Long-term exposure to fine particulate matter constituents in relation to chronic kidney disease: evidence from a large population-based study in China.

The effects of long-term exposure to fine particulate matter (PM2.5) constituents on chronic kidney disease (CKD) are not fully known. This study sought to examine the association between long-term exposure to major PM2.5 constituents and CKD and look for potential constituents contributing substantially to CKD. This study included 81,137 adults from the 2018 to 2019 baseline survey of China Multi-Ethnic Cohort. CKD was defined by the estimated glomerular filtration rate. Exposure concentration data of 7 major PM2.5 constituents were assessed by satellite remote sensing. Logistic regression models were used to estimate the effect of each PM2.5 constituent exposure on CKD. The weighted quantile sum regression was used to estimate the effect of mixed exposure to all constituents. PM2.5 constituents had positive correlations with CKD (per standard deviation increase), with ORs (95% CIs) of 1.20 (1.02-1.41) for black carbon, 1.27 (1.07-1.51) for ammonium, 1.29 (1.08-1.55) for nitrate, 1.20 (1.01-1.43) for organic matter, 1.25 (1.06-1.46) for sulfate, 1.30 (1.11-1.54) for soil particles, and 1.63 (1.39-1.91) for sea salt. Mixed exposure to all constituents was positively associated with CKD (1.68, 1.32-2.11). Sea salt was the constituent with the largest weight (0.36), which suggested its importance in the PM2.5-CKD association, followed by nitrate (0.32), organic matter (0.18), soil particles (0.10), ammonium (0.03), BC (0.01). Sulfate had the least weight (< 0.01). Long-term exposure to PM2.5 sea salt and nitrate may contribute more than other constituents in increasing CKD risk, providing new evidence and insights for PM2.5-CKD mechanism research and air pollution control strategy.

Association of Dietary Approaches to Stop Hypertension diet and Mediterranean diet with blood pressure in less-developed ethnic minority regions.

OBJECTIVE: We aimed to investigate the association of Dietary Approaches to Stop Hypertension (DASH)-style diet and Mediterranean-style diet with blood pressure in less-developed ethnic minority regions (LMERs). DESIGN: Cross-sectional study. SETTING: Dietary intakes were assessed by a validated food frequency questionnaire. Dietary quality was assessed by the DASH-style diet score and the alternative Mediterranean-style diet (aMED) score. The association between dietary quality and blood pressure was evaluated using multivariate linear regression model. We further examined those associations in subgroups of blood pressure level. PARTICIPANTS: A total of 81433 adults from the China Multi-Ethnic Cohort (CMEC) study were included in this study. RESULTS: In the overall population, compared with the lowest quintile, the highest quintile of DASH-style diet score was negatively associated with systolic BP (coefficient: -2.78, 95% CI: -3.15 to -2.41; P-trend<0.001), while the highest quintile of aMED score had a weaker negative association with systolic BP (coefficient: -1.43, 95% CI: -1.81 to -1.05; P-trend<0.001). Both dietary indices also showed a weaker effect on diastolic BP (coefficient for DASH-style diet: -1.06, 95% CI: -1.30 to -0.82; coefficient for aMED: -0.43, 95% CI: -0.68 to -0.19). In the subgroup analysis, both dietary indices showed a stronger beneficial effect on systolic BP in the hypertension group than in either of the other subgroups. CONCLUSION: Our results indicated that the healthy diet originating from Western developed countries can also have beneficial effects on blood pressure in LEMRs. DASH-style diet may be a more appropriate recommendation than aMED as part of a dietary strategy to control blood pressure, especially in hypertensive patients.

[Effects of dl-3n-butylphthalide on the expression of VEGF and bFGF in transient middle cerebral artery occlusion rats].

OBJECTIVE: To investigate the effect of dl-3n-butylphthalide (NBP) on the expression of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) in protein and mRNA levels in the treatment of cerebral infarction with transient middle cerebral artery occlusion (MCAO) in rats. METHODS: The model of transient MCAO was established using the suture method of Longa by blocking middle cerebral artery (MCA) with a nylon suture. The MCA blood flow was restored by the withdrawal of the nylon suture 2 h after occlusion. Sham-operated rats (n=20) were prepared in similar fashion, but without occlusion of the MCA. Operated rats were randomizely divided into 2 groups (n=20 for each): vehicle group rats were only administered vegetable oil 2 mL twice daily for 3 days and NBP group rats were administrated NBP 25 mg/kg twice daily for 3 days. The infarct volume and neurological deficit were determined by TTC staining and Longa's score. VEGF and bFGF protein and mRNA were detected by immunohistochemistry and in situ hybridization. RESULTS: NBP markedly inhibited the neurological deficit and reduced the infarct volumes as compare to vehicle group (P<0.05). NBP significantly upregulated VEGF and bFGF expression in both protein and mRNA levels in the peripheral infarct and hippocampus regions in contrast with sham-operated and vehicle group (P<0.05). CONCLUSION: NBP has protective effects for cerebral ischemia through upregulating the expression of VEGF and bFGF.

[Effects of dl-3-n-butylphthalide on expression of VEGF and bFGF in rat brain with permanent focal cerebral ischemia].

OBJECTIVE: To study the effects of dl-3n-butylphthalide (NBP) on the protein and mRNA expression of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) in rats brain with permanent middle cerebral artery occlusion (MCAO). METHODS: The model of permanent MCAO was established by using the suture method of Longa, with which the nylon suture was used to make rat middle cerebral artery (MCA) blocked. Sham-operated rats (n=20) were prepared in similar fashion, but without doing the closed occlusion of the MCA. Operated rats were randomizely divided into model control and NBP groups (n= 20 for each). By intragastric administration, sham-operated and model control group rats were given vegetable oil 2 mL twice daily for 3 days, and also NBP group rats were given NBP 25 mg/kg twice daily for 3 days. The infarct volume and neurological deficit scores were determined by tetrazolium chloride (TTC) staining and Longa's score separately. The protein and mRNA of VEGF and bFGF were detected by immunohistochemistry and in situ hybridization. RESULTS: NBP markedly inhibited the neurological deficit and reduced the infarct volumes as compared to model control group (P < 0.05). NBP significantly upregulated VEGF and bFGF expression in both protein and mRNA levels in the peripheral infarct and hippocampus regions in contrast with sham-operated and model control groups (P < 0.05). In the infarct core, the protein and mRNA levels of VEGF and bFGF did not show significantly any difference (P > 0.05). CONCLUSION: NBP can significantly reduce neurological deficit and infarction volume, and therefore may have protective effect for cerebral ischemia through upregulating the expression of VEGF and bFGF.

GCH1 plays a role in the high-altitude adaptation of Tibetans.

Tibetans are well adapted to high-altitude hypoxia. Previous genome-wide scans have reported many candidate genes for this adaptation, but only a few have been studied. Here we report on a hypoxia gene ( GCH1, GTP-cyclohydrolase I), involved in maintaining nitric oxide synthetase (NOS) function and normal blood pressure, that harbors many potentially adaptive variants in Tibetans. We resequenced an 80.8 kb fragment covering the entire gene region of GCH1 in 50 unrelated Tibetans. Combined with previously published data, we demonstrated many GCH1 variants showing deep divergence between highlander Tibetans and lowlander Han Chinese. Neutrality tests confirmed a signal of positive Darwinian selection on GCH1 in Tibetans. Moreover, association analysis indicated that the Tibetan version of GCH1 was significantly associated with multiple physiological traits in Tibetans, including blood nitric oxide concentration, blood oxygen saturation, and hemoglobin concentration. Taken together, we propose that GCH1 plays a role in the genetic adaptation of Tibetans to high altitude hypoxia.

EP300 contributes to high-altitude adaptation in Tibetans by regulating nitric oxide production.

The genetic adaptation of Tibetans to high altitude hypoxia likely involves a group of genes in the hypoxic pathway, as suggested by earlier studies. To test the adaptive role of the previously reported candidate gene EP300 (histone acetyltransferase p300), we conducted resequencing of a 108.9 kb gene region of EP300 in 80 unrelated Tibetans. The allele-frequency and haplotype-based neutrality tests detected signals of positive Darwinian selection on EP300 in Tibetans, with a group of variants showing allelic divergence between Tibetans and lowland reference populations, including Han Chinese, Europeans, and Africans. Functional prediction suggested the involvement of multiple EP300 variants in gene expression regulation. More importantly, genetic association tests in 226 Tibetans indicated significant correlation of the adaptive EP300 variants with blood nitric oxide (NO) concentration. Collectively, we propose that EP300 harbors adaptive variants in Tibetans, which might contribute to high-altitude adaptation through regulating NO production.