Urban-rural disparities in the association between long-term exposure to high altitude and malnutrition among children under 5 years old: evidence from a cross-sectional study in Tibet.

OBJECTIVE: To assess urban-rural disparities in the association between long-term exposure to high altitude and malnutrition among children under 5 years old. DESIGN: A three-stage, stratified, cluster sampling was used to randomly select eligible individuals from July to October 2020. The data of participants, including demographic characteristics, altitude of residence, and nutritional status, were collected via questionnaire and physical examination. SETTING: Tibet, China. PARTICIPANTS: Children under 5 years old in Tibet. RESULTS: Totally, 1975 children under 5 years old were included in this study. We found that an additional 1000 m increase in altitude was associated with decreased Z-scores of height-for-age (ß = -0·23, 95 % CI: -0·38, -0·08), Z-scores of weight-for-age (ß = -0·24, 95 % CI: -0·39, -0·10). The OR for stunting and underweight were 2·03 (95 % CI: 1·51 to 2·73) and 2·04 (95 % CI: 1·38 to 3·02) per 1000 m increase in altitude, respectively; and OR increased rapidly at an altitude above 3500 m. The effects of long-term exposure to high altitudes on the prevalence of underweight in rural children were higher than that in urban children (P < 0·05). CONCLUSIONS: High-altitude exposure is tightly associated with malnutrition among children under 5 years old. Improving children's nutrition is urgently needed in areas above 3500 m, especially in rural ones.

Urban-rural differences in the association between long-term exposure to ambient particulate matter (PM) and malnutrition status among children under five years old: A cross-sectional study in China.

Background: The evidence regarding the relationship between postnatal exposure of air pollution and child malnutrition indicators, as well as the corresponding urban-rural disparities, is limited, especially in low-pollution area of low- and middle-income countries (LMICs). Therefore, our aim was to contrast the effect estimates of varying ambient particulate matter (PM) on malnutrition indicators between urban and rural areas in Tibet, China. Methods: Six malnutrition indicators were evaluated in this study, namely, Z-scores of height for age (HFA), Z-scores of weight for age (WFA), Z-scores of weight for height (WFH), stunting, underweight, and wasting. Exposure to particles with an aerodynamic diameter ≤2.5 micron (µm) (PM2.5), particles with an aerodynamic diameter ≤10 µm (PM10) and particles with an aerodynamic diameter between 2.5 and 10 µm (PMc) was estimated using satellite-based random forest models. Linear regression and logistic regression models were used to assess the associations between PM and the above malnutrition indicators. Furthermore, the effect estimates of different PM were contrasted between urban and rural areas. Results: A total of 2511 children under five years old were included in this study. We found long-term exposure to PM2.5, PMc, and PM10 was associated with an increased risk of stunting and a decreased risk of underweight. Of these air pollutants, PMc had the strongest association for Z-scores of HFA and stunting, while PM2.5 had the strongest association for underweight. The results showed that the odds ratio (OR) for stunting were 1.36 (95% confidence interval (CI) = 1.06 to 1.75) per interquartile range (IQR) microgrammes per cubic metre (µg/m3) increase in PM2.5, 1.80 (95% CI = 1.30 to 2.50) per IQR µg/m3 increase in PMc and 1.55 (95% CI = 1.17 to 2.05) per IQR µg/m3 increase in PM10. The concentrations of PM were higher in urban areas, and the effects of PM on malnutrition indicators among urban children were higher than those of rural children. Conclusions: Our results suggested that PM exposure might be an important trigger of child malnutrition. Further prospective researches are needed to provide important scientific literature for understanding child malnutrition risk concerning postnatal exposure of air pollutants and formulating synthetically social and environmental policies for malnutrition prevention.

The impact of ambient air pollution on hospital admissions, length of stay and hospital costs for patients with diabetes mellitus and comorbid respiratory diseases in Panzhihua, Southwest China.

Background: There is limited evidence on association between air pollutants and hospital admissions, hospital cost and length of stay (LOS) among patients with diabetes mellitus (DM) and comorbid respiratory diseases (RD), especially in low- and middle-income countries (LMICs) with low levels of air pollution. Methods: Daily data on RD-DM patients were collected in Panzhihua from 2016 to 2020. A generalised additive model (GAM) was used to explore the effect of air pollutants on daily hospital admissions, LOS and hospital cost. Attributable risk was employed to estimate RD-DM's burden due to exceeding air pollution exposure, using both 0 microgrammes per cubic metre (µg/m3) and WHO's 2021 air quality guidelines as reference. Results: For each 10 ug/m3 increase of particles with an aerodynamic diameter <2.5 micron (µm) (PM2.5), particles with an aerodynamic diameter <10 µm (PM10), sulfur dioxide (SO2), nitrogen dioxide (NO2) and ozone (O3), the admissions of RD-DM patients increased by 7.25% (95% CI = 4.26 to 10.33), 5.59% (95% CI = 3.79 to 7.42), 10.10% (95% CI = 7.29 to 12.98), 12.33% (95% CI = 8.82 to 15.95) and -2.99% (95% CI = -4.08 to -1.90); per 1 milligramme per cubic metre (mg/m3) increase of carbon monoxide (CO) corresponded to a 25.77% (95% CI = 17.88 to 34.19) increment for admissions of RD-DM patients. For LOS and hospital cost, the six air pollutants showed similar effect. Given 0 µg/m3 as the reference, NO2 showed the maximum attributable fraction of 32.68% (95% CI = 25.12 to 39.42%), corresponding to an avoidable burden of 5661 (95% CI = 3611 to 5860) patients with RD-DM. Conclusions: There is an association between PM2.5, PM10, SO2, NO2, and CO with increased hospital admissions, LOS and hospital cost in patients with RD-DM. Disease burden of RD-DM may be improved by formulating policies related to air pollutants exposure reduction, especially in LMICs with low levels of air pollution.

Health and economic impacts of ambient air pollution on hospital admissions for overall and specific cardiovascular diseases in Panzhihua, Southwestern China.

Background: The associations of ambient air pollution with hospital admissions (HAs) for overall and specific causes of cardiovascular diseases (CVDs), as well as related morbidity and economic burdens remain understudied, especially in low-pollution areas of low- and middle-income countries (LMICs). We evaluated the short-term effects of exposure to PM2.5 (particles with an aerodynamic diameter ≤2.5 µm), PM10 (particles with an aerodynamic diameter ≤10 µm), and SO2 (sulfur dioxide) on HAs for CVDs in Panzhihua, China, during 2016-2020, and calculated corresponding attributable risks and economic burden. Methods: We used a generalized additive model (GAM) while controlling for time trends, meteorological conditions, holidays, and days of the week to estimate the associations. The cost of illness (COI) method was adopted to further assess corresponding hospitalization costs and productivity losses. Results: A total of 27 660 HAs for CVDs were included in this study. PM10 and SO2 were significantly associated with elevated risks of CVDs hospitalizations. Each 10 µg/m3 increase in PM10 and SO2 at lag06 corresponded to an increase of 2.48% (95% confidence interval (CI) = 0.92%-4.06%), and 5.50% (95% CI = 3.09%-7.97%) in risk of HAs for CVDs, respectively. The risk estimates of PM10 and SO2 on CVD hospitalizations were generally robust after adjustment for other pollutants in two-pollutant models. We found stronger associations between air pollution (PM10 and SO2) and CVDs in cool seasons than in warm seasons. For specific causes of CVDs, significant associations of PM10 and SO2 exposure with cerebrovascular disease and ischaemic heart disease were observed. Using 0 µg/m3 as the reference concentrations, 11.91% (95%CI = 4.64%-18.56%) and 15.71% (95%CI = 9.30%-21.60%) of HAs for CVDs could be attributable to PM10 and SO2, respectively. During the study period, PM10 and SO2 brought 144.34 million Yuan economic losses for overall CVDs, accounting for 0.028% of local GDP. Conclusions: Our results suggest that PM10 and SO2 exposure might be an important trigger of HAs for CVDs and accounted for substantial morbidity and economic burden.

Herbal Compounds with Special Reference to Gastrodin as Potential Therapeutic Agents for Microglia Mediated Neuroinflammation.

BACKGROUND: Activated microglia play a pivotal role neurodegenerative diseases by producing a variety of proinflammatory mediators including tumor necrosis factor-alpha (TNF-α), interleukin- 1beta (IL-1ß) and nitric oxide (NO) that are toxic to neurons and oligodendrocytes. METHODS: In view of the above, suppression of microglia mediated neuroinflammation is deemed a therapeutic strategy for neurodegenerative diseases. Several potential Chinese herbal extracts have been reported to exert neuroprotective effects against neurodegenerative diseases targeting specifically at the activated microglia. In this connection, the phenolic glucoside gastrodin, a main constituent of the Chinese herbal medicine Gastrodia rhizoma, produced widely in the local community exhibits potential neuroprotective effects through suppression of neurotoxic proinflammatory mediators. RESULTS: Here, we first review the roles of activated microglia in different brain diseases. The effects of gastrodin on activated microglia are then considered. We have identified gastrodin as a putative therapeutic agent as it has been found to suppress microglial activation thus ameliorating neuroinflammation. More importantly, gastrodin downregulates the expression of renin angiotensin system (RAS) and production of proinflammatory mediators. Remarkably, gastrodin promotes Sirtuin 3 (Sirt3) up-regulation and nicotinamide adenine dinucleotide phosphate oxidase-2 (NOX-2) down-regulation after ischemichypoxia in activated microglia mediated by AT1 or AT2 receptors which are angiotensin II receptors subtypes, indicating a possible molecular link between RAS and Sirt3 survival genes. CONCLUSION: This review summarizes the beneficial effects of gastrodin acting on activated microglia along with other herbal compounds. Its efficacy in neuroprotection is consistent with some common herbal products in China.

Association Between Genetic Variant in the Promoter of Pri-miR-34b/c and Risk of Glioma.

Growing evidence indicates that p53 can regulate the expression of miRNAs, particularly the miR-34 family members, which are described as potential tumor suppressors. Loss of miR-34 suppresses TP53-mediated cell death, whereas over expression of miR-34 induced apoptosis. The study designed to investigate the association between the pir-miR-34b/c rs4938723, TP53 Arg72Pro and the risk of glioma. We genotyped the two polymorphisms in175 glioma patients and 235 healthy controls using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and DNA sequencing assay. Association analysis showed that the CC genotype of the pir-miR-34b/c rs4938723 was associated with a significantly decreased risk of glioma compared to the TT genotype (CC vs. TT: adjusted OR = 0.43;95% CI, 0.21-0.87,P = 0.02). Moreover, a significant association between the patients with glioma and controls was also observed in a recessive model (OR = 0.41; 95% CI, 0.21-0.81, P = 0.007). In contrast, the CC genotype of the TP53 Arg72Pro was associated with a significantly increased risk of glioma compared to the GG genotype (CC vs. GG: adjusted OR = 1.73;95% CI, 1.04-2.89,P = 0.04), and a significant association between the patients with glioma and controls was also observed in a recessive model (OR = 2.00; 95% CI, 1.26-3.18, P = 0.003). These findings suggest that the pri-miR-34b/c rs4938723CC and TP53 Arg72-Pro polymorphisms may be associated with the risk of glioma.

Gastrodin attenuates microglia activation through renin-angiotensin system and Sirtuin3 pathway.

Microglia activation and its mediated production of proinflammatory mediators play important roles in different neurodegenerative diseases; hence, modulation of microglia activation has been considered a potential therapeutic strategy to ameliorate neurodegeneration. This study was aimed to determine whether Gastrodin, a common herbal agent known to possess neuroprotective property, can attenuate production of proinflammatory mediators in activated microglia through the renin-angiotensin system (RAS) and Sirtuin3 (SIRT3). Expression of various members of the RAS including ACE, AT1, AT2, and SIRT3 in activated microglia was assessed by immunofluorescence and Western blot in hypoxic-ischemia brain damage (HIBD) in postnatal rats, and in BV-2 microglia in vitro challenged with lipopolysaccharide (LPS) with or without Gastrodin treatment. Expression of NOX-2, a subunit of NADPH oxidase, and proinflammatory mediators including iNOS and TNF-α, was also evaluated. The present results showed that expression of ACE, AT1, NOX-2, iNOS and TNF-α was markedly increased in activated microglia in the corpus callosum of HIBD rats, and in LPS stimulated BV-2 microglia. Remarkably, the expression was markedly attenuated following Gastrodin treatment. Conversely, Gastrodin enhanced AT2 and SIRT3 protein expression. In BV-2 microglia treated with Azilsartan, a specific inhibitor of AT1 (AT1I group), NOX-2 expression was decreased whereas that of SIRT3 in LPS + AT1I and LPS + Gastrodin group was increased when compared with the controls. In LPS + AT1I + Gastrodin group, SIRT3 expression was further augmented. More importantly, Gastrodin effectively reduced caspase 3 protein expression level in the HIBD rats coupled with a significant decrease in caspase 3 positive cells. We conclude that Gastrodin can exert its protective effects against the hypoxic-ischemia brain damage in the present experimental HIBD model. It is suggested that this is mainly through suppression of expression of RAS (except for AT2 and SIRT3) and proinflammatory mediators e.g. TNF-α in activated microglia.

Expression of SIRT3 in various glial cell types in the periventricular white matter in the neonatal rat brain after hypoxia.

Sirtuin 3 (SIRT3) mediates cellular resistance toward various forms of stress. SIRT3 expression in the developing brain, especially its localization in various glial cell types, has not been fully explored. This study aimed to determine SIRT3 expression in the brain of neonatal rats subjected to hypoxia. By immunohistochemistry, immunofluorescence and Western blotting, we show here that SIRT3 expression in the periventricular white matter was up-regulated in hypoxia group compared with the control group at the corresponding time points. Intense SIRT3 expression was detected in microglia at early time points after hypoxia whose cell number was increased with reduced ramifications in hypoxia group compared with the control group. Furthermore, SIRT3 immunoreactivity was obviously enhanced at 24 h, 3 and 7d, but was declined at 14d after hypoxia so that SIRT3 expression between the two groups was comparable. SIRT3 immunofluorescence was also localized in astrocytes labeled with GFAP which was augmented at different time points in hypoxia group. GPAP positive astrocytes exhibited long extending processes being most pronounced at 3d. SIRT3 was moderately expressed at 24 h, 3 and 7d, but was markedly increased at 14d after hypoxia. Moderate SIRT3 expression was also localized in oligodendrocytes labeled with CNPase in the control group. The incidence of CNPase positive oligodendrocytes showing colocalization of SIRT3 increased significantly at 24 h, 3 and 7d after hypoxia. In conclusion, SIRT3 expression was differentially up-regulated in all three major glial cell types following hypoxia. It is suggested that increased SIRT3 expression in the respective glial cell types following hypoxia is involved in different signaling pathways that protect against hypoxic stress in the developing brain.