Genetically Regulated Bilirubin and Risk of Non-alcoholic Fatty Liver Disease: A Mendelian Randomization Study

Mildly elevated serum bilirubin levels were reported to be associated with decreased risk of non-alcoholic fatty liver disease (NAFLD). Whether this is a causal relationship remains unclear. We tested the hypothesis that genetically elevated plasma bilirubin levels are causally related to reduce risk of NAFLD. A total of 403 eligible participants were enrolled. NAFLD was determined by liver ultrasonography. The uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) gene variants (UGT1A1*6 and UGT1A1*28) were genotyped through sequencing. We applied a Mendelian randomization approach to assess the effects of genetically elevated bilirubin levels on NAFLD. NAFLD was diagnosed in 19% of participants in our study (NAFLD = 76; Non-NAFLD = 327). The variants of UGT1A1*28 and UGT1A1*6 were strongly associated with increased total bilirubin (TB), direct bilirubin (DB), and indirect bilirubin (IB) levels (each P < 0.001). These two common variants explain 12.7% (TB), 11.4% (IB), and 10.2% (DB) of the variance in bilirubin levels, respectively. In logistic regression model, after multifactorial adjustment for sex, age, aminotransferase (ALT), white blood count (WBC), and body mass index (BMI), variant UGT1A1*28 (OR = 1.39; 95%CI: 0.614–3.170; P = 0.43) and UGT1A1*6 (OR = 1.64, 95%CI, 0.78–3.44; P = 0.19) genotypes were not significantly associated with the risk of NAFLD. Moreover, the plasma bilirubin level (TB, IB, and DB) were not significantly associated with the risk of NAFLD (P > 0.30). A Mendelian randomization analysis of the UGT1A1 variants suggests that bilirubin is unlikely causally related with the risk of NAFLD

The analysis of alphaâ 1â antitrypsin glycosylation with direct LCâ MS/MS

A liquid chromatographyâ tandem mass spectrometry (LCâ MS/MS)â based methodology has been developed to differentiate coreâ and antennaryâ fucosylated glycosylation of glycopeptides. Both the glycosylation sites (heterogeneity) and multiple possible glycan occupancy at each site (microheterogeneity) can be resolved via intact glycopeptide analysis. The serum glycoprotein alphaâ 1â antitrypsin (A1AT) which contains both coreâ and antennaryâ fucosylated glycosites was used in this study. Sialidase was used to remove the sialic acids in order to simplify the glycosylation microheterogeneity and to enhance the MS signal of glycopeptides with similar glycan structures. β1â 3,4 galactosidase was used to differentiate coreâ and antennaryâ fucosylation. Inâ source dissociation was found to severely affect the identification and quantification of glycopeptides with low abundance glycan modification. The settings of the mass spectrometer were therefore optimized to minimize the inâ source dissociation. A threeâ step mass spectrometry fragmentation strategy was used for glycopeptide identification, facilitated by pGlyco software annotation and manual checking. The collision energy used for initial glycopeptide fragmentation was found to be crucial for improved detection of oxonium ions and better selection of Y1 ion (peptide+GlcNAc). Structural assignments revealed that all three glycosylation sites of A1AT glycopeptides contain complex Nâ glycan structures: site Asn70 contains biantennary glycans without fucosylation; site Asn107 contains biâ , triâ and tetraâ antennary glycans with both coreâ and antennaryâ fucosylation; site Asn271 contains biâ and triâ antennary glycans with both coreâ and antennaryâ fucosylation. The relative intensity of coreâ and antennaryâ fucosylation on Asn107 was similar to that of the A1AT protein indicating that the glycosylation level of Asn107 is much larger than the other two sites.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/146302/1/elps6432_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/146302/2/elps6432.pd

Rapid and cyclic dust accumulation during MIS 2 in Central Asia inferred from loess OSL dating and grain-size analysis

Due to lack of reliable proxies from the Westerlies-dominant region, the strength change of Northern Hemisphere Westerlies remains poorly understood. The aim of this study is to provide a reliable paleoclimatic proxy about the Northern Hemisphere Westerlies change. Here we report a 30.7 m thick loess section from the Ili basin directly controlled by the Westerlies. Based on optically stimulated luminescence (OSL) and high resolution grain-size records, we reconstruct the change history of the Westerlies strength during the last glacial period (mainly Marine Isotope Stages 2, MIS2), being similar with the Westerlies index recorded in the Qinghai Lake sediments. Within error limits, all ages are in stratigraphic order. We further compare the climatic records among the Ili loess, Qinghai Lake and the NGRIP, their similarity shows a good climatic coupling relationship among the Central Asia, East Asia and the North Atlantic, and the Westerlies plays a critical influence in transporting the North Atlantic signal to Central and East Asia

Rapid and cyclic dust accumulation during MIS 2 in Central Asia inferred from loess OSL dating and grain-size analysis

Due to lack of reliable proxies from the Westerlies-dominant region, the strength change of Northern Hemisphere Westerlies remains poorly understood. The aim of this study is to provide a reliable paleoclimatic proxy about the Northern Hemisphere Westerlies change. Here we report a 30.7 m thick loess section from the Ili basin directly controlled by the Westerlies. Based on optically stimulated luminescence (OSL) and high resolution grain-size records, we reconstruct the change history of the Westerlies strength during the last glacial period (mainly Marine Isotope Stages 2, MIS2), being similar with the Westerlies index recorded in the Qinghai Lake sediments. Within error limits, all ages are in stratigraphic order. We further compare the climatic records among the Ili loess, Qinghai Lake and the NGRIP, their similarity shows a good climatic coupling relationship among the Central Asia, East Asia and the North Atlantic, and the Westerlies plays a critical influence in transporting the North Atlantic signal to Central and East Asia

Luminescence age and palaeoenvironmental implications of a late Pleistocene ground wedge on the Northeastern Tibetan Plateau

A periglacial ground wedge in bajada gravel near the northern base of the Qinghai Nan Shan underlies loess of late- and postglacial age. The composition and structure of the wedge fill are consistent with an ice-wedge origin, implying former permafrost and relatively moist conditions at this locality. A luminescence date of 15,100±1600 years from the wedge fill marks the end of ice-wedge activity, which is inferred to have been during the last glaciation. The present mean annual air temperature (MAAT) (−0.7 °C) is too high to produce frost cracking and ice-wedge formation, but snowline depression of ca. 700-800 m in the adjacent mountains is consistent with a reduction in MAAT of at least 3.8°C during the last glacial maximum. Such a temperature depression would reduce MAAT to values equivalent to Arctic regions now experiencing active ice-wedge growth. The absence of loess of full-glacial age and the presence of a weakly developed palaeosol atop the bajada gravel imply a stable, cold land surface. Qinghai Lake, although reduced in size at that time, likely raised local humidity to levels that favoured ice-wedge growth in this low-altitude sector (ca. 3000-3400 m) of the Tibetan Plateau

Sex Differences in Outcomes among Stroke Survivors with Non-Valvular Atrial Fibrillation in China

Atrial fibrillation (AF) significantly increases the risk of stroke and disease burden and is an established predictor of poor outcomes after stroke. However, data regarding sex differences in long-term outcomes following stroke in patients with AF are scarce. We thus aimed to assess these differences. We recruited 951 consecutive patients with acute ischemic stroke and non-valvular atrial fibrillation (NVAF) treated at three hospitals in Tianjin, China, from January 2006 to September 2014. Information regarding stroke subtype, severity, risk factors, and outcomes (mortality, dependency, and recurrence) at 3, 12, and 36 months after stroke was recorded. The prevalence of NVAF was 8.4% overall, with a higher frequency in women than in men (11.3 vs. 6.9%, P < 0.001). Among patients with NVAF, women were older than men. Women were more likely than men to have severe stroke (38.8 vs. 29.5%, P < 0.001), high levels of total cholesterol and high- and low-density lipoprotein cholesterol (all P < 0.001), hypertension (69.1 vs. 61.2%, P = 0.012), dyslipidemia (29.8 vs. 20.7%, P = 0.001), and obesity (18.5 vs. 11.6%, P = 0.003); they were less likely than men to be current smokers (12.2 vs. 33.6%, P < 0.001) and to consume alcohol (0.9 vs. 13.9%, P < 0.001). There were greater risks of dependency and recurrence at 36 months after stroke in women than in men [odds ratios (95% confidence intervals), 1.64 (1.02–2.64) for dependency, P = 0.043; and 2.03 (1.28–3.20) for recurrence, P = 0.002] after adjustment for stroke subtype, severity, and risk factors. These findings suggest that it is crucial to emphasize the need for individualized stroke prevention education and promotion of healthy lifestyles in order to improve NVAF-related stroke outcomes and reduce disease burden in women

Sex differences in outcomes and associated factors among stroke patients with small artery occlusion in China

Abstract Background Sex differences in outcomes after small artery occlusion (SAO) stroke have not been well described, particularly in a Chinese population. We aimed to assess sex differences in outcomes and related risk factors among patients with SAO. Methods All consecutive patients with SAO were recruited between May 2005 and September 2014. Clinical features and risk factors were recorded. The mortality, recurrence, and dependency rates at 3 months after stroke were assessed. Results A total of 2524 patients with SAO were included in this study. There was a higher frequency of mild stroke, current smoking, and alcohol consumption in men than in women. Women were more likely than men to be older, to have diabetes and obesity, and to have higher total cholesterol, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol levels. There were worse outcomes in men than in women at 3 months after stroke (P < 0.05). There were more independent risk factors of poor outcome in men than in women. Older age was a common predictive factor of outcome both in men and in women. In men, low triglyceride levels and high fasting plasma glucose levels were independent risk factors for mortality; in addition, a high low-density lipoprotein cholesterol level was associated with recurrence. Moreover, in men, moderate and severe stroke, and high total cholesterol and fasting plasma glucose levels were risk factors for dependency. A negative association was found between low-density lipoprotein cholesterol level and risk of mortality and between total cholesterol level and risk of recurrence in women. Conclusions These findings suggest that it is crucial to control conventional risk factors and fasting plasma glucose and lipid levels among patients with SAO, especially male patients, to reduce the burden of stroke in China