Mechanism of omege-6 PUFA increasing the susceptibility to acute myocardial ischemia injury / 药学学报

The abnormal lipids metabolism is a critical pathological feature of coronary heart disease (CHD). Additional supplemental intake of polyunsaturated fatty acid (PUFA) has long been considered to be an effective strategy for preventing CHD, but more and more clinical trials have denied this view. Still, it is ambiguity for the specific mechanism of PUFA in CHD. The experimental programs are compliant with ethical principles for animal use and have been approved by the Animal Experiment Ethics Committee of Jinan University. In the present study, we established an animal model by intake of omega-6 PUFA combined acute myocardial ischemia to explore the mechanism of CHD. Intragastric administration of linoleic acid (LA) for 14 days, intraperitoneal injection of isoprenaline (ISO) was applied to induce acute myocardial ischemia for the animal model establishment. The animal ultrasound imaging system was used to detect cardiac function in vivo after ISO injection for 24 h. Serum and heart tissue samples were collected for the myocardial enzyme, phospholipidomics analysis and molecular biological detection. Compared to the LA group, the cardiac function showed that the left ventricular ejection fraction (EF%) and the left ventricular shortening fraction (FS%) decreased, aspaetate aminotransferase (AST), creatine kinase isoenzyme (CK-MB), and lactate dehydrogenase (LDH) increased in the LA + ISO mice. Compared to the ISO group, the phospholipidomics analysis showed that the PUFAs significantly were raised in the LA + ISO myocardium, and the content of oxidized phosphatidylethanolamine (ox-PE) changed most remarkable. Compared with the ISO group, the molecular biology detection showed that glutathione (GSH) and nicotinamide adenine dinucleotide phosphate (NADPH) were depleted, the end-products of ox-PE were increased, and the level of arachidonic acid 12/15-lipoxygenase (ALOX15) protein expression increased obviously. We suggest that ALOX15 mediated phospholipid peroxidation might be the critical mechanism of LA increased the susceptibility of myocardial ischemia injury. This study provides an experimental basis for whether PUFA could be used as an alternative treatment strategy for CHD prevention and provides a new intervention target for the early prevention strategy of CHD.

Application of add-on-design in post-marketing evaluation of traditional Chinese medicine / 中国中药杂志

Post-marketing evaluation of traditional Chinese medicine(TCM) is an important research stage in the life cycle of a drug, and the add-on-design is a common method for its post-marketing evaluation. This article introduces the basic concept of add-on-design, and points out that it is suitable for use based on the principles of medical ethics when the standard treatment should not be interrupted. The post-marketing evaluation of TCM should be carried out based on human experience and in compliance with regulations and ethics. The clinical values of TCM, such as the therapeutic effect for disease, improvement of disease symptoms, improvement in quality of life, as well as the synergism and toxicity attenuation of combined use of TCM and chemical drugs, should be fully reflected through the clinical trials designed with add-on-design. The key points of add-on-design are accurate clinical positioning, scientific estimation of sample size, and rigorous standard treatment. Standard treatment should be a recognized one, consistent and stable; appropriate and recognized efficacy indicators and targeted safety indicators should be selected; the design and operation of clinical research scheme should meet the requirements of randomization and blind method, with special emphasis on the production of qualified placebo. The add-on-design has the advantages that the rights and interests of the subjects are adequately protected. Besides, the research conclusions are easily put into clinical application. But there are also many difficulties, such as the influence of confounding bias, the "ceiling" effect of clinical efficacy, and the difficulty of interpretation of adverse events. Therefore, a rigorous research quality assu-rance system should be established, and the quality control of evaluation consistency of researchers should be emphasized to ensure strict quality control in the research process.

An Extreme Learning Machine Based on Artificial Immune System.

Extreme learning machine algorithm proposed in recent years has been widely used in many fields due to its fast training speed and good generalization performance. Unlike the traditional neural network, the ELM algorithm greatly improves the training speed by randomly generating the relevant parameters of the input layer and the hidden layer. However, due to the randomly generated parameters, some generated "bad" parameters may be introduced to bring negative effect on the final generalization ability. To overcome such drawback, this paper combines the artificial immune system (AIS) with ELM, namely, AIS-ELM. With the help of AIS's global search and good convergence, the randomly generated parameters of ELM are optimized effectively and efficiently to achieve a better generalization performance. To evaluate the performance of AIS-ELM, this paper compares it with relevant algorithms on several benchmark datasets. The experimental results reveal that our proposed algorithm can always achieve superior performance.

Alternate Mediterranean diet score is positively associated with skeletal muscle mass index in middle-aged adults.

Researches have suggested Mediterranean diet might lower the risk of chronic diseases, but data on skeletal muscle mass (SMM) are limited. This community-based cross-sectional study examined the association between the alternate Mediterranean diet score (aMDS) and SMM in 2230 females and 1059 males aged 40-75 years in Guangzhou, China. General information and habitual dietary information were assessed in face-to-face interviews conducted during 2008-2010 and 3 years later. The aMDS was calculated by summing the dichotomous points for the items of higher intakes of whole grain, vegetables, fruits, legumes, nuts, fish and ratio of MUFA:SFA, lower red meat and moderate ethanol consumption. The SMM of the whole body, limbs, arms and legs were measured using dual-energy X-ray absorptiometry during 2011-2013. After adjusting for potential covariates, higher aMDS was positively associated with skeletal muscle mass index (SMI, SMM/height2, kg/m2) at all of the studied sites in males (all P trend<0·05). The multiple covariate-adjusted SMI means were 2·70 % (whole body), 2·65 % (limbs), 2·50 % (arms) and 2·70 % (legs) higher in the high (v. low) category aMDS in males (all P<0·05). In females, the corresponding values were 1·35 % (P trend=0·03), 1·05, 0·52 and 1·20 %, (P trend>0·05). Age-stratified analyses showed that the favourable associations tended to be more pronounced in the younger subjects aged less than the medians of 59·2 and 62·2 years in females and males (P interaction>0·10). In conclusion, the aMDS shows protective associations with SMM in Chinese adults, particularly in male and younger subjects.

Greater Intake of Fruit and Vegetables Is Associated with Greater Bone Mineral Density and Lower Osteoporosis Risk in Middle-Aged and Elderly Adults.

OBJECTIVE: A few studies have suggested that the consumption of fruit and vegetables (FV) may benefit bone health, but limited data are available in Asian subjects. We examined the association between FV intake and bone mineral density (BMD) and osteoporosis in Chinese adults. METHODS: This population-based cross-sectional study involved 2083 women and 1006 men aged 40-75 years in Guangzhou, China. Habitual dietary data was collected from a 79-item food frequency questionnaire by face-to-face interviews. The BMD was measured for the whole body (WB), lumbar spine (LS), total hip (TH) and femur neck (FN) with dual-energy X-ray absorptiometry. RESULTS: After adjustment for potential covariates, we observed dose-dependent associations between total FV intake and BMD and osteoporosis risk. The mean BMD was higher in tertile 3 vs. tertile 1 by 1.33% (TH) and 1.31% (FN) for FV, and 1.10% (WB), 1.57% (TH), and 2.05% (FN) for fruit (all P-trends < 0.05). Significant beneficial associations with BMD at some sites were also found in most fruit categories but not in total vegetables or their subgroups. The odds ratios (95% confidence interval) of osteoporosis (T-score ≤ -2.5) in tertile 3 (vs. 1) were 0.73 (0.58-0.92), 0.37 (0.22-0.60), and 0.71 (0.52-0.97) for FV; 0.82 (0.66-1.03), 0.48 (0.30-0.77) and 0.89 (0.61-1.12) for fruit; and 0.80 (0.64-1.01), 0.57 (0.35-0.92) and 0.76 (0.55-1.05) for vegetables at the LS, TH, and FN, respectively. The favorable association between FV intake and the occurrence of osteoporosis was evident only in subjects with lower BMI (<24.0 kg/m2, P-trends < 0.05). CONCLUSIONS: Greater intake of FV was independently associated with a higher BMD and a lower presence of osteoporosis in middle-aged and elderly Chinese subjects with lower BMI. Fruit tended to have more contribution to the favorable association than vegetables.

Elevated Serum Uric Acid Is Associated with Greater Bone Mineral Density and Skeletal Muscle Mass in Middle-Aged and Older Adults.

BACKGROUND AND OBJECTIVE: Previous studies have suggested a positive link between serum uric acid (UA) and bone mineral density (BMD). In this study, we re-examined the association between UA and BMD and further explored whether this was mediated by skeletal muscle mass in a general Chinese population. METHOD: This community-based cross-sectional study was conducted among 3079 (963 men and 2116 women) Chinese adults aged 40-75 years. Face-to-face interviews and laboratory analyses were performed to determine serum UA and various covariates. Dual-energy X-ray absorptiometry was used to assess the BMD and appendicular skeletal muscle mass. The skeletal muscle mass index (SMI = ASM/Height(2), kg/m(2)) for the total limbs, arms, and legs was then calculated. RESULTS: The serum UA was graded and, in general, was significantly and positively associated with the BMD and muscle mass, after adjustment for multiple covariates in the total sample. Compared with participants in lowest quartile of UA, those participants in highest quartile showed a 2.3%(whole body), 4.1%(lumbar spine), 2.4%(total hip), and 2.0% (femoral neck) greater BMDs. The mean SMIs in the highest (vs. lowest) quartile increased by 2.7% (total), 2.5% (arm), 2.7% (leg) respectively. In addition, path analysis suggested that the favorable association between UA and BMD might be mediated by increasing SMI. CONCLUSION: The elevated serum UA was associated with a higher BMD and a greater muscle mass in a middle-aged and elderly Chinese population and the UA-BMD association was partly mediated by muscle mass.

Adherence to the Mediterranean diet is associated with a higher BMD in middle-aged and elderly Chinese.

Previous studies showed that better adherence to the Mediterranean diet (MD) is associated with lower risk of chronic diseases, but limited data are available on bone health. We investigated the association of the MD with bone mineral density (BMD) in Chinese adults. We included 2371 participants aged 40-75 years in this community-based cross-sectional study. Dietary information was assessed at baseline and a 3-year follow-up. Alternate Mediterranean diet (aMed) scores were calculated. BMD was determined at the second survey. After adjusting for potential covariates, higher aMed scores were positively and dose-dependently associated with BMD (all P-trends < 0.05). The BMD values were 1.94% (whole body), 3.01% (lumbar spine), 2.80% (total hip), 2.81% (femur neck), 2.62% (trochanter), and 2.85% (intertrochanter) higher in the quintile 5 (highest, vs. quintile 1) aMed scores for all of the subjects (all P-values < 0.05). Similar associations were found after stratifying by gender (P-interaction = 0.338-0.968). After excluding the five non-significant components of vegetables, legumes, fish, monounsaturated to saturated fat ratio, and alcohol intake from the aMed scores, the percentage mean differences were substantially increased by 69.1-150% between the extreme quintiles. In conclusion, increased adherence to the MD shows protective associations with BMD in Chinese adults.