To identify susceptibility variants for hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC), we conducted a genome-wide association study by genotyping 440,794 SNPs in 355 chronic HBV carriers with HCC and 360 chronic HBV carriers without HCC, all of Chinese ancestry. We identified one intronic SNP (rs17401966) in KIF1B on chromosome 1p36.22 that was highly associated with HBV-related HCC and confirmed this association in five additional independent samples, consisting of 1,962 individuals with HCC, 1,430 control subjects and 159 family trios. Across the six studies, the association with rs17401966 was highly statistically significant (joint odds ratio = 0.61, P = 1.7 x 10(-18)). In addition to KIF1B, the association region tagged two other plausible causative genes, UBE4B and PGD. Our findings provide evidence that the 1p36.22 locus confers susceptibility to HBV-related HCC, and suggest that KIF1B-, UBE4B- or PGD-related pathways might be involved in the pathogenesis of this malignancy.

BackgroundDyslipidemia is a modifiable risk factor for cardiovascular disease (CVD). We investigated the prevalence and associated risk factors of dyslipidemia- raised total cholesterol (TC), raised triglycerides (TG), raised low-density lipoprotein (LDL-C), low high-density lipoprotein (HDL-C), and raised non-high-density lipoprotein (non-HDL-C) in rural and urban China.MethodsWe analyzed data from 136,945 participants aged 40–100 years of the CNSSPP project for 2014. Dyslipidemia was defined by the NCEP-ATP III and the 2016 Chinese guidelines for the management of dyslipidemia in adults. Complete data on demographic, metabolic and lifestyle characteristics were used. Chi-square tests and multivariable logistic regression were used to obtain age- and sex-adjusted prevalence and risk factors for dyslipidemia among participants.ResultsA total of 53.1% participants lived in rural areas. The prevalence of dyslipidemia was similar among rural and urban participants (43.2% vs. 43.3%). Regarding the components of dyslipidemia: urban compared with rural participants had a higher prevalence of low HDL-C (20.8% vs. 19.2%), whereas the prevalence of raised LDL-C (7.8% vs. 8.3%), raised TC (10.9% vs.11.8%) and raised non-HDL-C (10.0% vs. 10.9%) were lower in urban residents, (all p < 0.001). Women were more likely to have raised TC than men (adjusted OR [AOR] =1.83, 95% confidence interval [CI]:1.75–1.91), raised LDL-C (AOR = 1.55, 95% CI: 1.47–1.63) and high non-HDL-C (AOR = 1.52 95% CI: 1.45–1.59) (all p < 0.001). Compared with rural, urban participants had higher odds of dyslipidemia: low HDL-C (AOR = 1.04, 95% CI: 1.01–1.07), and raised TG (AOR = 1.06, 95% CI: 1.04–1.09). Hypertension and current drinker were less likely to get low HDL-C with AOR 0.93 (95% CI: 0.90–0.96) and AOR 0.73 (95% CI: 0.70–75), respectively. Overweight, obesity, central obesity and diabetes had higher odds of all dyslipidemias (p < 0.001).ConclusionsLow HDL-C was higher in urban areas, whereas the remaining dyslipidemia types were more common in rural areas. Dyslipidemia was more common in women in both areas of residence. Overweight, obesity, central obesity and diabetes were associated with dyslipidemias. The need to intensify intervention programs to manage dyslipidemia and risk factors should be prioritized.

In China, stroke is a major cause of mortality, and long-term physical and cognitive impairment. To meet this challenge, the Ministry of Health China Stroke Prevention Project Committee (CSPPC) was established in April 2011. This committee actively promotes stroke prevention and control in China. With government financial support of 838.4 million CNY, 8.352 million people from 536 screening points in 31 provinces have received stroke screening and follow-up over the last seven years (2012–2018). In 2016, the CSPPC issued a plan to establish stroke centers. To shorten the pre-hospital period, the CSPPC established a stroke center network, stroke map, and stroke “Green Channel” to create three 1-h gold rescue circles, abbreviated as “1-1-1” (onset to call time <1 h; pre-hospital transfer time < 1 h, and door-to-needle time < 1 h). From 2017 to 2018, the median door-to-needle time dropped by 4.0% (95% confidence interval (CI), 1.4–9.4) from 50 min to 48 min, and the median onset-to-needle time dropped by 2.8% (95% CI, 0.4–5.2) from 180 min to 175 min. As of 31 December 2018, the CSPPC has established 380 stroke centers in mainland China. From 1 November 2018, the CSPPC has monitored the quality of stroke care in stroke center hospitals through the China Stroke Data Center Data Reporting Platform. The CSPPC Stroke program has led to a significant improvement in stroke care. This program needs to be further promoted nationwide.

Little is known of the dynamics of centromeric DNA in polyploid plants. We report the sequences of two centromere-associated bacterial artificial chromosome clones from a Triticum boeoticum library. Both autonomous and non-autonomous wheat centromeric retrotransposons (CRWs) were identified, both being closely associated with the centromeres of wheat. Fiber-fluorescence in situ hybridization and chromatin immunoprecipitation analysis showed that wheat centromeric retrotransposons (CRWs) represent a dominant component of the wheat centromere and are associated with centromere function. CRW copy number showed variation among different genomes: the D genome chromosomes contained fewer copies than either the A or B genome chromosomes. The frequency of lengthy continuous CRW arrays was higher than that in either rice or maize. The dynamics of CRWs and other retrotransposons at centromeric and pericentromeric regions during diploid speciation and polyploidization of wheat and its related species are discussed.

and xueyongz@caas.net.cn). † These authors contributed equally to this work. SUMMARYThe physical map of the hexaploid wheat chromosome 3B was screened using centromeric DNA probes. A 1.1-Mb region showing the highest number of positive bacterial artificial chromosome (BAC) clones was fully sequenced and annotated, revealing that 96% of the DNA consisted of transposable elements, mainly long terminal repeat (LTR) retrotransposons (88%). Estimation of the insertion time of the transposable elements revealed that CRW (also called Cereba) and Quinta are the youngest elements at the centromeres of common wheat (Triticum spp.) and its diploid ancestors, with Quinta being younger than CRW in both diploid and hexaploid wheats. Chromatin immunoprecipitation experiments revealed that both CRW and Quinta families are targeted by the centromere-specific histone H3 variant CENH3. Immuno colocalization of retroelements and CENH3 antibody indicated that a higher proportion of Quinta than CRWs was associated with CENH3, although CRWs were more abundant. Long arrays of satellite repeats were also identified in the wheat centromere regions, but they lost the ability to bind with CENH3. In addition to transposons, two functional genes and one pseudogene were identified. The gene density in the centromere appeared to be between three and four times lower than the average gene density of chromosome 3B. Comparisons with related grasses also indicated a loss of microcollinearity in this region. Finally, comparison of centromeric sequences of Aegilops tauschii (DD), Triticum boeoticum (AA) and hexaploid wheat revealed that the centromeres in both the polyploids and diploids are still undergoing dynamic changes, and that the new CRWs and Quintas may have undertaken the core role in kinetochore formation.

Background and Purpose—Total homocysteine (tHcy) levels are associated with secondary vascular events and mortality after stroke. The aim of this study was to investigate whether tHcy levels in the acute phase of a stroke contribute to the recurrence of cerebro-cardiovascular events and mortality.Methods—A total of 3799 patients were recruited after hospital admission for acute ischemic stroke. Levels of tHcy were measured within 24 hours after primary admission. Patients were followed for a median of 48 months.Results—During the follow-up period, 233 (6.1%) patients died. After adjustment for age, smoking status, diabetes mellitus, and other cardiovascular risk factors, patients in the highest tHcy quartile (>18.6 μmol/L) had a 1.61-fold increased risk of death (adjusted hazard ratio [HR], 1.61; 95% confidence interval [CI], 1.03–2.53) compared with patients in the lowest quartile (≤10 μmol/L). Further subgroup analysis showed that this correlation was only significant in the large-artery atherosclerosis stroke subtype (adjusted HR, 1.80; 95% CI, 1.05–3.07); this correlation was not significant in the small-vessel occlusion subtype (adjusted HR, 0.80; 95% CI, 0.30–2.12). The risk of stroke-related mortality was 2.27-fold higher for patients in the third tHcy quartile (adjusted HR, 2.27; 95% CI, 1.06–4.86) and 2.15-fold more likely for patients in the fourth quartile (adjusted HR, 2.15; 95% CI, 1.01–4.63) than for patients in the lowest tHcy quartile. The risk of cardiovascular-related mortality and the risk of recurrent ischemic stroke were not associated with tHcy levels.Conclusions—Our findings suggest that elevated tHcy levels in the acute phase of an ischemic stroke can predict mortality, especially in stroke patients with the large-vessel atherosclerosis subtype.

Background The overall global burden of stroke is considerable and increasing. In China, stroke is the leading cause of death and disability. Methods For this study, we used data from the National Stroke Screening Survey in 2012 and the 2010 Chinese population from sixth National Census of Populations to calculate a standardized (by age, gender, and education) stroke prevalence. Prevalence, risk factors, and management of stroke were compared by gender, age, and site. Findings The standardized prevalence rate of survival stroke patients in study population aged 60 and older was 4.94% in total. Hypertension was the most prevalent risk factor for stroke. Compared to men, women were more likely to have diabetes, obesity, elevated low-density lipoprotein cholesterol (LDL-C), and atrial fibrillation ( P < 0.05). Men were far more likely to drink and smoke than women ( P < 0.05). The rates of diabetes and atrial fibrillation were substantially higher in urban than those in rural stroke survivors ( P < 0.05). Rural stroke survivors exhibited higher rates of smoking and alcohol consumption than urban stroke survivors ( P < 0.05). Interpretation The stroke prevalence in China is in line with median worldwide stroke prevalence. Traditional risk factors remain highly prevalent in stroke survivors, among which hypertension was the most common. Stroke prevalence rates and risk factors varied by age, sex, and sociogeological factors. Electronic supplementary material The online version of this article (10.1007/s00415-019-09281-5) contains supplementary material, which is available to authorized users.

BackgroundCarotid atherosclerosis (CA) is a reflector of generalized atherosclerosis that is associated with systemic vascular disease. Data are limited on the epidemiology of carotid lesions in a large, nationally representative population sample. We aimed to evaluate the prevalence of CA detected by carotid ultrasonography and related risk factors based on a national survey in China.Methods and ResultsA total of 107 095 residents aged ≥40 years from the China National Stroke Prevention Project underwent carotid ultrasound examination. Participants with carotid endarterectomy or carotid stenting and those with stroke or coronary heart disease were excluded. Data from 84 880 participants were included in the analysis. CA was defined as increased intima–media thickness (IMT) ≥1 mm or presence of plaques. Of the 84 880 participants, 46.4% were men, and the mean age was 60.7±10.3 years. The standardized prevalence of CA was 36.2% overall, increased with age, and was higher in men than in women. Prevalence of CA was higher among participants living in rural areas than in urban areas. Approximately 26.5% of participants had increased IMT, and 13.9% presented plaques. There was an age‐related increase in participants with increased IMT, plaque presence, and stenosis. In multiple logistic regression analysis, older age, male sex, residence in rural areas, smoking, alcohol consumption, physical inactivity, obesity, hypertension, diabetes mellitus, and dyslipidemia were associated with CA.Conclusions CA was highly prevalent in a middle‐aged and older Chinese population. This result shows the potential clinical importance of focusing on primary prevention of atherosclerosis progression.