DBA) exsits in drinking water as a by-product of disinfection as a result of chlorination or ozonation processes. Hippocampus and pre-frontal cortex are the key structures in memory formation and weanling babies are more sensitive to environmental toxicant than adults, so this study was conducted to evaluate the potential neurotoxicity effects of DBA exposure when administered intragastrically for 4 weeks to weanling Sprague-Dawley rats, at concentration of 0, 20, 50, 125 mg/kg via the neurobehavioral and neurochemical effects. Results indicated that animals weight gain and food consumption were not significantly affected by DBA. However, morris water maze test showed varying degrees of changes between control and high-dose group. Additionally, the level of malondialdehyde (MDA) and generation of reactive oxygen species (ROS) in the hippocampus and pre-frontal cortex of rats increased significantly. The activities of total superoxide dismutase (SOD) and the glutathione (GSH) content in the hippocampus and pre-frontal cortex of rats decreased significantly after treatment with DBA. Treatment with DBA increased the protein and mRNA expression of Iba-1, NF-κB, TNF-α, IL-6, IL-1ß and HO-1 in the hippocampus and pre-frontal cortex of rats. These data suggested that DBA had a toxic influence on the hippocampus and pre-frontal cortex of rats, and that the mechanism of toxicity might be associated with the neuroinflammation response and oxidative stress.

DBA-induced caspase-3-dependent apoptosis occurs through mitochondrial translocation of cyt-c in the rat hippocampus.

Dibromoacetic acid (DBA), a by-product of disinfection, develops in drinking water during chlorination or ozonation processes. Water intake is the main source of DBA exposure in humans, which is potentially neurotoxic. The present study investigated the neurotoxic effects of DBA by assessing the behavioral and biochemical characteristics of Sprague Dawley rats intragastrically treated with DBA at concentrations of 20, 50 and 125 mg kg-1 body weight for 28 consecutive days. The results indicated that animal weight gain and food consumption were not significantly affected by DBA. However, shuttle box tests showed increases in mistake frequency and reaction latency between the control and high-dose group. We found significant changes in hippocampal neurons by histomorphological observation. Additionally, biochemical analysis indicated enhanced production of reactive oxygen species (ROS) resulting in disruption of cellular antioxidant defense systems including decreased mitochondrial superoxide dismutase (SOD) activity and release of cytochrome c (cyt-c) from mitochondria into the cytosol, which can induce neuronal apoptosis. Furthermore, the increase of cyt-c in the cytosol enhanced caspase-3 and caspase-9 activity, which was confirmed by poly ADP-ribose polymerase-1 (PARP-1) cleavage to its signature fragment of 85 kDa and decreased levels of protein kinase C-δ (PKC-δ) in the hippocampus. Meanwhile, DBA treatment caused differential modulation of apoptosis-associated proteins and mRNAs for phosphorylated apoptosis signal regulating kinase 1 (p-ASK-1), phosphorylated c-jun N-terminal kinase (p-JNK), cyt-c, Bax, Bcl-2, caspase-9 and cleaved caspase-3 accompanied by DNA damage. Taken together, these data indicate that DBA may induce neurotoxicity via caspase-3-dependent apoptosis involving mitochondrial translocation of cyt-c in the rat hippocampus.

[Acupuncture combined with medication for blood-stasis in unstable angina patients with different thrombolysis in myocardial infarction risk stratification].

OBJECTIVE: To observe the intervention effects of acupuncture combined with standardized treatment of western medicine on blood-stasis syndrome in unstable angina (UA) patients with different thrombolysis in myo-cardial infarction (TIMI) risk stratification. METHODS: According to TIMI risk score, a total of 72 UA patients were included, 24 cases in low-risk (0 to 2 points) group, 24 cases in moderate-risk (3 to 4 points) group and 24 cases in high-risk (5 to 7 points) group. Based on routine standardized treatment of western medicine, acupuncture was applied at Xinshu (BL 15), Xuehai (SP 10), Geshu (BL 17), Danzhong (CV 17), Jueyinshu (BL 14), Ximen (PC 4) and Neiguan (PC 6) in three groups. Acupuncture was given once a day, 14 days as a session. After one session, each symptom score and total score of blood stasis syndrome were observed. RESULTS: One patient dropped out respectively, and 23 patients in each group were included in the analysis. After treatment, the score of angina symptom and total score of blood stasis syndrome were significantly improved in three groups (all P<0.01). The improvements of each score and total score of blood stasis syndrome in the high-risk group were superior to those in the low-risk group and moderate-risk group (P<0.05, P<0.01). CONCLUSIONS: With the higher TIMI scores, the blood stasis syndrome is aggravated accordingly. Acupuncture combined with standardized treatment of western medicine could effectively intervene blood stasis syndrome, especially for the score of blood stasis syndrome of patients in high-risk group.

Male gametophyte-specific WRKY34 transcription factor mediates cold sensitivity of mature pollen in Arabidopsis.

Mature pollen is very sensitive to cold stress in chilling-sensitive plants. Plant WRKY DNA-binding transcription factors are key regulators in plant responses to abiotic and biotic stresses. Previous studies have suggested that WRKY34 (At4g26440) gene might be involved in pollen viability, although the mechanism involved is unclear. In this study, it is shown that cold treatment increased WRKY34 expression in the wild type, and promoter-GUS analysis revealed that WRKY34 expression is pollen-specific. Enhanced green fluorescent protein-tagged WRKY34 was localized in the nuclei. Pollen harbouring the wrky34 allele showed higher viability than pollen with the WRKY34 allele after cold treatment. Further functional analysis indicated that the WRKY34 transcription factor was involved in pollen development regulated by the pollen-specific MIKC* class of MADS-domain transcription factors under cold stress, and cold-insensitivity of mature wrky34 pollen might be partly attributable to the enhanced expression of transcriptional activator CBFs in the mutants. Thus, the WRKY34 transcription factor negatively mediated cold sensitivity of mature Arabidopsis pollen and might be involved in the CBF signal cascade in mature pollen.