[Association between cognitive function and probability of prodromal Parkinson's disease in middle aged and elderly people aged 55 years and above in 4 provinces in China].

Objective: To analyze probability of prodromal Parkinson's disease (pPD) and assess the association between global cognitive function and cognitive domain function and probability of pPD in ≥55 years old middle-aged and elderly people in Hebei, Zhejiang, Shaanxi and Hunan Provinces in China. Methods: Data were collected from dataset of the Community-based Cohort Study on Nervous System Disease 2020. We selected 4 634 Alzheimer disease and Parkinson's disease free persons aged ≥55 years with completed information on demographics, disease history, cognitive test, and risk factors of Parkinson's disease for this study. Cognitive function was assessed using Montreal Cognitive Assessment Scale (Chinese version). Calculation of probability of pPD and assessment of possible/probable pPD were performed according to the criteria published by the International Parkinson and Movement Disorder Society. Multivariate linear regression model was used to analyze the association between cognitive function and probability of pPD. Results: The M (Q1,Q3) of global cognitive function and cognitive domains in terms of memory, execution, visuospatial function, language, attention and orientation were 25 (20, 30), 13 (11, 15), 10 (7, 12), 6 (4, 7), 5 (4, 6), 15 (12, 18) and 6 (6, 6) points, respectively. The M(Q1,Q3) of probability of pPD was 0.42% (0.80%, 1.73%), and the proportion of the study subjects with possible/probable pPD was 0.4%. Differences in the distribution of probability of pPD were significant among groups by total cognitive score quartiles (P<0.001), and the difference in proportions of study subjects with possible/probable pPD was significant and showed decline trend (P=0.001). After adjusted for confounders, the results of multivariate linear regression analyses showed that probability of pPD in the Q2, Q3 and Q4 group decreased by 23.4%, 31.2% and 20.1% compared with Q1 group, and corresponding ß values were 0.766 (95%CI: 0.702-0.836), 0.688 (95%CI: 0.631-0.751) and 0.799 (95%CI: 0.730-0.875), respectively, the trend was significant (P<0.001). Higher index scores of execution, visuospatial function, language, attention and orientation were highly related to lower probability of pPD (P<0.001). Conclusion: Declines in global cognitive function and cognitive domains of execution, visuospatial function, language, attention and orientation might increase the probability of pPD in middle-aged and elderly people, suggesting the importance of cognitive intervention in early stage for pPD prevention.

[Relationship between nutrient-related dietary pattern and mild cognitive impairment in middle-aged and elderly people in 15 provinces of China].

Objective: To explore the relationship between nutrient-related dietary pattern and mild cognitive impairment (MCI) in middle-aged and elderly people. Methods: A total of 6 444 middle-aged and elderly people aged ≥55 years were selected in 2018 China Health and Nutrition Survey. MCI was evaluated by Mini-Mental State Examination, and the intakes of various foods were obtained by consecutive 3-day 24-hour dietary survey and weighing method. The intakes of various nutrients and total dietary energy were calculated based on the food composition table. Demographic and social information, lifestyle and health status of the respondents were obtained through questionnaire survey and physical measurements. In this study, vitamin C, vitamin E, zinc, iron, copper and selenium were selected as dependent variables. Nutrient-related dietary patterns were extracted by reduced rank regression method, and the relationship between dietary patterns and MCI was analyzed by multivariate logistic regression model. Results: Six dietary patterns were extracted in this study, and dietary pattern 1 with the highest explanatory degree was selected for subsequent analysis. Dietary pattern 1 was characterized by higher intakes of legume products, vegetables, fruits, nuts, pork, aquatic products and plant oil. Multivariate logistic regression analysis showed that the risk of MCI was lower in Q4 dietary score group than in Q1 dietary score group (OR=0.69, 95%CI: 0.49-0.98) in the 55-64 age group. In people with sleep duration of 8 hours per day, the risk of MCI was reduced in Q2, Q3 and Q4 dietary score groups compared with the Q1 dietary score group, with OR values of 0.68 (95%CI: 0.51-0.92), 0.67 (95%CI: 0.49-0.92) and 0.65 (95%CI: 0.45-0.92), respectively. Interaction analysis showed that the risk for MCI increased in those aged 65-74 years and ≥75 years compared with those aged 55-64 years in Q1 dietary score group. However, the risk for MCI decreased in both age groups as dietary pattern scores increased. Compared with those with sleep duration less or more than 8 hours per day in Q1 dietary score group, those with sleep duration of 8 hours per day in Q2 and Q3 dietary score groups had a reduced risk for MCI. Conclusion: Dietary patterns with higher intakes of legume products, vegetables, fruits, nuts, pork, aquatic products, and plant oil are negatively associated with MCI in people aged 55-64 years and those who slept 8 hours per day, and may reduce the risk of MCI with aging.

[Association between fasting plasma glucose and mild cognitive impairment in Chinese 55 and older population from four provinces].

Objective: To analyze the association of fasting plasma glucose (FPG) with mild cognitive impairment (MCI) in the Chinese middle-aged and elderly population from four provinces. Methods: Data were drawn from the baseline data of the Community-based Cohort Study on Nervous System Disease 2018-2019. We selected 3 272 subjects aged 55 and above with completed information on demographics, lifestyle, disease history, cognitive test, psychological assessment, and bio-chemistries measurement, and who were capable of performing basic activities of daily living but without Alzheimer's disease during recruitment. A multivariate logistic regression model was employed to analyze the association between FPG and MCI. Results: Median level of FPG in the study population was 5.5 mmol/L. The prevalence of MCI was 24.8%, and those in groups of the FPG quintile were 19.4%, 22.2%, 29.2%, 26.6%, and 26.1%, respectively, which significantly increased the trend (P=0.002). After adjustment of confounders, multivariate logistic regression analysis found that the MCI risk of subjects in the Q3,Q4 and Q5 groups was 1.641 (95%CI: 1.226-2.131), 1.373 (95%CI: 1.036-1.825), 1.402 (95%CI: 1.054-1.871) times as high as that in the Q1 group, respectively. Conclusion: High FPG level might serve as a risk factor for MCI in the middle-aged and elderly population, suggesting the importance of monitoring and controlling plasma glucose even without diabetes.

C-MYC-induced upregulation of LINC01503 promotes progression of non-small cell lung cancer.

OBJECTIVE: The purpose of this study was to detect the expression of long intergenic non-protein-coding RNA 1503 (LINC01503) in non-small cell lung cancer (NSCLC), and to further study its biological function, as well as the regulatory relationships of c-MYC with LINC01503 and the extracellular signal regulated kinase (ERK)/mitogen-activated protein kinase (MAPK) signaling pathway in NSCLC. PATIENTS AND METHODS: Tissue specimens were collected from 36 NSCLC patients, and the relative expression level of LINC01503 in the 36 cases of NSCLC tissue specimens and NSCLC cells was then determined using quantitative Reverse Transcription-Polymerase Chain Reaction (qRT-PCR). Then, the effects of LINC01503 on the proliferation and apoptosis of NSCLC cells were detected in vitro via Cell-Counting Kit (CCK)-8 assay, colony-forming assay and flow cytometry. Besides, the possible LINC01503 promoter-binding transcription factor was predicted using bioinformatics. After interference with c-MYC expression, the changes in the expression of LINC01503 were examined through qRT-PCR. Finally, the changes in the expressions of the molecular markers in the ERK/MAPK signaling pathway after interference with LINC01503 and c-MYC expressions were evaluated using Western blotting. RESULTS: According to qRT-PCR results, the expression of LINC01503 was upregulated in 30 out of 36 cases of NSCLC tissues. Compared with that in human normal bronchial epithelial cells, the expression of LINC01503 was elevated in NSCLC cells. As shown by the CCK-8 assay and colony-forming assay, the proliferation ability of NSCLC cells was weakened after interference with LINC01503 expression, and the flow cytometry results revealed the apoptosis rate of NSCLC cells was raised after interference with LINC01503 expression. Moreover, the bioinformatics prediction showed that c-MYC might be the LINC01503 promoter-binding transcription factor. Additionally, it was found through the qRT-PCR that the expression of LINC01503 declined after interference with c-MYC expression. Finally, based on Western blotting results, the expressions of phosphorylated ERK1/2 (p-ERK1/2) and p-MAPK/ERK kinase (MEK), the molecular markers in the ERK/MAPK signaling pathway, were inhibited after interference with c-MYC and LINC01503 expressions. CONCLUSIONS: The transcription factor c-MYC promotes the expression of LINC01503 in NSCLC and activates the ERK/MAPK signaling pathway to drive the development and progression of NSCLC.

[Dietary sodium intake of adult residents in 15 provinces of China in 2015].

Objective: To analyze the status of dietary sodium intake of Chinese adult residents in fifteen provinces in 2015. Methods: Data were collected from 2015 China Nutrition Transition Cohort Study. This cohort study used a three consecutive 24-h retrospective method to record food intake and weighing method to record household condiment consumption. In this study, 14 847 residents aged 18 years and over with complete data from 15 provinces in 2015 were selected for the comparison of dietary sodium intake (median) with different characteristics. Results: Among the 14 847 residents, 47.1% were males, and the rural and northern residents accounted for 60.1% and 37.7%, respectively. Median sodium intake was 3 960.0 mg/d among residents in 2015. The sodium intake of males (4 272.1 mg/d) was higher than that of females (3 716.6 mg/d). Across age subgroups, sodium intake was highest among residents aged 45-59 years (4 257.0 mg/d; 18-44 years old, 3 867.1 mg/d; ≥60 years old, 3 799.0 mg/d). Sodium intake was higher in rural area (4 042.9 mg/d) than in urban area (3 866.8 mg/d), higher in north (4 229.2 mg/d) than in south (3 806.8 mg/d) (all P values <0.05). 11.8% of residents with dietary sodium intake were below 2 000 mg/d. The main sources of dietary sodium were condiments (79.4%), regular cooking foods (11.9%) and processed foods (8.7%). Among the condiments, the salt and soy sauce accounted for 63.6% and 10.4%, respectively. Conclusion: In 2015, Chinese adult residents had higher dietary sodium intake with gender and regional differences. Condiments were the main source of dietary sodium.

[Analysis on cardio-metabolic related risk factors in farmers of 15 provinces in China].

Objective: To analyze the prevalence and co-prevalence of cardio-metabolic related risk factors in farmers aged ≥18 years in China, to explore the influence of population economic factors on them. Methods: A total of 3 367 farmers, including fishermen or hunters, aged ≥18 years were selected as study subjects from the database of Nutritional Status and Health Transition of Chinese Residents Project in 2015. Basic information (age, gender), data on anthropometric (body height, weight and waist size), blood biochemical and socioeconomic (occupation, income, education level and living area) were included. According to the definition of the metabolic syndrome released by the International Diabetes Federation (IDF) in 2005, five cardio-metabolic risk factors appeared as central obesity, increased triglycerides, decreased HDL-C, increased blood pressure and increased plasma glucose. Co-prevalence of risk factors was defined as detecting 2 or more risk factors in a person at the same time. Multivariate logistic regression model was used to analyze the relationship between socioeconomic factors and metabolic risk factors. Results: In 3 367 framers of 15 provinces (autonomous region and municipality), the prevalence rates of central obesity, increased blood pressure, increased plasma glucose, increased triglycerides and decreased HDL-C were 51.8%, 59.0%, 17.0%, 25.5% and 38.7% respectively. Multivariate logistic regression analysis showed that the risks for central obesity (OR=3.69, 95%CI: 3.17-4.28) and decreased HDL-C (OR=3.28, 95%CI: 2.81- 3.82) were higher in women than in men, and the risks for increased blood pressure (OR=0.73, 95%CI: 0.63-0.84), increased blood glucose (OR=0.80, 95%CI: 0.67-0.97) were lower in women than in men. Age was positively correlated with the prevalence or co-prevalence of metabolic risk factors (trend P<0.05). Framers in western China had obviously lower risk for central obesity compared with farmers in central China. No significant correlation was found between farmers' income level, education level or the prevalence of metabolic risk factors. Conclusion: In 15 provinces of China, the prevalence of at least 1 kind of cardio-metabolic risk factor was found in 85.5% of the farmers, and the co-prevalence of cardio-metabolic risk factor was found in 60% of farmers. The prevalence and co-prevalence of cardio-metabolic risk factors were significantly associated with age and gender. It is suggested to take targeted nutritional intervention and health education according to the distribution characteristics of prevalence and co-prevalence of cardio-metabolic factors and strengthen the early prevention and control programs of the diseases.

Reciprocal regulation of miRNAs and piRNAs in embryonic development.

MicroRNAs (miRNAs) and piwi-interacting RNAs (piRNAs) are two classes of small noncoding RNAs, both of which play roles in regulating tissue development. It is unknown whether these distinct classes of noncoding RNAs can regulate one another. Here we show that ectopic expression of miR-17 inhibited mouse fertility and early embryonic development. Specifically, we found that the piRNA amplification loop was repressed by miR-17-5p, leading to increased levels of transposition mutagenesis. This occurred by suppressing the amplification loop of piRNAs with an identical 5' sequence and by targeting Mili/Miwi2, an essential component of the piRNA amplification loop, and the DNA methyltransferase, Dnmt3a. We also found that increased levels of piRNAs could compete with miRNAs for target binding, resulting in increased expression of Dnmt3a and Mili. Increased Dnmt3a levels could in turn block miR-17-5p expression, while increased Mili expression could accelerate piRNA amplification and inhibit transposon generation, favoring embryonic development. We report for the first time the reciprocal regulation between miRNAs and piRNAs in mouse embryonic development.

Foxo3 activity promoted by non-coding effects of circular RNA and Foxo3 pseudogene in the inhibition of tumor growth and angiogenesis.

It has recently been shown that the upregulation of a pseudogene specific to a protein-coding gene could function as a sponge to bind multiple potential targeting microRNAs (miRNAs), resulting in increased gene expression. Similarly, it was recently demonstrated that circular RNAs can function as sponges for miRNAs, and could upregulate expression of mRNAs containing an identical sequence. Furthermore, some mRNAs are now known to not only translate protein, but also function to sponge miRNA binding, facilitating gene expression. Collectively, these appear to be effective mechanisms to ensure gene expression and protein activity. Here we show that expression of a member of the forkhead family of transcription factors, Foxo3, is regulated by the Foxo3 pseudogene (Foxo3P), and Foxo3 circular RNA, both of which bind to eight miRNAs. We found that the ectopic expression of the Foxo3P, Foxo3 circular RNA and Foxo3 mRNA could all suppress tumor growth and cancer cell proliferation and survival. Our results showed that at least three mechanisms are used to ensure protein translation of Foxo3, which reflects an essential role of Foxo3 and its corresponding non-coding RNAs.

Dietary patterns and their associations with general obesity and abdominal obesity among young Chinese women.

BACKGROUND/OBJECTIVES: Dietary patterns represent the combined effects of foods and efficaciously illustrate the impact of diet on health outcomes. This study identified the dietary patterns and determined their relationships with obesity among young Chinese women. SUBJECTS/METHODS: In 2011, the China Health and Nutrition Survey included 2363 young women aged 18-44 years. Factor analysis of data from three consecutive 24-h dietary recalls identified the dietary patterns. Weight, height and waist circumstance (WC) were measured, and body mass index (BMI) was calculated. General obesity was defined as BMI ⩾28 kg/m(2) and abdominal obesity as WC ⩾85 cm. RESULTS: Four dietary patterns were identified: traditional south; traditional north; snack; and high protein. After adjusting for confounders and energy intake, women in the highest-score quintiles of the traditional south pattern were less likely to have general obesity (odds ratio (OR)=0.48; 95% confidence interval (CI) 0.29-0.78) and abdominal obesity (OR=0.64; 95% CI 0.46-0.90). Subjects in the highest-score quintiles of the traditional north pattern had significantly greater risk of general obesity (OR=2.28; 95% CI 1.38-3.74) and of abdominal obesity (OR=2.32; 95% CI 1.66-3.24). CONCLUSION: The traditional south pattern of rice as the major staple food with pork and vegetable dishes is associated with lower risk of general and abdominal obesity. The traditional north pattern of high intake of wheat, other cereals and tubers is positively associated with general and abdominal obesity. This provides important information for interventions and policies addressing obesity prevention among young Chinese women.

Secular trends in meat and seafood consumption patterns among Chinese adults, 1991-2011.

BACKGROUND/OBJECTIVES: Several studies have suggested differential health effects in relation to different meat composition in Western population. The purpose of the study was to examine secular trends in meat and seafood consumption patterns among Chinese adults between 1991 and 2011. SUBJECTS/METHODS: Our longitudinal data are from 21,144 adults aged 18-75 in the China Health and Nutrition Survey, prospective cohort study. We assessed the intakes of meat and subtypes with three 24-h dietary recalls. We conducted multilevel mixed-effect logistic and linear regression models to examine meat consumption dynamics. RESULTS: The proportions of Chinese adults who consumed red meat, poultry and seafood increased from 65.7% in 1991 to 86.1% in 2011, from 7.5 to 20.9% and from 27.4 to 37.8%, respectively. With rapid decrease in meat intakes since 2009, the intakes of total meat, red meat, poultry and seafood among their consumers were 86.7 g/day, 86.4 g/day, 71.0 g/day and 70.3 g/day in 2011, respectively, which were just slightly higher compared with those in 1991. Fatty fresh pork has been predominantly component of total meat overtime, which consituted 54.0% of total meat intake, 80.0% of fresh red meat intake and 98.7% of fatty fresh red meat intake in 2011. CONCLUSION: Over the past two decades, meat consumption patterns of Chinese adults have been characterized by having a predominant intake of fatty fresh pork, suboptimal intakes of seafood and increased proportion of adults having excessive intakes of red meat and poultry overtime.

miR-17 extends mouse lifespan by inhibiting senescence signaling mediated by MKP7.

Here we show that transgenic expression of miR-17 extends lifespan and inhibits cellular senescence. We propose that miR-17 acts as a critical regulator of cellular senescence and tumorigenesis. We demonstrate that miR-17 targets both ADCY5 and IRS1, upregulating the downstream signals MKP7, FoxO3, LC3B, and HIF1α, and downregulating mTOR, c-myc, cyclin D1, and JNK. Silencing either ADCY5 or IRS1 promoted autophagy and repressed cellular senescence and apoptosis. Repression of ADCY5 by miR-17 translocated membrane-bound RGS2 into the nucleus, promoting interactions of RGS2 with HIF1α and the MKP7 promoter, enhancing MKP7 transcription. ADCY5 repression by miR-17 also facilitated the translocation of EGFR and MKP7 from membrane into cytoplasmic and mitochondrial fractions. Importantly, we found that MKP7 inhibited senescence by dephosphorylating PRAS40 at Thr246 and mTOR at Ser2248, facilitating the interaction and loss of function of both molecules. Thus, the oncogenic miR-17 also acts pleiotropically to inhibit cellular senescence and extend longevity.

Trends in dietary fiber intake in Chinese aged 45 years and above, 1991-2011.

BACKGROUND/OBJECTIVES: To analyze the time trends in total dietary fiber (DF) intake, DF food sources and total DF intake per 1000 kcal (DF density) in Chinese adults aged 45 years and above in the past 20 years. SUBJECTS/METHODS: We used the data from the China Health and Nutrition Survey (CHNS) collected in 1991, 1993, 1997, 2000, 2004, 2006, 2009 and 2011. Adults who were aged 45 years and above were included in each round. Water-insoluble DF intake was calculated by substituting the water-insoluble DF content of each food in the Chinese Food Composition Table (FCT) for food intake. Total DF was calculated according to the convert index, which indicates the ratio between total DF and water-insoluble DF for each food group. RESULTS: The mean daily total DF intake in males was 19.5 g/day in 1991 and 19.4 g/day in 2011. In females, it was 17.5 g/day in 1991 and 17.6 g/day in 2011. DF density increased in both males and females from 2004 to 2011. It was 9.0 g/1000 kcal in males and 9.5 g/1000 kcal in females in 2011. The major food sources of water-insoluble DF were cereals and vegetables. Communities with different levels of urbanization showed different trends in total DF intake: decreased consumption (2.9 g) in residents of low-urbanization communities and increased consumption (3.1 g) in those of high-urbanization communities. CONCLUSION: The average total DF intake in Chinese adults aged 45 years and above remained at a stable level. DF density increased because of slight decrease in energy intake. More public health messages should be disseminated, especially to the residents of low-urbanization communities, so as to increase their daily DF intake to a level close to the recommended DF intake.

Dynamics of the Chinese diet and the role of urbanicity, 1991-2011.

China's food consumption patterns and eating and cooking behaviours changed dramatically between 1991 and 2011. Macronutrient composition has shifted towards fats, and protein and sodium intakes remain high and potassium intake low. The rapid decline in intake of coarse grains and, later, of refined grains and increases in intake of edible oils and animal-source foods accompanied by major eating and cooking behaviour shifts are leading to what might be characterized as an unhealthy Western type of diet, often based on traditional recipes with major additions and changes. The most popular animal-source food is pork, and consumption of poultry and eggs is increasing. The changes in cooking and eating styles include a decrease in the proportion of food steamed, baked, or boiled, and an increase in snacking and eating away from home. Prior to the last decade, there was essentially no snacking in China except for hot water or green tea. Most recently, the intake of foods high in added sugar has increased. The dietary shifts are affected greatly by the country's urbanization. The future, as exemplified by the diet of the three mega cities, promises major growth in consumption of processed foods and beverages.

MicroRNA miR-93 promotes tumor growth and angiogenesis by targeting integrin-ß8.

It has been reported that the miR-106b∼25 cluster, a paralog of the miR-17∼92 cluster, possesses oncogenic activities. However, the precise role of each microRNA (miRNA) in the miR-106b∼25 cluster is not yet known. In this study, we examined the function of miR-93, one of the microRNAs within the miR-106b∼25 cluster, in angiogenesis and tumor formation. We found that miR-93 enhanced cell survival, promoted sphere formation and augmented tumor growth. Most strikingly, when miR-93-overexpressing U87 cells were co-cultured with endothelial cells, they supported endothelial cell spreading, growth, migration and tube formation. In vivo studies revealed that miR-93-expressing cells induced blood vessel formation, allowing blood vessels to extend to tumor tissues in high densities. Angiogenesis promoted by miR-93 in return facilitated cell survival, resulting in enhanced tumor growth. We further showed that integrin-ß8 is a target of miR-93. Higher levels of integrin-ß8 are associated with cell death in tumor mass and in human glioblastoma. Silencing of integrin-ß8 expression using small interfering RNA promoted cell proliferation, whereas ectopic expression of integrin-ß8 decreased cell growth. These findings showed that miR-93 promotes tumor growth and angiogenesis by suppressing, at least in part, integrin-ß8 expression. Our results suggest that inhibition of miR-93 function may be a feasible approach to suppress angiogenesis and tumor growth.