[OCT analysis of in-stent neointima over 5 years post-DES implantation].

Objective: To investigate the characteristics of neointimal hyperplasia (NIH) in patients with in-stent restenosis (ISR) over 5 years post-drug-eluting stent (DES) implantation based on optical coherence tomography (OCT). Methods: In this cross-sectional study, patients with DES-ISR who underwent OCT examination at PLA General Hospital between March 2010 and March 2022 were retrospectively included. All patients were divided into≤5 years DES-ISR group and>5 years DES-ISR group according to the time interval after DES implantation. Quantitative and qualitative analyses were conducted on OCT images to compare the clinical data and lesion characteristics of two patient groups. Furthermore, the independent clinical predictive factors of in-stent neoatherosclerosis (ISNA) were analyzed by multivariable logistic regression. Results: A total of 230 DES-ISR patients with 249 lesions were included, with an age of (63.1±10.4) years and 188 males (81.7%). The median interval after DES implantation was 6 (2, 9) years. There were 117 patients (122 ISR lesions) in the≤5 years DES-ISR group, and 113 patients (127 ISR lesions) in the>5 years DES-ISR group. Compared with≤5 years DES-ISR,>5 years DES-ISR showed more heterogeneous patterns (65.4% (83/127) vs. 48.4% (59/122), P=0.007), diffuse patterns (46.5% (59/127) vs. 31.2% (38/122), P=0.013), macrophage accumulations (44.1% (56/127) vs. 31.2% (38/122), P=0.035) in NIH and higher prevalence of ISNA (83.5% (106/127) vs. 72.1% (88/122), P=0.031). According to multivariable logistic regression, the independent predictive factor for ISNA was female (OR=0.44, 95%CI 0.21-0.90, P=0.026). Female (OR=0.48, 95%CI 0.23-0.99, P=0.046) and low-density lipoprotein cholesterol level (OR=1.62, 95%CI 1.01-2.59, P=0.046) were independent predictive factors, respectively, for lipid ISNA. Calcified ISNA was independently associated with time interval of post-DES implantation (OR=1.18, 95%CI 1.07-1.29, P=0.001). Conclusion: DES-ISR patients with a time interval of>5 years after stent implantation have a higher prevalence of ISNA and more complex lesions. Gender, the level of low-density lipoprotein cholesterol, and the time interval post-DES implantation are independently correlated with ISNA, lipid ISNA, and calcified ISNA.

[Analysis of the international application of healthy life expectancy].

Healthy life expectancy is based on life expectancy to further identify the healthy component, moving the assessment threshold from the mortality to the whole life cycle, receiving more and more attention worldwide. Nowadays, it has become one of the core indicators of national major strategy and plan. As a comprehensive indicator of health measurement, healthy life expectancy is complicated and multi-dimensional. Different social and cultural backgrounds have different understandings of health and choose different measurement dimensions. Overall, although high-income countries have different choices in their national health plan, healthy life expectancy without activity restriction is by far the most widely used indicator. This paper reviewed the concept and application of healthy life expectancy systematically, drawing on international practical experience to provide reference for the establishment of a healthy life expectancy indicator system in line with the Chinese national conditions.

[Association between digestive tract cancer and severity of coronary artery disease].

Objective: To evaluate the association between digestive tract cancer and anatomical severity of coronary artery disease. Methods: This study enrolled 142 patients with digestive tract cancer who underwent coronary angiography in the Department of Cardiology of the First Medical Center of Chinese PLA General Hospital from 2009 to 2020 as the cancer group. The patients in cancer group were matched with 426 non-cancer patients who underwent coronary angiography at our hospital during the same period in a 1∶3 ratio based on gender and age. All enrolled patients had no previous history of percutaneous coronary intervention or coronary artery bypass grafting surgery. The severity of coronary artery disease was documented and assessed using the SYNTAX score based on angiogram. High SYNTAX score (SXhigh) was defined as SYNTAX score≥22 (upper quartile), while low SYNTAX score (SXlow) was SYNTAX score<22. High NLR (NLRhigh) was NLR≥2.287 (median), while low NLR (NLRlow) was NLR<2.287. The association between digestive tract cancer and severity of coronary artery disease was analyzed using logistic regression analysis. Results: This study included a total of 568 patients, with a mean age of (66.6±8.7) years. Among them, 430 patients (75.7%) were male. The cancer group consisted of 142 patients with digestive tract cancers, with a mean age of (66.5±8.4) years. The non-cancer group consisted of 426 patients, with a mean age of (66.7±8.8) years. The proportion of SXhigh in patients with digestive tract cancers (33.1%, 47 patients) was higher than that in non-cancer patients (23.9%, 102 patients) (P=0.032). Compared to non-cancer patients, SXhigh in patients with digestive tract cancers was higher (OR: 1.614, 95%CI: 1.051-2.481, P=0.029). Subgroup analysis stratified by NLR levels revealed that in the NLRhigh group, patients with digestive tract cancers exhibited a higher severity of coronary artery disease compared to non-cancer patients, with an OR of 1.948 (95%CI: 1.005-3.779, P=0.048). In the NLRlow group, there was no significant relationship between digestive tract cancers and the severity of coronary artery disease, with an OR of 1.277 (95%CI: 0.586-2.781, P=0.538). Conclusions: Digestive tract cancer is associated with the severity of coronary artery disease, and patients with digestive tract cancers have a higher risk of severe coronary artery disease than non-cancer patients. Additionally, there is an association between digestive tract cancers and the severity of coronary artery disease under conditions of high levels of inflammation.

[Protection of side-branch ostium by the jailed balloon technique validated by three-dimensional optical coherence tomography].

Objective: To evaluate the protective effect of jailed balloon technique on side branch (SB) ostium using three-dimensional optical coherence tomography(OCT). Methods: This is a retrospective study. Consecutive coronary disease patients with coronary artery bifurcation lesions who underwent percutaneous coronary intervention (PCI) and completed pre-and post-procedural OCT examinations at the Chinese People's Liberation Army General Hospital from September 2019 to March 2022 were enrolled. Patients were divided into the jailed balloon technique group and the unprotected group according to the options applied for the SB. The SB ostium area difference was calculated from OCT images (SB ostium area difference=post-PCI SB ostium area-pre-PCI SB ostium area). The SB ostium area differences were compared between the two groups and compared further in the subgroup of true bifurcation lesions and non-true bifurcation lesions. In the jailed balloon group, the SB ostium area difference was compared between the active jailed balloon technique and the conventional jailed balloon technique, between the jailed balloon>2.0 mm diameter and the jailed balloon≤2.0 mm diameter, and between the higher balloon pressure (>4 atm, 1 atm=101.325 kPa) and the lower balloon pressure (≤4 atm). Multivariate linear regression analysis was used to explore the correlation between the technical parameters of the jailed balloon technique and the SB protection effect. Results: A total of 176 patients with 236 bifurcation lesions were enrolled, aged (60.7±9.3) years, and there were 128 male patients (72.7%). There were 67 patients in the jailed balloon technique group with 71 bifurcation lesions and 123 patients in the unprotected group with 165 bifurcation lesions. Fourteen patients had 2 to 3 lesions, which were treated in different ways, so they appeared in the unprotected group and the jailed balloon technique group at the same time. The area difference in SB ostium was greater in the jailed balloon group than in the unprotected group (0.07 (-0.43, 1.05)mm2 vs.-0.33 (-0.83, 0.26)mm2, P<0.001), and the results were consistent in the true bifurcation lesion subgroup (0.29 (-0.35, 0.96)mm2 vs.-0.26 (-0.64, 0.29)mm2, P=0.004), while the difference between the two groups in the non-true bifurcation lesion subgroup was not statistically significant (P=0.136). In the jailed balloon technique group, the SB ostium area difference was greater in patients treated with the active jailed balloon technique than in those treated with the conventional jailed balloon technique ((0.43±1.36)mm2 vs. (-0.22±0.52)mm2, P=0.013). The difference in SB ostium area was greater in those using>2.0 mm diameter jailed balloons than in those using≤2.0 mm diameter jailed balloons (0.25 (-0.51, 1.31) mm2 vs.-0.01 (-0.45, 0.63) mm2, P=0.020), while SB ostium area difference was similar between those endowed with higher balloon pressure (>4 atm) compared to those with lower balloon pressure (≤4 atm) (P=0.731). Multivariate linear regression analysis showed that there was a positive correlation between jailed balloon diameter and SB ostium area difference (r=0.344, P=0.019). Conclusions: The jailed balloon technique significantly protects SB ostium, especially in patients with true bifurcation lesions. The active jailed balloon technique and larger diameter balloons may provide more protection to the SB.

[A pretest model of obstructive coronary artery disease based on machine learning: from the C-Strat study].

Objective: To develop a pretest probability model of obstructive coronary artery disease with machine learning based on multi-site Chinese population data. Methods: Chinese regiStry in early deTection and Risk strAtificaTion of coronary plaques (C-Strat) study is a prospective multi-center cohort study, in which consecutive patients with suspected obstructive coronary artery disease and ≥64 detector row coronary computed tomography angioplasty (CCTA) evaluation were included. Data from the patients were randomly split into a training set (70%) and a test set (30%). More than 50% of coronary artery stenosis by CCTA was defined as positive outcome. A boosted ensemble algorithm (XGBoost), 10-fold cross-validation and Bayesian optimization were used to establish a new prediction model-CARDIACS(pretest probability model from Chinese registry in eARly Detection and rIsk stratificAtion of Coronary plaques Study), and a logistic regression was used to establish a model-LOGISTIC in training set. The test set was used for validation and comparison among CARDIACS, LOGISTIC, UDFM (updated Diamond-Forrester Model) and DFCASS(Diamond-Forrester and CASS). Results: The study population included 29 455 patients with age of (57.0±9.7) years and 44.8% women, of whom 19.1% (5 622/29 455) had obstructive coronary artery disease. For CARDIACS, the age, the reason for visit and the body mass index (BMI) were the most important predictive variables. In the independent test set, the area under the curve (AUC) of CARDIACS was 0.72 (95%CI 0.70-0.73), which was significantly superior to that of LOGISTIC (AUC 0.69, 95%CI 0.68-0.71, P=0.015), UDFM (AUC 0.64, 95%CI 0.62-0.65, P<0.001) and DFCASS (AUC 0.66, 95%CI 0.64-0.67, P<0.001), respectively. Conclusion: Based on Chinese population, the study developed a new pretest probability model--CARDIACS, which was superior to the traditional models. CARDIACS is expected to assist in the clinical decision-making for patients with stable chest pain.

[Coronary CT angiography derived fractional flow reserve: opportunity for a win-win cooperation between cardiologists and radiologists].

The advent of coronary CT angiography derived fractional flow reserve (CT-FFR) calculation technology has brought great improvements to the clinical diagnostic process and treatment decision-making towards coronary artery disease. In recent years, CT-FFR technology has gradually begun to be taken into clinical practice in China, however, currently, the popularization is not widespread, and it is imperative to further standardize the clinical application of CT-FFR technology. This paper focused on the opportunities, significance and challenges of CT-FFR application in China from the advantages and disadvantages perspectives of this new technology based on three international studies. Combined with specific national conditions and the latest evidence-based clinical medical results, this paper proposes a win-win cooperation initiative between cardiologists and radiologists for the reference and caution of both clinical practitioners and medical affairs bureaus.

[Some considerations on professional education and teaching reform for public health and preventive medicine].

Following a brief overview of the historical development of undergraduate education of public health and preventive medicine in China's medical universities and colleges, this editorial points out existing issues and dominant challenges, and puts forward compelling demands for undergraduate education in preventive medicine, including in-depth integration with society and population, combined with practice, focusing on problem identificantion and problem solving based on population health, as well as developing undergraduate education programs, education syllabus and courses, construction of teaching materials and off-campus practice teaching bases.

Genome-wide meta-analysis of variant-by-diuretic interactions as modulators of lipid traits in persons of European and African ancestry.

Hypertension (HTN) is a significant risk factor for cardiovascular morbidity and mortality. Metabolic abnormalities, including adverse cholesterol and triglycerides (TG) profiles, are frequent comorbid findings with HTN and contribute to cardiovascular disease. Diuretics, which are used to treat HTN and heart failure, have been associated with worsening of fasting lipid concentrations. Genome-wide meta-analyses with 39,710 European-ancestry (EA) individuals and 9925 African-ancestry (AA) individuals were performed to identify genetic variants that modify the effect of loop or thiazide diuretic use on blood lipid concentrations. Both longitudinal and cross sectional data were used to compute cohort-specific interaction results, which were then combined through meta-analysis in each ancestry. These ancestry-specific results were further combined through trans-ancestry meta-analysis. Analysis of EA data identified two genome-wide significant (p < 5 × 10-8) loci with single nucleotide variant (SNV)-loop diuretic interaction on TG concentrations (including COL11A1). Analysis of AA data identified one genome-wide significant locus adjacent to BMP2 with SNV-loop diuretic interaction on TG concentrations. Trans-ancestry analysis strengthened evidence of association for SNV-loop diuretic interaction at two loci (KIAA1217 and BAALC). There were few significant SNV-thiazide diuretic interaction associations on TG concentrations and for either diuretic on cholesterol concentrations. Several promising loci were identified that may implicate biologic pathways that contribute to adverse metabolic side effects from diuretic therapy.

Alterations in plasma non-esterified fatty acid (NEFA) kinetics and relationship with insulin resistance in polycystic ovary syndrome.

STUDY QUESTION: Are non-esterified fatty acid (NEFA) kinetics altered in women with polycystic ovary syndrome (PCOS)? SUMMARY ANSWER: Women with PCOS, particularly obese subjects, have dysregulated plasma NEFA kinetics in response to changes in plasma insulin and glucose levels, which are associated with insulin resistance (IR) independently of the fasting plasma NEFA levels. WHAT IS KNOWN ALREADY: Elevated plasma NEFA levels are associated with IR in many disorders, although the homeostasis of NEFA kinetics and its relationship to IR in women with PCOS is unknown. STUDY DESIGN, SIZE, DURATION: We prospectively compared insulin sensitivity and NEFA kinetics in 29 PCOS and 29 healthy controls women matched for BMI. PARTICIPANTS/MATERIALS, SETTING, METHODS: This study was conducted in a tertiary institution. Plasma NEFA, glucose and insulin levels were assessed during a modified frequently sampled intravenous glucose tolerance test (mFSIVGTT). Minimal models were used to assess insulin sensitivity (Si) and NEFA kinetics (i.e. model-derived initial plasma NEFA level [NEFA0], phi constant [Φ], reflecting glucose-mediated inhibition of lipolysis and measures of maximum rate of lipolysis [SFFA] and NEFA uptake from plasma [KFFA]). MAIN RESULTS AND THE ROLE OF CHANCE: The study provides new evidence that women with PCOS have defective NEFA kinetics characterized by: (i) lower basal plasma NEFA levels, measured directly and modeled (NEFA0), and (ii) a greater glucose-mediated inhibition of lipolysis in the remote or interstitial space (reflected by a lower affinity constant [Φ]). There were no differences, however, in the maximal rates of adipose tissue lipolysis (SFFA) and the rate at which NEFA leaves the plasma pool (KFFA). The differences observed in NEFA kinetics were exacerbated, and almost exclusively observed, in the obese PCOS subjects. LIMITATIONS, REASONS FOR CAUTION: Our study did not study NEFA subtypes. It was also cross-sectional and based on women affected by PCOS as defined by the 1990 National Institutes of Health (NIH) criteria (i.e. Phenotypes A and B) and identified in the clinical setting. Consequently, extrapolation of the present data to other phenotypes of PCOS should be made with caution. Furthermore, our data is exploratory and therefore requires validation with a larger sample size. WIDER IMPLICATIONS OF THE FINDINGS: Dysfunction in NEFA kinetics may be a marker of metabolic dysfunction in nondiabetic obese women with PCOS and may be more important than simply assessing circulating NEFA levels at a single point in time for understanding the mechanism(s) underlying the IR of PCOS. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by NIH grants R01-DK073632 and R01-HD29364 to R.A.; a Career Development Award from MD Medical Group, Moscow, RF, to D.L. and Augusta University funds to Y.-H.C. RA serves as consultant to Ansh Labs, Medtronics, Spruce Biosciences and Latitude Capital. U.E., Z.A., D.L., R.M., Y.-H.C., R.C.B. and Y.D.I.C. have no competing interests to declare. TRIAL REGISTRATION NUMBER: Not applicable.

Bidirectional Mendelian randomization to explore the causal relationships between body mass index and polycystic ovary syndrome.

STUDY QUESTION: What are the causal relationships between polycystic ovary syndrome (PCOS) and body mass index (BMI)? SUMMARY ANSWER: Bidirectional Mendelian randomization analyses suggest that increased BMI is causal for PCOS while the reverse is not the case. WHAT IS KNOWN ALREADY: The contribution of obesity to the pathogenesis of PCOS is controversial. To date, published genetic studies addressing this question have generated conflicting results and have not utilized the full extent of known single nucleotide polymorphisms associated with body mass index (BMI). STUDY DESIGN, SIZE, DURATION: This cross-sectional Mendelian randomization (MR) and genetic association study was conducted in 750 individuals of European origin and with PCOS and 1567 BMI-matched controls. PARTICIPANTS/MATERIALS, SETTING, METHODS: Cases and controls were matched for BMI as well as for distribution of weight categories (normal weight, overweight, obese). Two-sample MR using inverse variance weighting (IVW) was conducted using a 92-SNP instrument variable for BMI with PCOS as the outcome, followed by two-sample MR with a 16-SNP instrument variable for PCOS with BMI as the outcome. Sensitivity analyses included MR-Egger and maximum likelihood methods. Secondary analyses assessed associations of genetic risk scores and individual SNPs with PCOS, BMI and quantitative androgen-related and glucose homeostasis-related traits. MAIN RESULTS AND THE ROLE OF CHANCE: Each standard deviation genetically higher BMI was associated with a 4.89 (95% CI 1.46-16.32) higher odds of PCOS. Conversely, genetic risk of PCOS did not influence BMI. Sensitivity analyses yielded directionally consistent results. The genetic risk score of 92 BMI SNPs was associated with the diagnosis of PCOS (OR 1.043, 95% CI 1.009-1.078, P = 0.012). Of the 92 BMI risk variants evaluated, none were associated individually with PCOS after considering multiple testing. The association of FTO SNP rs1421085 with BMI was stronger in women with PCOS (ß = 0.071, P = 0.0006) than in controls (ß = 0.046, P = 0.065). LIMITATIONS, REASONS FOR CAUTION: The current sample size, while providing good power for MR and genetic risk score analyses, had limited power to demonstrate association of individual SNPs with PCOS. Cases and controls were not matched for age; however, this was mitigated by adjusting analyses for age. Dietary and lifestyle data, which could have been used to explore the greater association of the FTO SNP with BMI in women with PCOS, was not available. WIDER IMPLICATIONS OF THE FINDINGS: Increasing BMI appears to be causal for PCOS but having PCOS does not appear to affect BMI. This study used the most comprehensive set of SNPs for BMI currently available. Prior studies using fewer SNPs had yielded conflicting results and may have been confounded because cases and controls were not matched for weight categories. The current results highlight the potential utility of weight management in the prevention and treatment of PCOS. STUDY FUNDING/COMPETING INTEREST(S): National Institutes of Health Grants R01-HD29364 and K24-HD01346 (to R.A.), Grant R01-DK79888 (to M.O.G.), Grant U54-HD034449 (to R.S.L.), Grant U19-HL069757 (to R.M.K.). The funders had no influence on the data collection, analyses or conclusions of the study. No conflict of interests to declare. TRIAL REGISTRATION NUMBER: N/A.

[Declaration of Astana and preventive medicine in China].

At the time of the 40th anniversary of the Alma-Ata Declaration, the World Health Organization member states signed the Declaration of Astana. From Health For All to Universal Health Coverage, primary health care is consistantly identified as the key to achieving human health, and preventive services are critical and central component of primary health care. China has provided valuable experience for primary health care to countries around the world. However, with significant socioeconomic changes and rapid population aging, the contexts of primary health care and prevention services in China has undergone tremendous changes. Chronic diseases have become major burden of disease. System development and institution building, health service delivery system development, and the entire society of the country with large population are encountering new and serious challenges. On the basis of reviewing the development of preventive medical services in China for 40 years, Authors analyzes strengths and weaknesses of preventive services in China and looks forward to the challenges and opportunities in the coming decades, from perspective of primary, secondary and tertiary prevention strategies, and proposes suggestions for future development.

Synchronous polypectomy during endoscopic diagnosis of colorectal cancer - is the risk of tumour implantation at the polypectomy site significant?

BACKGROUND: Synchronous polypectomy in colonic malignancies is contentious due to the perceived risks of tumour implantation at polypectomy sites (PS). We assess the risks of tumour implantation after synchronous polypectomy. METHODS: An analysis of all endoscopies for cancer that were accompanied by synchronous polypectomies from 2005 to 2009 was performed. The incidence of metachronous colorectal cancers located at the same segment of a previous PS was the surrogate for tumour implantation. Data on patient demographics, tumour and polyp location(s) and follow-up outcomes were extracted. The rate of metachronous lesions at the same segment of a previous PS between patients who had all synchronous PS resected (Group A) and patients with PS left in-situ (Group B) were compared. RESULTS: Two hundred and eighty-four patients had synchronous polypectomy performed during their initial endoscopy for cancer. Three patients were lost to follow-up and, in the remaining 281 patients, 87 (31.0%) were in Group A while 194 (69%) were in Group B. Median age, gender, tumour location, tumour stage, and pathological characteristics were similar between both groups. 2 (0.7%) patients developed local recurrences. Six (2.1%) patients developed metachronous lesions, four of which were located at the same segment where synchronous polypectomy was previously performed. The rates of metachronous lesions at the PS in groups A and B were similar at 1.1% (1/87) and 1.5% (3/194), respectively (p = 0.795). CONCLUSION: Malignant implantation after synchronous polypectomy in the setting of a newly diagnosed cancer remains unproven. Even if tumor implantation did occur, the incidence is likely low.

Generalization and fine mapping of European ancestry-based central adiposity variants in African ancestry populations.

BACKGROUND/OBJECTIVES: Central adiposity measures such as waist circumference (WC) and waist-to-hip ratio (WHR) are associated with cardiometabolic disorders independently of body mass index (BMI) and are gaining clinically utility. Several studies report genetic variants associated with central adiposity, but most utilize only European ancestry populations. Understanding whether the genetic associations discovered among mainly European descendants are shared with African ancestry populations will help elucidate the biological underpinnings of abdominal fat deposition. SUBJECTS/METHODS: To identify the underlying functional genetic determinants of body fat distribution, we conducted an array-wide association meta-analysis among persons of African ancestry across seven studies/consortia participating in the Population Architecture using Genomics and Epidemiology (PAGE) consortium. We used the Metabochip array, designed for fine-mapping cardiovascular-associated loci, to explore novel array-wide associations with WC and WHR among 15 945 African descendants using all and sex-stratified groups. We further interrogated 17 known WHR regions for African ancestry-specific variants. RESULTS: Of the 17 WHR loci, eight single-nucleotide polymorphisms (SNPs) located in four loci were replicated in the sex-combined or sex-stratified meta-analyses. Two of these eight independently associated with WHR after conditioning on the known variant in European descendants (rs12096179 in TBX15-WARS2 and rs2059092 in ADAMTS9). In the fine-mapping assessment, the putative functional region was reduced across all four loci but to varying degrees (average 40% drop in number of putative SNPs and 20% drop in genomic region). Similar to previous studies, the significant SNPs in the female-stratified analysis were stronger than the significant SNPs from the sex-combined analysis. No novel associations were detected in the array-wide analyses. CONCLUSIONS: Of 17 previously identified loci, four loci replicated in the African ancestry populations of this study. Utilizing different linkage disequilibrium patterns observed between European and African ancestries, we narrowed the suggestive region containing causative variants for all four loci.

Statin-induced expression change of INSIG1 in lymphoblastoid cell lines correlates with plasma triglyceride statin response in a sex-specific manner.

Statins are widely prescribed to lower plasma low-density lipoprotein (LDL) cholesterol levels. They also modestly reduce plasma triglyceride (TG), an independent cardiovascular disease risk factor, in most people. The mechanism and inter-individual variability of TG statin response is poorly understood. We measured statin-induced gene expression changes in lymphoblastoid cell lines derived from 150 participants of a simvastatin clinical trial and identified 23 genes (false discovery rate, FDR=15%) with expression changes correlated with plasma TG response. The correlation of insulin-induced gene 1 (INSIG1) expression changes with TG response (rho=0.32, q=0.11) was driven by men (interaction P=0.0055). rs73161338 was associated with INSIG1 expression changes (P=5.4 × 10-5) and TG response in two statin clinical trials (P=0.0048), predominantly in men. A combined model including INSIG1 expression level and splicing changes accounted for 29.5% of plasma TG statin response variance in men (P=5.6 × 10-6). Our results suggest that INSIG1 variation may contribute to statin-induced changes in plasma TG in a sex-specific manner.

Meta-analysis of genome-wide association studies of HDL cholesterol response to statins.

BACKGROUND: In addition to lowering low density lipoprotein cholesterol (LDL-C), statin therapy also raises high density lipoprotein cholesterol (HDL-C) levels. Inter-individual variation in HDL-C response to statins may be partially explained by genetic variation. METHODS AND RESULTS: We performed a meta-analysis of genome-wide association studies (GWAS) to identify variants with an effect on statin-induced high density lipoprotein cholesterol (HDL-C) changes. The 123 most promising signals with p<1×10-4 from the 16 769 statin-treated participants in the first analysis stage were followed up in an independent group of 10 951 statin-treated individuals, providing a total sample size of 27 720 individuals. The only associations of genome-wide significance (p<5×10-8) were between minor alleles at the CETP locus and greater HDL-C response to statin treatment. CONCLUSIONS: Based on results from this study that included a relatively large sample size, we suggest that CETP may be the only detectable locus with common genetic variants that influence HDL-C response to statins substantially in individuals of European descent. Although CETP is known to be associated with HDL-C, we provide evidence that this pharmacogenetic effect is independent of its association with baseline HDL-C levels.

Meta-analysis of genome-wide association studies in African Americans provides insights into the genetic architecture of type 2 diabetes.

Type 2 diabetes (T2D) is more prevalent in African Americans than in Europeans. However, little is known about the genetic risk in African Americans despite the recent identification of more than 70 T2D loci primarily by genome-wide association studies (GWAS) in individuals of European ancestry. In order to investigate the genetic architecture of T2D in African Americans, the MEta-analysis of type 2 DIabetes in African Americans (MEDIA) Consortium examined 17 GWAS on T2D comprising 8,284 cases and 15,543 controls in African Americans in stage 1 analysis. Single nucleotide polymorphisms (SNPs) association analysis was conducted in each study under the additive model after adjustment for age, sex, study site, and principal components. Meta-analysis of approximately 2.6 million genotyped and imputed SNPs in all studies was conducted using an inverse variance-weighted fixed effect model. Replications were performed to follow up 21 loci in up to 6,061 cases and 5,483 controls in African Americans, and 8,130 cases and 38,987 controls of European ancestry. We identified three known loci (TCF7L2, HMGA2 and KCNQ1) and two novel loci (HLA-B and INS-IGF2) at genome-wide significance (4.15 × 10(-94)

[Value of fragmented QRS wave in evaluating the prognosis of patients with coronary artery disease].

Objective: The aim of the current study was to investigate the predictive value of fragmented QRS wave ( fQRS) for the prognosis of patients with coronary heart disease (CHD). Methods: A total of 714 consecutive patients with confirmed CHD were included from Department of Cardiology, General Hospital of PLA between January 2013 and January 2014, and were divided into fQRS group and non-fQRS group based on the presence of fQRS wave or not according to Electrocardiograph (ECG). The baseline, ECG characteristic value, the echocardiography results of the patients were compared between the two groups. Cardiac events were recorded in all patients during 12 months' follow-up. Subgroup analysis was also conducted among patients with abnormal Q wave to investigate the association between fQRS and cardiovascular events. Results: A total of 673 patients completed the follow-up, with 533 in fQRS group and 140 in non-fQRS group. The P wave duration in the fQRS group was longer than non-fQRS group [(92±21) vs (82±23)ms, P<0.01]. The left ventricular ejection fraction (LVEF) value in the fQRS group was lower than non-fQRS group (42%±22% vs 49%±15%, P<0.01) according to echocardiography results. The subgroup analysis with abnormal Q wave showed that compared with non-fQRS group, the left ventricular ejection fraction (LVEF) value in the group of fQRS was lower (38%±21% vs 50%±7%, P<0.01). There was statistically significant in the mortality of patients within follow-up period between the two groups (P<0.05), and the survival time in fQRS group was shorter than the non-fQRS group [(28.3±3.4) vs (30.5±1.5)months, P<0.01]. Conclusion: FQRS presence in body surface ECG of CHD patients with abnormal Q wave is a sign for increased risk of cardiovascular events, which can serve as an indicator to identify CHD patients at high risk of death.

[A pilot study on the noninvasive fluid hemodynamic investigation of coronary plaque].

Objective: To characterize the hemodynamic force towards coronary plaque based on noninvasive coronary computed tomographic angiography and to investigate its relationship with plaque features and stenosis severity by computational fluid dynamics. Methods: Twenty-six patients underwent invasive fractional flow reserve measurement following coronary computed tomography angiography examination from March to September 2016 were retrospectively included. Computational fluid dynamics was applied and wall shear stress (WSS) and axial plaque stress (APS), which extracted the axial component of hemodynamic stress acting on stenotic lesions, were calculated based on the results of noninvasive coronary computed tomographic angiography. Plaque analysis was performed to elucidate plaque features and relative plaque burden. The fluid dynamics distributions in lesions with different stenosis severity were investigated. Results: Thirty-one coronary plaques with satisfactory imaging quality were analyzed, there were 11 (35.5%) dominant low WSS (<1 Pa) lesion and 20 high WSS lesion (64.5%), 8(25.8%) net retrograde APS lesion and 23(74.2%) anterograde lesion. Plaque volume was (78.5±48.6) mm(3) and plaque burden was (69.1±12.1)% in the low WSS group, which was(60.5±57.3) mm(3), and(57.5±14.0)%, respectively in the high WSS group, the plaque burden was significantly higher in the low WSS group than in the high WSS group (P=0.028), while the percentage of calcified plaque, fibrotic plaque and lipid core volume were similar between the two groups (P>0.05). Plaque volume was (79.7±69.1) mm(3) and plaque burden was(68.7±13.7)% in the group with anterograde-dominant APS plaque, which was(61.7±24.9)mm(3), and(68.9±10.4)%, respectively in the net retrograde APS lesion group (P>0.05). Percentage of lipid core area was significantly higher in the anterograde lesion group than in the retrograde lesion group ((25.1±18.1)% vs.(10.8±12.7)%, P=0.049). Both WSS and APS were significant higher in the severe obstructive coronary stenosis group than in non-severe obstructive coronary stenosis group (P<0.05). Although there was no difference in WSS between functional coronary ischemia group and non-functional coronary ischemia group ( (13.3±8.7) Pa vs. (12.5±14.2) Pa, P>0.05), the distribution of APS was different between the functional coronary ischemia group and non-functional coronary ischemia group ((1 698.8±652.6) Pa vs. (981.4±787.5) Pa, P<0.05). Conclusion: WSS and APS can uniquely characterize the stenotic segment and has a strong relationship with lesion geometry. APS may be related to the necrotic core plaque and functional coronary ischemia. Clinical application of these hemodynamic and geometric indices may be helpful to assess the future risk of plaque progress and plaque rupture, which will be helpful on determining respective treatment strategy for patients with coronary artery disease.

Immunogenicity and antigenicity of a recombinant chimeric protein containing epitopes of poliovirus type 1.

To design a vaccine that simultaneously prevents both rotavirus (RV) and poliovirus (PV), a PV type 1 (PV1) chimeric protein using RV VP6 as a vector (VP6F) was constructed, expressed in Escherichia coli expression system and characterized by SDS-PAGE, Western blot, immunofluorescence assay and neutralization test. The results showed that the chimeric protein reacted with anti-VP6F and anti-PV1 antibodies and elicited production of serum antibodies against the chimeric protein in guinea pigs. Antibodies against the chimeric protein neutralized RV Wa and PV1 infection in vitro. The results provided a relevant possibility of developing novel approaches in the rational design of vaccines effective against both RV and PV.