[Genetic study of cardiovascular disease subtypes defined by International Classification of Diseases].

OBJECTIVE: To study the molecular connection among cardiovascular diseases (CVD) subtypes defined by the International Classification of Diseases (ICD) version 10 (ICD-10). METHODS: Both phenotypic data and genotypic data used in this study were obtained from the UK Biobank. A total of 380 083 participants aged between 40 and 69 years were included. Those without any cardiovascular disease (either no ICD-10 code at all or no ICD-10 code containing letter I) were assigned to the control group. The five CVD subtypes were: ischaemic heart diseases (IHD), pulmonary heart disease and diseases of pulmonary circulation (PHD), cerebrovascular diseases (CRB), diseases of arteries, arterioles and capillaries (AAC), diseases of veins, lymphatic vessels and lymph nodes, and diseases not elsewhere classified (VLL). We first performed a genome-wide association study (GWAS) for each of the five subtypes. We summarized novel loci using genome-wide significance threshold P=5×10-8. Next, we used linkage disequilibrium score regression (LDSC) method to assess genetic correlation among the five subtypes. Lastly, we applied mendelian randomization (MR) approach to assess the causal relationship among the subtypes. The particular software that we used was generalised summary-data-based mendelian randomisation (GSMR). RESULTS: Through GWAS, we identified hundreds of genome-wide significant SNPs: 672 for IHD, 241 for PHD, 31 for CRB, 48 for AAC, and 193 for VLL. By comparing with published literature, we found 28 novel loci, for PHD (n=14), CRB (n =7) and AAC (n =7). Eight of these 28 loci were rare, where the lead SNP had minor allele frequency (MAF) less than 1%. LDSC analyses indicated IHD had significant genetic correlation with VLL (P=2.52×10-7), PHD (P=3.77×10-3) and AAC (P=4.90×10-3), respectively. Bidrectional GSMR analyses showed that IHD had a positive causal relationship with VLL (P=7.40×10-5) and AAC (P=1.50×10-3), while reverse causality was not supported. CONCLUSION: This study adopted an innovative approach to study the molecular connection among CVD subtypes that are defined by ICD. We identified potentially positive genetic correlation and causal effects among some of these subtypes. Research along this line will provide scientific insights and serve as a guidance for future ICD standards.

Visceral adiposity index and cervical arterial atherosclerosis in northeast China: a population based cross-sectional survey.

BACKGROUND AND PURPOSE: The burden of cervical arterial atherosclerosis, which is an important risk factor of stroke, is huge in China. The visceral adiposity index (VAI) is a convenient index that is related to a series of metabolic abnormalities and a variety of diseases, including cerebrovascular diseases. This study aimed to explore the relationship between VAI and cervical arterial atherosclerosis. METHODS: This cross-sectional study used the multistage stratified random cluster sampling method to acquire a representative sample of residents aged ≥40 in the general population of northeast China. All participants completed a detailed questionnaire and provided blood samples. Cervical vascular ultrasound was performed by experienced ultrasound doctors. VAI was calculated by a well-established formula and analyzed by quartiles (Q1-Q4). RESULTS: A total of 3688 people aged ≥40 years who underwent cervical arterial ultrasound were finally included, amongst whom 3.2% had increased intima-media thickness (IMT), 48.6% had carotid plaque and 4.0% had cervical artery stenosis (CAS). After adjusting for several parameters, little statistical significance was found between VAI and increased IMT; compared with the VAI-Q1 group, the VAI-Q2, VAI-Q3 and VAI-Q4 groups were more likely to have CAS [odds ratio (OR) 2.01, 95% confidence interval (CI) 1.17-3.43; OR 1.82, 95% CI 1.05-3.15; OR 1.79, 95% CI 1.03-3.12] and the VAI-Q3 and VAI-Q4 groups were at greater risk of carotid plaque (OR 1.30, 95% CI 1.05-1.62; OR 1.34, 95% CI 1.07-1.67). CONCLUSIONS: The VAI was related to carotid plaque and CAS in the general population that is older than 40 years.

Association between Serum Uric Acid Level and Carotid Atherosclerosis in Chinese Individuals Aged 75 Years or Older: A Hospital-Based Case-Control Study.

OBJECTIVES: To investigate the association between serum uric acid level and the presence and progression of carotid atherosclerosis in Chinese individuals aged 75 years or older. DESIGN: Case-control study. SETTING: In a teaching hospital. PARTICIPANTS: Five hundred and sixty-four elderlies (75 years or above) who underwent general health screening in our hospital were enrolled. MEASUREMENTS: The detailed carotid ultrasound results, physical examination information, medical history, and laboratory test results including serum uric acid level were recorded, these data were used to analyze the relationship between serum uric acid level and carotid atherosclerosis. Then, subjects who underwent the second carotid ultrasound 1.5-2 years later were further identified to analyzed the relationship between serum uric acid and the progression of carotid atherosclerosis. RESULTS: A total of 564 subjects were included, carotid plaque was found in 482 (85.5%) individuals. Logistic regression showed that subjects with elevated serum uric acid (expressed per 1 standard deviation change) had significantly higher incidence of carotid plaque (odds ratio, 1.37; 95% confidence interval, 1.07-1.75; P= 0.012) after controlling for other factors. A total of 236 subjects underwent the follow-up carotid ultrasound. Linear regression showed that serum uric acid level (expressed per 1 standard deviation change; 1 standard deviation = 95.5 µmol/L) was significantly associated with percentage of change of plaque score (P = 0.008). Multivariable linear regression showed that 1 standard deviation increase in serum uric acid levels was expected to increase 0.448% of plaque score (P = 0.023). CONCLUSION: The elevated serum uric acid level may be independently and significantly associated with the presence and progression of carotid atherosclerosis in Chinese individuals aged 75 years or older.

Broadband nonlinear optical response in multi-layer black phosphorus: an emerging infrared and mid-infrared optical material.

Black phosphorous (BP), the most thermodynamically stable allotrope of phosphorus, is a high-mobility layered semiconductor with direct band-gap determined by the number of layers from 0.3 eV (bulk) to 2.0 eV (single layer). Therefore, BP is considered as a natural candidate for broadband optical applications, particularly in the infrared (IR) and mid-IR part of the spectrum. The strong light-matter interaction, narrow direct band-gap, and wide range of tunable optical response make BP as a promising nonlinear optical material, particularly with great potentials for infrared and mid-infrared opto-electronics. Herein, we experimentally verified its broadband and enhanced saturable absorption of multi-layer BP (with a thickness of ~10 nm) by wide-band Z-scan measurement technique, and anticipated that multi-layer BPs could be developed as another new type of two-dimensional saturable absorber with operation bandwidth ranging from the visible (400 nm) towards mid-IR (at least 1930 nm). Our results might suggest that ultra-thin multi-layer BP films could be potentially developed as broadband ultra-fast photonics devices, such as passive Q-switcher, mode-locker, optical switcher etc.

Relationship between endothelial nitric oxide synthase gene polymorphisms and ischemic stroke: a meta-analysis.

OBJECTIVES: Previous studies examining whether polymorphisms (G894T, 4b/a, and T786C) in the endothelial nitric oxide synthase (eNOS) gene are associated with ischemic stroke have yielded conflicting results. We performed a meta-analysis to investigate the potential association between these three eNOS gene polymorphisms and ischemic stroke risk. MATERIALS AND METHODS: We searched databases until April 30, 2012 and used fixed or random effects models to estimate the pooled odds ratios (ORs). RESULTS: We analyzed 34 case-control data sets from 33 publications involving 5261/5823 cases/controls for G894T, 4295/4682 for 4b/a, and 2698/3254 for T786C polymorphisms. For Asian populations, all models showed significantly increased risk of ischemic stroke for the G894T (dominant model: OR = 1.58; 95% CI, 1.30-1.91; P = 0.000) and 4b/a polymorphisms (dominant model: OR = 1.46; 95% CI, 1.25-1.71; P = 0.000), even after Bonferroni correction (because 0.000 < 0.017). In white populations, the aa genotype seemed to be protective for ischemic stroke, as indicated by the recessive model (OR = 0.44; 95% CI, 0.22-0.87; P = 0.019). In Asian populations, the T786C polymorphism was significantly associated with ischemic stroke, as found using the dominant (OR = 1.17; 95% CI, 1.02-1.34; P = 0.025) and additive models (OR = 1.18; 95% CI, 1.05-1.33; P = 0.006). CONCLUSIONS: Our comprehensive meta-analysis ascertains that the G894T, 4b/a, and T786C polymorphisms are associated with ischemic stroke risk in Asians. A possible contrasting role of the 4b/a polymorphism in ischemic stroke was indicated in white populations.

Prevalence and extent of right-to-left shunt in migraine: a survey of 217 Chinese patients.

BACKGROUND: Recently, contrast-enhanced transcranial Doppler (cTCD) studies have shown that right-to-left shunt (RLS) may be a risk factor for migraine in Westerners; however, limited data in the literature describes the prevalence of RLS in Chinese patients with migraine. OBJECTIVE: To assess the prevalence of RLS in patients with migraine in China and to evaluate the relationship between the extent of RLS and migraine. METHODS: A total of 217 consecutive patients with a diagnosis of migraine and 100 volunteers were recruited. cTCD was used to assess the prevalence and the extent of RLS in all subjects. RESULTS: In the migraine group, the rate of positive RLS was 44.2% (96/217), with 23.5% (51/217) of these being large. In the healthy group, 28.0% (28/100) were positive for RLS overall, and 5.0% (5/100) were large (P = 0.006; P < 0.001). In patients having migraines with aura (MwA), 66.1% (39/59) were positive for RLS overall, and 37.3% (22/59) were large, which was significantly higher when compared with the healthy group (P < 0.001; P < 0.001); in patients having migraines without aura (MwoA), 36.1% (57/158) were positive for RLS overall, and 18.4% (29/158) were large, which was against significantly higher (P < 0.001; P = 0.003). In the MwoA group, the large RLS rate was also higher than in the healthy group (P = 0.002). CONCLUSIONS: A close correlation has been documented between RLS and migraine, especially MwA, but these relationships exist only when the shunts were large.

Dynamic observation on thyroid function in severe head injury.

The dynamic changes of thyroid hormone levels in patients with severe head injury were observed. The results showed that the serum thyroid hormone levels changed rapidly within several hours after the injury and the mean levels of serum total T3 and T4 (TT3, TT4) decreased while high reverse triiodothyronine (rT3) increased significantly. Serum TT3, TT4 and rT3 levels returned to normal gradually in 2 to 3 weeks after the injury in the surviving group, whereas serum total T4 gradually declined and rT3 steadily increased in the fatal group. The mean levels of serum TSH remained unchanged in both groups. Therefore, the use of the levels of serum thyroid hormones as adjuvant indices can be helpful in making pertinent judgements of the severity and prognosis of severe head injuries.