Matching actions to needs: shifting policy responses to the changing health needs of Chinese children and adolescents.

China is home to the second largest population of children and adolescents in the world. Yet demographic shifts mean that the government must manage the challenge of fewer children with the needs of an ageing population, while considering the delicate tension between economic growth and environmental sustainability. We mapped the health problems and risks of contemporary school-aged children and adolescents in China against current national health policies. We involved multidisciplinary experts, including young people, with the aim of identifying actionable strategies and specific recommendations to promote child and adolescent health and wellbeing. Notwithstanding major improvements in their health over the past few decades, contemporary Chinese children and adolescents face distinct social challenges, including high academic pressures and youth unemployment, and new health concerns including obesity, mental health issues, and sexually transmitted infections. Inequality by gender, geography, and ethnicity remains a feature of health risks and outcomes. We identified a mismatch between current health determinants, risks and outcomes, and government policies. To promote the health of children and adolescents in China, we recommend a set of strategies that target government-led initiatives across the health, education, and community sectors, which aim to build supportive and responsive families, safe communities, and engaging and respectful learning environments. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

Long-term effects of ambient PM2.5 constituents on metabolic syndrome in Chinese children and adolescents.

Metabolic syndrome (MetS) is considered a main public health issue as it remarkably adds the risk of cardiovascular disease, leading to a heavy burden of disease. There is growing evidence linking fine particulate matter (PM2.5) exposure to MetS. However, the influences of PM2.5 constituents, especially in children and adolescents, remain unclear. Our study was according to a national analysis among Chinese children and adolescents to examine the associations between long-term exposure to PM2.5 main constituents and MetS. A total of 10,066 children and adolescents aged 10-18 years were recruited in 7 provinces in China, with blood tests, health exams, and questionnaire surveys. We estimated long-term exposures to PM2.5 mass and its five constituents, containing black carbon (BC), organic matter (OM), inorganic nitrate (NO3-), sulfate (SO42-), and soil particles (SOIL) from multi-source data fusion models. Mixed-effects logistic regression models were used with the adjustment of a variety of covariates. In the surveyed populations, 2.9% were classified as MetS. From the single-pollutant models, we discovered that long-term exposures to PM2.5 mass, BC, OM, NO3-, as well as SO42-, were significantly associated with the prevalence of MetS, with odds ratios (ORs) per 1 µg/m3 that were 1.02 (95% confidence interval (CI): 1.01, 1.03) for PM2.5 mass, 1.24 (95% CI: 1.14, 1.35) for BC, 1.07 (95% CI: 1.04, 1.11) for OM, 1.09 (95% CI: 1.04, 1.13) for NO3-, and 1.14 (95% CI:1.04, 1.24) for SO42-. The influence of BC on the prevalence of MetS was robust in both the multi-pollutant model and the PM2.5-constituent joint model. The paper indicates long-term exposure to PM2.5 mass and specific PM2.5 constituents, particularly for BC, was significantly associated with a higher MetS prevalence among children and adolescents in China. Our results highlight the significance of establishing further regulations on PM2.5 constituents.

Associations of greenness surrounding schools with blood pressure and hypertension: A nationwide cross-sectional study of 61,229 children and adolescents in China.

BACKGROUND: Greenness exposure may lower blood pressure. However, few studies of this relationship have been conducted with children and adolescents, especially in low and middle-income countries. OBJECTIVES: To evaluate associations between greenness around schools and blood pressure among children and adolescents across China. METHODS: We recruited 61,229 Chinese citizens aged 6-18 years from 94 schools in a nationwide cross-sectional study in seven Chinese provinces/province-level municipalities. Participants' blood pressures and hypertension were assessed with standardized protocols. Greenness levels within 500 m and 1,000 m of each school were estimated with three satellite-based indices: vegetation continuous fields (VCF), normalized difference vegetation index (NDVI), and soil adjusted vegetation index (SAVI). Generalized linear mixed models were used to evaluate associations between greenness and blood pressure, greenness and prevalent hypertension, using coefficient and odds ratio respectively. Stratified analyses and mediation analyses were also performed. RESULTS: One interquartile range increase in greenness was associated with a 17%-20% reduced prevalence of hypertension for all measures of greenness (odds ratios for VCF500m = 20% (95% CI:18%, 23%); for NDVI500m = 17% (95% CI:13%, 21%); and for SAVI500m = 17% (95% CI: 13%, 20%). Increases in greenness were also associated with reductions in systolic blood pressure (0.48-0.58 mmHg) and diastolic blood pressure (0.26-0.52 mmHg). Older participants, boys, and urban dwellers showed stronger associations than their counterparts. No evidence of mediation was observed for air pollution (i.e., NO2 and PM2.5) and body mass index. CONCLUSION: Higher greenness around schools may lower blood pressure levels and prevalent hypertension among Chinese children and adolescents, particularly in older subjects, boys, and those living in urban districts. Further studies, preferably longitudinal, are needed to examine causality.

Status of school health programs in Asia: National policy and implementation.

BACKGROUND: The WHO's Health Promoting Schools (HPS) framework is based on an understanding of the reciprocal relationship between health and education, and the need to take a holistic approach to health promotion in schools. We aim to clarify the degree to which the HPS framework is reflected in the national policies of eight target countries and the issues surrounding its successful implementation. METHODS: Date were collected through two expert workshops with participants from eight Asian countries: Cambodia, China, Japan, Korea, Lao PDR, Nepal, the Philippines, and Thailand. In the first workshop, data collected on national policy were mapped against the HPS framework. From this, key issues were identified, and follow-up data collection was conducted in each country for a second workshop. RESULTS: We identified a policy shift toward the HPS framework in six out of the eight countries. Neither Japan nor Korea had changed their national policy frameworks to reflect an HPS approach; however, in the latter, model programs had been introduced at a local level. We identified various barriers to successful implementation, especially in relation to mental health and wellbeing. CONCLUSION: Given the recent shift toward the HPS approach in six out of the eight countries in this study, there is a need to conduct research to assess the impact of this framework on the health and wellbeing of students and school staff. At the same time, we call for more dialog in the context of Japan to explore the possible benefits of introducing the HPS framework into schools.

Time Trends in Cardiovascular Disease Mortality Across the BRICS: An Age-Period-Cohort Analysis of Key Nations With Emerging Economies Using the Global Burden of Disease Study 2017.

BACKGROUND: Brazil, Russia, India, China, and South Africa (BRICS) are emerging economies making up almost half the global population. We analyzed trends in cardiovascular disease (CVD) mortality across the BRICS and associations with age, period, and birth cohort. METHODS: Mortality estimates were derived from the Global Burden of Disease Study 2017. We used age-period-cohort modeling to estimate cohort and period effects in CVD between 1992 and 2016. Period was defined as survey year, and period effects reflect population-wide exposure at a circumscribed point in time. Cohort effects are defined as differences in risks across birth cohort. Net drift (overall annual percentage change), local drift (annual percentage change in each age group), longitudinal age curves (expected longitudinal age-specific rate), and period (cohort) relative risks were calculated. RESULTS: In 2016, there were 8.4 million CVD deaths across the BRICS. Between 1992 and 2016, the reduction in CVD age-standardized mortality rate in BRICS (-17%) was less than in North America (-39%). Eighty-eight percent of the increased number of all-cause deaths resulted from the increase in CVD deaths. The age-standardized mortality rate from stroke and hypertensive heart disease declined by approximately one-third across the BRICS, whereas ischemic heart disease increased slightly (2%). Brazil had the largest age-standardized mortality rate reductions across all CVD categories, with improvement both over time and in recent birth cohorts. South Africa was the only country where the CVD age-standardized mortality rate increased. Different age-related CVD mortality was seen in those ≥50 years of age in China, ≤40 years of age in Russia, 35 to 60 years of age in India, and ≥55 years of age in South Africa. Improving period and cohort risks for CVD mortality were generally found across countries, except for worsening period effects in India and greater risks for ischemic heart disease in Chinese cohorts born in the 1950s and 1960s. CONCLUSIONS: Except for Brazil, reductions of CVD mortality across the BRICS have been less than that in North America, such that China, India, and South Africa contribute an increasing proportion of global CVD deaths. Brazil's example suggests that prevention policies can both reduce the risks for younger birth cohorts and shift the risks for all age groups over time.

An integrative method based on UHPLC-Q-TOF-MS/MS combined with metabolomics to authenticate Isodon rubescens.

Genuine regional drugs have played a vital role in clinical use for a long time. There are differences in traditional Chinese medicines (TCM) from different regions based on their chemical composition. Differences in chemical composition may lead to deviations in therapeutic effects. To our knowledge, to date, there are no effective methods for distinguishing genuine regional drugs based on the differences in their chemical composition. Therefore, establishing an analytical platform for distinguishing the compounds used in TCM from various geographical locations is essential. In this work, an integrated platform based on UPLC-Q-TOF-MS/MS combined with plant metabolomics approach was established for comprehensively distinguishing genuine regional drugs. Isodon rubescens (Hemsl.) Hara, a widely used herbal medicine of China, was chosen for this study and 24 samples from four geographical locations in China were collected. A total of 60 ent-kaurane diterpenoids were tentatively identified, and then the samples from four geographical origins were distinguished using PCA (principal component analysis) and PLS-DA (partial least squares discrimination analysis). Different compounds were identified among the samples collected from the four geographical locations, and 12 of them were regarded as marker compounds responsible for the distinction. Our study highlights the essence and predictive ability of metabolomics in detecting minute differences in the same varieties of TCM samples based on the levels and compositions of their metabolites. These results showed that the analysis using UHPLC-Q-TOF-MS/MS combined with metabolomics could be applied to distinguish the geographical origins and varieties of TCM.

Greenness surrounding schools and adiposity in children and adolescents: Findings from a national population-based study in China.

BACKGROUND: Previous studies have indicated that exposure to green space may benefit human health. However, the available evidence concerning the effects of greenness, especially school-based greenness, on pediatric obesity is scarce. OBJECTIVE: To explore the association between school-based greenness and adiposity in children and adolescents in China. METHOD: We conducted a nationwide cross-sectional study of 56,620 children and adolescents (aged 6-18 years) in seven provinces/municipalities across China. School-based greenness was assessed using satellite-derived Normalized Difference Vegetation Index (NDVI) and Soil Adjusted Vegetation Index (SAVI) within 100-, 500-, and 1000-m circular buffers around each school's address. Generalized linear mixed regression models were used to estimate associations of greenness with BMI z-scores (zBMI), waist circumference, and prevalent overweight/obesity. We also explored the potential mediating role of ambient air pollution and physical activity in the greenness-adiposity associations. RESULT: In the adjusted model, an IQR increase in NDVI-1000m was associated with lower zBMI (ß: -0.11, 95% confidence interval[CI]: -0.13,-0.09) and waist circumference (ß: -0.64, 95%CI: -0.78,-0.50). Consistently, an IQR increase in NDVI-100m, NDVI-500m, NDVI-1000m was associated with 7-20% lower odds of overweight/obesity in the adjusted models. Air pollutants mediated 6.5-29.1% of the association between greenness and zBMI. No significant mediation effect was observed for physical activity. CONCLUSION: Higher school-based greenness levels were associated with lower zBMI, waist circumference, and lower odds of overweight and obesity in children and adolescents. Ambient air pollutants may partially mediate the greenness-adiposity associations.

Caprylic acid (C8:0) promotes bone metastasis of prostate cancer by dysregulated adipo-osteogenic balance in bone marrow.

Prostate cancer (PCa) continues to be the most common, noncutaneous cancer in men. Bone is the most frequent site of PCa metastases, and up to 90% of patients with advanced PCa develop bone metastases. An altered bone marrow microenvironment, induced by obesity, is a significant mediator for the bone tropism of PCa. However, the specific molecular mechanisms by which obesity causes changes in the bone marrow microenvironment, leading to PCa bone metastasis, are not fully understood. Our results demonstrate that a high-fat diet (HFD) leads to dyslipidemia and changes in bone marrow of nude mice: an increase in the area and number of adipocytes and a reduction in the area and number of osteoblasts. Moreover, a HFD promoted cyclooxygenase 2 (COX2) expression and inhibited osteoprotegerin (OPG) expression in the bone microenvironment. Additionally, the total level of free fatty acids (FFAs) and caprylic acid (C8:0) was significantly higher in PCa patients with bone metastases. In vitro, caprylic acid (C8:0) promoted bone mesenchymal stem cell (MSC)-derived adipocytic differentiation, COX2 expression, and prostaglandin E2 (PGE2) secretion, whereas osteoblastic differentiation and OPG expression were reduced. Furthermore, caprylic acid (C8:0)-treated adipocytes promoted the invasion and migration of PCa cells. Taken together, our findings suggest caprylic acid (C8:0) promotes bone metastasis of PCa by dysregulated adipo-osteogenic balance of bone marrow.

Body Mass Index Trajectory and Incident Hypertension: Results From a Longitudinal Cohort of Chinese Children and Adolescents, 2006-2016.

Objectives. To identify body mass index (BMI) trajectories in Chinese children and to compare the risk of incident high blood pressure (HBP) across trajectory groups.Methods. A total of 9286 children were included. The mean age at baseline was 8.9 years; age at endpoint ranged between 16 and 18 years. At least 8 measurements were obtained from each involved child. We used group-based trajectory modeling to identify BMI trajectory groups in each sex. We used blood pressure from each measurement to define HBP.Results. We identified 4 BMI trajectories for each sex. Compared with the low trajectory group, the hazard ratios of HBP in the higher trajectory groups ranged from 1.17 (95% confidence interval [CI] = 1.11, 1.23) to 2.00 (95% CI = 1.78, 2.27) during follow-up, and HBP risk at late adolescence ranged from 1.36 (95% CI = 1.22, 1.52) to 3.63 (95% CI = 3.12, 4.21). All trend P values across trajectories were less than .001. In terms of population level, overweight started 3 years earlier than HBP.Conclusions. Children of higher BMI trajectories had a higher risk of HBP during adolescence. The transition period from overweight to HBP onset could be critical for HBP prevention.

Serum FFAs profile analysis of Normal weight and obesity individuals of Han and Uygur nationalities in China.

BACKGROUND: Han and Uygur are the two main nationalities living in Xinjiang, China. There are significant differences in the incidence of metabolic diseases for two nationalities, but the specific reasons are not clear. Obesity is an important risk factor for the development of metabolic syndrome, which may be closely related to the increase of serum free fatty acids (FFAs) content. This study aims to use metabolomics to compare the changes of serum FFAs profiles between normal weight (NW) and obese (OB) individuals of two nationalities, screening out the differential FFAs, predicting and evaluating their relationship with diseases. METHODS: Thirty-four kinds of FFAs in serum were detected by ultra-high-pressure liquid chromatography-mass spectrometry (UHPLC-MS) and distinctions in FFAs profiles were evaluated using a metabolomics method while Receiver operating characteristics (ROC) and logistic regression models were used to explore FFAs significant for diagnosing obesity and obesity-associated comorbidities. RESULTS: In the Han nationality, ten kinds of FFAs (C7:0, C8:0, C9:0, C10:0, C11:0, C14:0, C18:2, C20:3, C20:4 and C22:6) showed significant differences between NW and OB individuals. These differential FFAs may be related to hypertension and gestational diabetes mellitus. In the Uygur nationality, C20:3 and C20:5 showed significant differences between NW and OB individuals. C9:0 and C19:0, which were screened out among the female subjects, showed a good ability to predict obesity status in Uygur females (AUC = 0.950). CONCLUSION: In both the Han and Uygur nationalities, the FFAs profiles of NW individuals differed from those of OB individuals. The significantly differential FFAs are closely related to obesity and may be important risk factors for obesity and related metabolic diseases.

Subnational variation of stunting, wasting and malnutrition in Chinese primary-school children between 2010 and 2014: urban-rural disparity.

OBJECTIVE: To examine urban-rural disparity in childhood stunting, wasting and malnutrition at national and subnational levels in Chinese primary-school children in 2010 and 2014. DESIGN: Data were obtained from two nationwide cross-sectional surveys conducted in 2010 and 2014. Malnutrition was classified using the Chinese national 'Screening Standard for Malnutrition of Children'. SETTING: All twenty-seven mainland provinces and four municipalities of mainland China.ParticipantsChildren aged 7-12 years (n 215 214; 107 741 in 2010 and 107 473 in 2014) from thirty-one provinces. RESULTS: Stunting, wasting and malnutrition prevalence were 1·9, 12·3 and 13·7 % in 2010, but decreased to 1·0, 9·4 and 10·2 % in 2014, respectively. The prevalence of stunting, wasting and malnutrition in both urban and rural children was higher in western provinces, while lower in eastern provinces. Although the prevalence of wasting and malnutrition was higher in rural children than their urban counterparts, the urban-rural disparity in both wasting and malnutrition decreased from 2010 to 2014 (prevalence OR: wasting, 1·35 to 1·16; malnutrition, 1·50 to 1·27). A reversal occurred in 2014 in several eastern provinces where the prevalence of wasting and malnutrition in urban children surpassed their rural peers. The urban-rural disparity was larger in western provinces than eastern provinces. CONCLUSIONS: The shrinking urban-rural disparity and the reversal in wasting and malnutrition suggest that the malnutrition situation has improved during the post-crisis period, especially in the western provinces. Region-specific policies and interventions can be useful to sustainably mitigate malnutrition in Chinese children, especially in rural areas and the western provinces.

Parental smoking and blood pressure in children and adolescents: a national cross-sectional study in China.

BACKGROUND: Current evidence on the health effects of passive smoking on childhood blood pressure is limited and inconsistent. We investigated the associations between exposure to parental smoking and blood pressure in children and adolescents. METHODS: A cross-sectional analysis was performed in a national sample of 42,745 children and adolescents (50.2% boys) aged 7-18 years from seven provinces in China. Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured. Information on parental smoking was collected through questionnaire. Multivariable linear regression and logistic regression was used to investigate the associations of parental smoking with blood pressure and prevalent hypertension, respectively. RESULTS: The reported parental smoking rates were 49.7 and 50.2% in boys and girls, respectively. After adjustment for a range of potential confounders, exposure to parental smoking was associated with 0.44 [95% confidence interval (CI): 0.16, 0.72] mmHg and 0.26 (95% CI: 0.04, 0.47) mmHg higher SBP and DBP in girls. Girls exposed to parental smoking were also more likely to have hypertension compared with those without exposure (odds ratio = 1.11, 95% CI: 1.02, 1.20). No significant associations were found in boys. CONCLUSIONS: Exposure to parental smoking was associated with increased blood pressure and higher prevalence of hypertension in girls, but not in boys. Urgent strategies are needed for the promotion of smoking-free environment, especially for children and adolescents.

Magnetic susceptibility increases as diamagnetic molecules breakdown: Myelin digestion during multiple sclerosis lesion formation contributes to increase on QSM.

BACKGROUND: The pathological processes in the first weeks of multiple sclerosis (MS) lesion formation include myelin digestion that breaks chemical bonds in myelin lipid layers. This can increase lesion magnetic susceptibility, which is a potentially useful biomarker in MS patient management, but not yet investigated. PURPOSE: To understand and quantify the effects of myelin digestion on quantitative susceptibility mapping (QSM) of MS lesions. STUDY TYPE: Histological and QSM analyses on in vitro models of myelin breakdown and MS lesion formation in vivo. POPULATION/SPECIMENS: Acutely demyelinating white matter lesions from MS autopsy tissue were stained with the lipid dye oil red O. Myelin basic protein (MBP), a major membrane protein of myelin, was digested with trypsin. Purified human myelin was denatured with sodium dodecyl sulfate (SDS). QSM was performed on phantoms containing digestion products and untreated controls. In vivo QSM was performed on five MS patients with newly enhancing lesions, and then repeated within 2 weeks. FIELD STRENGTH/SEQUENCE: 3D T 2 * -weighted spoiled multiecho gradient echo scans performed at 3T. ASSESSMENT: Region of interest analyses were performed by a biochemist and a neuroradiologist to determine susceptibility changes on in vitro and in vivo QSM images. STATISTICAL TESTS: Not applicable. RESULTS: MBP degradation by trypsin increased the QSM measurement by an average of 112 ± 37 ppb, in excellent agreement with a theoretical estimate of 111 ppb. Degradation of human myelin by SDS increased the QSM measurement by 23 ppb. As MS lesions changed from gadolinium enhancing to nonenhancing over an average of 15.8 ± 3.7 days, their susceptibility increased by an average of 7.5 ± 6.3 ppb. DATA CONCLUSION: Myelin digestion in the early stages of MS lesion formation contributes to an increase in tissue susceptibility, detectable by QSM, as a lesion evolves from gadolinium enhancing to nonenhancing. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2018;47:1281-1287.

Prevalence and risk factors of impaired fasting glucose and diabetes among Chinese children and adolescents: a national observational study.

The prevalence of impaired fasting glucose (IFG) and diabetes mellitus (DM) has reportedly increased significantly among Chinese children and adolescents. We aimed to examine the prevalence of IFG and DM, the disparities in sex and region and related risk factors among Chinese children and adolescents. A total of 16 434 Chinese children aged 6-17 years were selected from a national cross-sectional survey, and fasting glucose was measured for all participants. Overall, mean fasting plasma glucose (FPG) concentration was (4·64 (sd 0·51)) mmol/l, and the prevalence of DM and IFG was 0·10 and 1·89 %, respectively. Compared with girls, boys had higher FPG concentration (4·69 v. 4·58 mmol/l, r 0·107, P<0·001) and IFG prevalence (2·67 v. 1·07 %, r φ 0·059, P<0·001). Compared with rural children and adolescents, urban children and adolescent had higher FPG concentration (4·65 v. 4·62 mmol/l, r 0·029, P<0·001) and DM prevalence (0·15 v. 0·05 %, r φ 0·016, P<0·01). In addition, self-reported fried foods intake and overweight/obesity were positively associated with IFG, and the proportion of consuming fried foods more than or equal to once per week and overweight/obesity prevalence in boys and urban children and adolescents were significantly higher than girls and rural children and adolescents, respectively (P<0·05). Although the prevalence of IFG and DM was relatively low in Chinese children and adolescents, sex and region disparities were observed, which may be associated with differences in overweight/obesity prevalence and dietary factors.

Prevalence of excess body weight and underweight among 26 Chinese ethnic minority children and adolescents in 2014: a cross-sectional observational study.

BACKGROUND: Little is known regarding the nutritional burden in Chinese ethnic minority children. This study aimed to investigate the epidemiological characteristics of excess body weight and underweight for 26 ethnic groups. METHODS: Data on 80,821 participants aged 7-18 years across 26 minorities, with completed records from a large national cross-sectional survey, were obtained from Chinese National Survey on Students' Constitution and Health (CNSSCH) in 2014. Excess body weight, underweight and their components were classified according to Chinese national BMI references. RESULTS: The overall prevalence of excess body weight and underweight among ethnic groups were 12.0% and 14.5%, in which 4.4% and 4.1% of the participants were classified as obese and severe wasting, respectively. Compared with girls, boys showed a higher prevalence of underweight, severe wasting and obesity, but a lower prevalence of excess body weight (P < 0.05). Among 26 ethnic groups, Koreans had the highest prevalence of excess body weight (30.4%), while Bouyeis showed the highest prevalence of underweight (25.7%). The ethnic minority groups with high prevalence of excess body weight and underweight were more likely to show high burden of obesity and severe wasting, respectively. However, it is not the case for some groups, such as Miaos and Shuis. CONCLUSIONS: A worrying dual burden of excess body weight and underweight was recognized in Chinese ethnic minority children. Since various characteristics were found among different minorities, the ethnic-specific effort is warranted to improve their nutritional status.

The Myelin and Lymphocyte Protein MAL Is Required for Binding and Activity of Clostridium perfringens ε-Toxin.

Clostridium perfringens ε-toxin (ETX) is a potent pore-forming toxin responsible for a central nervous system (CNS) disease in ruminant animals with characteristics of blood-brain barrier (BBB) dysfunction and white matter injury. ETX has been proposed as a potential causative agent for Multiple Sclerosis (MS), a human disease that begins with BBB breakdown and injury to myelin forming cells of the CNS. The receptor for ETX is unknown. Here we show that both binding of ETX to mammalian cells and cytotoxicity requires the tetraspan proteolipid Myelin and Lymphocyte protein (MAL). While native Chinese Hamster Ovary (CHO) cells are resistant to ETX, exogenous expression of MAL in CHO cells confers both ETX binding and susceptibility to ETX-mediated cell death. Cells expressing rat MAL are ~100 times more sensitive to ETX than cells expressing similar levels of human MAL. Insertion of the FLAG sequence into the second extracellular loop of MAL abolishes ETX binding and cytotoxicity. ETX is known to bind specifically and with high affinity to intestinal epithelium, renal tubules, brain endothelial cells and myelin. We identify specific binding of ETX to these structures and additionally show binding to retinal microvasculature and the squamous epithelial cells of the sclera in wild-type mice. In contrast, there is a complete absence of ETX binding to tissues from MAL knockout (MAL-/-) mice. Furthermore, MAL-/- mice exhibit complete resistance to ETX at doses in excess of 1000 times the symptomatic dose for wild-type mice. We conclude that MAL is required for both ETX binding and cytotoxicity.

Identification and comparative oridonin metabolism in different species liver microsomes by using UPLC-Triple-TOF-MS/MS and PCA.

Oridonin (ORI) is an active natural ent-kaurene diterpenoid ingredient with notable anti-cancer and anti-inflammation activities. Currently, a strategy was developed to identify metabolites and to assess the metabolic profiles of ORI in vitro using ultra-high-performance liquid chromatography-Triple/time-of-flight mass spectrometry (UPLC-Triple-TOF-MS/MS). Meanwhile, the metabolism differences of ORI in the liver microsomes of four different species were investigated using a principal component analysis (PCA) based on the metabolite absolute peak area values as the variables. Based on the proposed methods, 27 metabolites were structurally characterized. The results indicate that ORI is universally metabolized in vitro, and the metabolic pathway mainly includes dehydration, hydroxylation, di-hydroxylation, hydrogenation, decarboxylation, and ketone formation. Overall, there are obvious inter-species differences in types and amounts of ORI metabolites in the four species. These results will provide basic data for future pharmacological and toxicological studies of ORI and for other ent-kauranes diterpenoids. Meanwhile, studying the ORI metabolic differences helps to select the proper animal model for further pharmacology and toxicological assessment.

Effects of Hyperbaric Oxygen Therapy on Inflammasome Signaling after Traumatic Brain Injury.

OBJECTIVE: Neuroinflammation plays an important role in secondary tissue damage after traumatic brain injury (TBI). Recently, the inflammasome-mediated inflammatory pathway has been observed in the inflammatory response of TBI. In this study, we investigated the influence of hyperbaric oxygen therapy (HBOT) on inflammasome activation after TBI. METHODS: The experimental mice were randomly divided into 4 groups as follows: sham-operated normobaric air (21% O2 at one absolute atmosphere), HBOT only, TBI + normobaric air and TBI + HBOT. Following the evaluation of motor deficits and brain edema, the expression of inflammasome components and effectors was measured by qRT-PCR and Western blotting. Moreover, alterations in IL-1ß, IL-18 and high-mobility group box 1 (HMGB1) were calculated by enzyme-linked immunosorbent assay at each time point after injury. RESULTS: HBOT improved motor score and reduced brain edema. Furthermore, it suppressed protein expression of inflammasome components and reduced the levels of IL-1ß and IL-18, accompanied by the reduction of HMGB1 in brain tissues and serum. CONCLUSION: These results suggest that HBOT may alleviate the inflammatory response after TBI by inhibiting the activation of inflammasome signaling.

Metabolic syndrome and its associated early-life factors in children and adolescents: a cross-sectional study in Guangzhou, China.

OBJECTIVE: The present study aimed to investigate the prevalence of metabolic syndrome (MetS) in 7- to 17-year-old children and adolescents in China and to examine the relationship between MetS and its associated early-life factors. DESIGN: Data were collected using a standard parent/guardian questionnaire in a face-to-face interview. Each participant underwent a complete anthropometric evaluation. MetS was defined according to the criteria of the International Diabetes Federation (IDF; 2007) for children and adolescents. SETTING: Guangzhou, a large city in South China, September 2013. SUBJECTS: A total of 1770 children and adolescents were enrolled in the study, including 913 girls (51·6%) and 857 boys (48·4%). RESULTS: The overall prevalence of MetS in children and adolescents was 1·1% (n 19), which was higher in boys (1·4%) than in girls (0·8%). Multivariate analysis indicated that high birth weight was significantly associated with abdominal obesity (OR=2·86; 95% CI 1·62, 5·06) and MetS (OR=3·61; 95% CI 1·33, 9·82). Furthermore, >6 months of maternal breast-feeding was inversely associated with MetS (OR=0·39; 95% CI 0·16, 0·98). CONCLUSION: Based on IDF criteria, the prevalence of MetS among southern Chinese children was significantly lower than that in other populations. High birth weight was significantly associated with abdominal obesity and MetS, and breast-feeding for longer than 6 months was inversely associated with MetS in South China.

Tissue plasminogen activator regulates Purkinje neuron development and survival.

The cerebellar cortex is centrally involved in motor coordination and learning, and its sole output is provided by Purkinje neurons (PNs). Growth of PN dendrites and their major synaptic input from granule cell parallel fiber axons takes place almost entirely in the first several postnatal weeks. PNs are more vulnerable to cell death than most other neurons, but the mechanisms remain unclear. We find that the homozygous nervous (nr) mutant mouse's 10-fold-increased cerebellar tissue plasminogen activator (tPA), a part of the tPA/plasmin proteolytic system, influences several different molecular mechanisms, each regulating a key aspect of postnatal PN development, followed by selective PN necrosis, as follows. (i) Excess endogenous or exogenous tPA inhibits dendritic growth in vivo and in vitro by activating protein kinase Cγ and phosphorylation of microtubule-associated protein 2. (ii) tPA/plasmin proteolysis impairs parallel fiber-PN synaptogenesis by blocking brain-derived neurotrophic factor/tyrosine kinase receptor B signaling. (iii) Voltage-dependent anion channel 1 (a mitochondrial and plasma membrane protein) bound with kringle 5 (a peptide derived from the excess plasminogen) promotes pathological enlargement and rounding of PN mitochondria, reduces mitochondrial membrane potential, and damages plasma membranes. These abnormalities culminate in young nr PN necrosis that can be mimicked in wild-type PNs by exogenous tPA injection into cerebellum or prevented by endogenous tPA deletion in nr:tPA-knockout double mutants. In sum, excess tPA/plasmin, through separate downstream molecular mechanisms, regulates postnatal PN dendritogenesis, synaptogenesis, mitochondrial structure and function, and selective PN viability.