MR Uniformity Ratio Estimates to Evaluate Ventricular Mechanical Dyssynchrony and Prognosis After ST-Segment Elevation Myocardial Infarction.

BACKGROUND: The impact of left ventricular mechanical dyssynchrony (LVMD) on the long-term prognosis of ST-segment elevation myocardial infarction (STEMI) is unclear. HYPOTHESIS: MR uniformity ratio estimates (URE) can detect LVMD and assess STEMI prognosis. STUDY TYPE: Retrospective analysis of a prospective multicenter registry (EARLY-MYO trial, NCT03768453). POPULATION: Overall, 450 patients (50 females) with first-time STEMI were analyzed, as well as 40 participants without cardiovascular disease as controls. FIELD STRENGTH/SEQUENCE: 3.0-T, balanced steady-state free precession cine and late gadolinium enhancement imaging. ASSESSMENT: MRI data were acquired within 1 week of symptom onset. Major adverse cardiovascular events (MACEs), including cardiovascular death, nonfatal re-infarction, hospitalization for heart failure, and stroke, were the primary clinical outcomes. LVMD was represented by circumferential URE (CURE) and radial URE (RURE) calculated using strain measurements. The patients were grouped according to clinical outcomes or URE values. Patients' clinical characteristics and MR indicators were compared. STATISTICAL TESTS: The Student's t-test, Mann-Whitney U test, chi-square test, Fisher's exact test, receiver operating characteristic curve analysis with area under the curve, Kaplan-Meier analysis, Cox regression, logistic regression, intraclass correlation coefficient, c-index, and integrated discrimination improvement were used. P < 0.05 was considered statistically significant. RESULTS: CURE and RURE were significantly lower in patients with STEMI than in controls. The median follow-up was 60.5 months. Patients with both lower CURE and RURE values experienced a significantly higher incidence of MACEs by 3.525-fold. Both CURE and RURE were independent risk factors for MACEs. The addition of UREs improved diagnostic efficacy and risk stratification based on infarct size and left ventricular ejection fraction (LVEF). The indicators associated with LVMD included male sex, serum biomarkers (peak creatine phosphokinase and cardiac troponin I), infarct size, and LVEF. DATA CONCLUSION: CURE and RURE may be useful to evaluate long-term prognosis after STEMI. EVIDENCE LEVEL: 4 TECHNICAL EFFICACY: Stage 2.

Joint association of physical activity and diet quality with dyslipidemia: a cross-sectional study in Western China.

OBJECTIVE: This study aims to investigate the prevalence of dyslipidemia and assess the joint association of physical activity (PA) and diet quality on dyslipidemia risk in urban areas of Xinjiang. METHODS: Conducted from July 2019 to September 2021 in Xinjiang, China, this cross-sectional study involved 11,855 participants (mean age 47.1 ± 9.4 years, 53.1% male). Standard methods were used to measure plasma cholesterol levels, and validated questionnaires were employed to evaluate dietary habits and PA. The definition of dyslipidemia is based on 2023 Chinese guidelines for lipid management. PA was divided into guideline-recommended moderate-to-vigorous physical activity (MVPA) and non-MVPA, following World Health Organization guidelines. The Food Frequency Questionnaire was used to obtain the intake frequency of each dietary term. Each item was scored based on consumption frequency and divided into three groups (good, intermediate, and poor) based on total dietary score. Multivariate logistic regression analysis was performed to identify dyslipidemia risk factors, as well as the joint association of PA and diet quality. RESULTS: Dyslipidemia prevalence among urban adults in Xinjiang was 39.3%, with notable sex disparities (52.6% in males vs. 24.3% in females, P < 0.001). Among participants with dyslipidemia, the awareness, treatment and control rates were 6.9%, 3.1%, and 1.9%, respectively. A significant multiplicative interaction between PA and diet quality is associated with dyslipidemia (P for interaction < 0.05). Less PA and poor diet quality were associated with an increased odds of dyslipidemia. Even individuals with poor (OR = 1.464, 95% CI: 1.106-1.939) or intermediate (OR = 1.229, 95% CI: 1.003-1.505) diet quality but adhering to recommended MVPA had lower odds of dyslipidemia compared to those with good diet quality but inadequate MVPA (OR = 1.510, 95% CI: 1.252-1.821). CONCLUSIONS: Dyslipidemia prevalence was 39.3% in urban adults in Xinjiang, with limited awareness, treatment, and control. Following guideline-recommended MVPA and maintaining good diet quality were protective against dyslipidemia. Low levels of PA associated with a higher prevalence of dyslipidemia, even in individuals with good diet quality.

Prognostic value of fibrinogen-to-albumin ratio combined with coronary calcification score in patients with suspected coronary artery disease.

OBJECTIVE: The aim of this work was to evaluate the predictive value of FAR combined with CACS for MACCEs. BACKGROUND: The fibrinogen-albumin-ratio (FAR), a novel biomarker of inflammation, is associated with the severity of coronary artery disease (CAD). Coronary calcification score (CACS) is associated with the severity of coronary stenosis and is closely related to the prognosis of CAD patients. What is the prognostic value of FAR in patients with chest pain, which has not been reported. This study aims to evaluate the relationship between CACS and FAR and their impact on prognosis in patients with suspected CAD. METHODS: We used information from 12,904 individuals who had coronary computed tomography angiography (CTA) for chest pain and tracked down any significant adverse cardiac and cerebrovascular events (MACCEs). The following formula was used to calculate FAR: fibrinogen (g/L)/albumin (g/L). Patients were separated into groups with greater levels of FAR (FAR-H) and lower levels of FAR (FAR-L) in accordance with the ideal cut-off value of FAR for MACCEs prediction. In addition, patients were divided into three groups based on their CACS scores (CACS ≤ 100, 100 < CACS ≤ 400, and CACS > 400). RESULTS: 4946 patients [62(55-71) years, 64.4% male] were ultimately enrolled in the present study. During follow-up, a total of 234 cases (4.7%) of MACCEs were documented. Linear regression analysis results showed that CACS (R2 = 0.004, Standard ß = 0.066, P < 0.001) was positively associated with FAR in patients with chest pain.Compared to ones with FAR-L, FAR-H had an increased risk for MACCEs (adjusted HR 1.371(1.053-1.786) P = 0.019). Multivariate Cox regression showed that age (adjusted HR 1.015 95% CI 1.001-1.028;p = 0.03), FAR (adjusted HR 1.355 95% CI 1.042-1.763;p = 0.023),FBG (adjusted HR 1.043 95% CI 1.006-1.083;p = 0.024) and CACS (adjusted HR 1.470 95% CI 1.250-1.727;p < 0.001) were the independent risk factors for MACCEs. The FAR and CACS significantly improved MACCEs risk stratification, contributing to substantial net reclassification improvement ( NRI 0.122, 95% CI 0.054-0.198, P < 0.001) and integrated discrimination improvement(IDI 0.011, 95% CI 0.006-0.017, P < 0.001). CONCLUSION: FAR was an independent risk factor for MACCEs. The results showed that CACS was positively associated with FAR in patients with suspected CAD. A higher level of FAR and heavier coronary calcification burden was associated with worse outcomes among patients with suspected CAD. FAR and CACS improved the risk identification of patients with suspected CAD, leading to a significant reclassification of MACCEs.

AT1R gene rs389566 polymorphism contributes to MACCEs in hypertension patients.

OBJECTIVE: To investigate the possible association between AT1R gene polymorphisms and major adverse cardiovascular and cerebrovascular events (MACCEs) in hypertension patients combined with or without coronary artery disease (CAD) in Xinjiang. METHODS: 374 CAD patients and 341 non-CAD individuals were enrolled as study participants and all of them have a hypertension diagnosis. AT1R gene polymorphisms were genotyped by SNPscan™ typing assays. During the follow-up in the clinic or by telephone interview, MACCEs were recorded. Kaplan-Meier curves and Cox survival analyses were used to explore the association between AT1R gene polymorphisms and the occurrence of MACCEs. RESULTS: AT1R gene rs389566 was associated with MACCEs. The TT genotype of the AT1R gene rs389566 had a significantly higher probability of MACCEs than the AA + AT genotype (75.2% vs. 24.8%, P = 0.033). Older age (OR = 1.028, 95% CI: 1.009-1.0047, P = 0.003) and TT genotype of rs389566 (OR = 1.770, 95% CI: 1.148-2.729, P = 0.01) were risk factors of MACCEs. AT1R gene rs389566 TT genotype may be a predisposing factor for the occurrence of MACCEs in hypertensive patients. CONCLUSION: We should also pay more attention to the prevent of MACCEs in hypertension patients combined with CAD. Especially those elderly hypertensive patients carrying AT1R rs389566 TT genotype requires avoidance of unhealthy lifestyle, better management of blood pressure control and reduce the occurrence of MACCEs.

Peak early diastolic strain rate improves prediction of adverse cardiovascular outcomes in patients with ST-elevation myocardial infarction.

BACKGROUND: The prognostic role of diastolic dysfunction measured by the circumferential peak early diastolic strain rate (PEDSR) on ST-elevation myocardial infarction (STEMI) is not completely established. OBJECTIVES: We aimed to investigate the prognostic value of diastolic function by measuring PEDSR within 1 week after STEMI. METHODS: The cardiac magnetic resonance (CMR) pictures of 420 subjects from a clinical registry study (NCT03768453) were analyzed and the composite major adverse cardiac events (MACEs) were followed up. RESULTS: The PEDSR of patients was significantly lower compared with that of control subjects (P < 0.001). Within the median follow-up period of 52 months, PEDSR of patients who experienced MACEs deceased more significantly than that of patients without MACEs (P < 0.001). After adjusting with clinical or CMR indexes, per 0.1/s reduction of PEDSR increased the risks of MACEs to 1.402 or 1.376 fold and the risk of left ventricular (LV) remodeling to 1.503 or 1.369 fold. When PEDSR divided by best cutoff point, significantly higher risk of MACEs (P < 0.001) and more remarkable LV remodeling (P < 0.001) occurred in patients with PEDSR ≤ 0.485/s. Moreover, when adding the PEDSR to the conventional prognostic factors such as LV ejection fraction and infarction size, better prognostic risk classification models were created. Finally, aging, tobacco use, remarkable LV remodeling, and a low LV ejection fraction were factors related with the reduction of PEDSR. CONCLUSIONS: Diastolic dysfunction has an important prognostic effect on patients with STEMI. Measurement of the PEDSR in the acute phase could serve as an effective index to predict the long-term risk of MACEs and cardiac remodeling.

Association of NFKB1 gene rs28362491 mutation with the occurrence of major adverse cardiovascular events.

BACKGROUND: Several studies have reported that NFKB1 gene rs28362491 polymorphism was associated with susceptibility to coronary heart disease in populations of different genetic backgrounds. To date, there have been no studies on the association between NFKB1 gene rs28362491 polymorphism and the occurrence of major adverse cardiac and cerebrovascular event (MACCE). The present study was to explore the relationship between NFKB1 gene rs28362491 polymorphism and MACCEs to investigate whether identifying NFKB1 gene polymorphism is beneficial to evaluating MACCE risks and patients' prognoses. METHODS: We recruited 257 high-risk of cardiovascular disease patients with chest pain or precordial discomfort. The SNPscan™ were used to analyze the NFKB1 gene rs28362491 polymorphism. All patients were followed up in the clinic or by telephone interview for MACCEs. RESULTS: During the followed-up time (mean: 30.1 months) 49 patients had MACCEs (19.1%). Patients with the different genotypes of NFKB1 rs28362491 had different incidence rate of MACCE. The incidence of MACCE in patients carried II, ID and DD genotype was 16.5%, 15.9%, 32.6%, respectively. Log-rank analysis showed that the survival rate in patients with NFKB1 rs28362491 DD genotype was much lower than that in II or ID genotype carriers (P = 0.034). After excluding the influence of traditional risk factors of MACCEs, Cox regression showed that the DD genotype carriers had 2.294-fold relative risk of MACCEs comparing with patients carried II or ID genotype. CONCLUSION: The NFKB1 gene rs28362491 mutant was an independent predictor of worse long-term prognosis for MACCEs. Therefore, identifying NFKB1 gene rs28362491 mutant may be used as a good way for guiding the standardized management of patients with high-risk of cardiovascular diseases.

GLUT4 gene rs5418 polymorphism is associated with increased coronary heart disease risk in a Uygur Chinese population.

BACKGROUND: To explore possible associations between glucose transporter 4 (GLUT4) genetic polymorphisms in the patients with coronary heart disease (CHD) in Han and Uygur Chinese populations in Xinjiang, China. METHODS: Two GLUT4 polymorphisms (rs5418 and rs5435) were genotyped in 1262 Han (628 CHD patients and 634 healthy controls) and 896 Uyghur (397 CHD patients and 499 healthy controls) Chinese populations. RESULTS: In the Han Chinese population, there were no significant differences in allelic or genotypic distribution of rs5418 and rs5435 between the CHD and control groups (all P > 0.05). However, in the Uygur population, there were significant differences in genotype and allele distributions for rs5418 between CHD and the control group (all P < 0.05). Binary Logistic regression analysis showed that carriers with the rs5418 A allele had a higher risk of CHD compared to carriers of the rs5418 G allele (OR = 1.33, 95% CI: 1.069-1.649, P = 0.01), after adjustment for gender, age, drinking and smoking behavior, hypertension and diabetes. Furthermore, haploid association analysis of the two SNP loci of the GLUT4 gene showed that the AC haplotype was associated with CHD in the Uygur population (P = 0.001598; OR = 1.36, 95% CI = 1.1228-1.6406). CONCLUSIONS: rs5418 GLUT4 gene variants are associated with CHD in the Uygur Chinese population.

Long noncoding RNA MALAT1 polymorphism predicts MACCEs in patients with myocardial infarction.

BACKGROUND: Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) participates in the occurrence and development of cardiovascular and cerebrovascular diseases such as stroke and coronary heart disease by regulating inflammatory reactions, programmed cell death, and other pathological processes. Previous studies revealed that the MALAT1 gene polymorphism was associated with cardiac and cerebrovascular diseases. However, the prognostic role of the MALAT1 polymorphism in major adverse cardiac and cerebrovascular events (MACCEs) remains unknown. Therefore, this study intends to explore the association between the MALAT1 rs3200401 polymorphism and MACCEs. METHOD: We enrolled 617 myocardial infarction (MI) patients and 1125 control participants who attended the First Affiliated Hospital of Xinjiang Medical University from January 2010 to 2018. SNPscan™ typing assays were used to detect the MALAT1 rs3200401 genotype. During the follow-up, MACCEs were recorded. Kaplan-Meier curves and univariate and multivariate Cox survival analyses were used to explore the correlation between MALAT1 gene polymorphisms and the occurrence of MACCEs. RESULTS: Among the total participants and MI patients, the frequencies of the T allele (total Participants 19.5% vs. 15.3%, P = 0.047, MI patients 20.7% vs. 14.1%, P = 0.014) and CT + TT genotypes (total Participants 37.4% vs. 28.1%, P = 0.013, MI patients 39.5% vs. 25.8%, P = 0.003) were significantly higher in subjects with MACCEs than in subjects without MACCEs. However, in control participants, the frequencies of the T allele (16.6% vs. 16.0%, P = 0.860) and CT + TT genotypes (31.4% vs. 29.3%, P = 0.760) were not higher in subjects with MACCEs than in subjects without MACCEs. In addition, among the total participants and MI patients, the Kaplan-Meier curve analysis indicated that the subjects with rs3200401 CT + TT genotypes had a higher incidence of MACCEs than CC genotype carriers (P = 0.015, P = 0.001). Nevertheless, similar results were not observed in the control participants (P = 0.790). Multivariate Cox regression indicated that compared with patients with the CC genotype, patients with CT + TT genotypes had a 1.554-fold increase in MACCE risk (hazard ratio: 1.554, 95% confidence interval: 1.060-2.277, P = 0.024). CONCLUSIONS: The MALAT1 rs3200401 CT + TT genotypes could be a risk factor for MACCEs in MI patients, suggesting that the MALAT1 gene may become a biomarker for poor prognosis in MI patients.

Association between CCN1 gene polymorphism and acute coronary syndrome in Chinese Han and Uygur populations.

BACKGROUND: CCN1 plays a crucial role in the modulation of cardiovascular diseases. However, whether CCN1 genetic variants are involved in the susceptibility of ACS remains unknown. Hence, the present study investigates the association between CCN1 polymorphisms and ACS among Han and Uygur populations in Xinjiang, China. RESULTS: In this case-control study, 1234 Han (547 ACS patients and 687 controls) and 932 Uygur (471 ACS patients and 461 controls) were genotyped using SNPscanTM for three single-nucleotide polymorphisms (SNPs, rs6576776, rs954353, and rs3753794) of the human CCN1 gene. In the Uygur population, we found that the detected frequencies of the C allele (25.3% vs. 18.3%, P<0.001) and CC genotype (6.4% vs. 3.0%, P=0.001) of rs6576776 were significantly higher in the ACS patients than in the control participants. Differences in rs6576776 regarding the dominant model (CC+CG vs. GG, 44.2% vs. 55.8%, P=0.001) and the recessive model (CC vs. CG+GG, 6.4% vs. 93.6%, P=0.016) were observed between the two groups. The frequencies of the GGC and AGC haplotypes in those with ACS were significantly higher than those in the control group (all P<0.05) in the Uygur population. After adjusting for hypertension, diabetes, lipids and smoking, all of which indicate that the rs6576776 C allele is associated with higher risk of ACS (odds ratio (OR)=1.798, 95% confidence interval (CI), 1.218-2.656, P=0.003). In Han population, neither the distribution of genotypes and alleles of the CCN1 gene three SNPs nor the distribution of haplotypes constructed with the three SNPs exhibited a significant difference between the ACS patients and control participants. CONCLUSIONS: Our study document that the CCN1 gene rs6576776 C allele is associated with higher susceptibility of ACS and that the frequencies of GGC and AGC haplotypes are higher among the Uygur ACS patients.

Genetic polymorphism of IDOL gene was associated with the susceptibility of coronary artery disease in Han population in Xinjiang, China.

BACKGROUND: Coronary artery disease (CAD) is the leading cause of death worldwide. In this study, we aimed to explore whether some genetic variants of the human IDOL gene were associated with CAD among Chinese population in Xinjiang. METHODS: We designed two independent case-control studies. The first one included in the Han population (448 CAD patients and 343 controls), and the second one is the Uygur population (304 CAD patients and 318 controls). We genotyped three SNPs (rs2072783, rs2205796, and rs909562) of the IDOL gene. RESULTS: Our results revealed that, in the Han female subjects, for rs2205796, the distribution of alleles, dominant model (TT vs. GG + GT) and the additive model (GG + TT vs. GT) showed significant differences between CAD patients and the control subjects (P = 0.048, P = 0.014, and P = 0.032, respectively). CONCLUSIONS: The rs2205796 polymorphism of the IDOL gene is associated with CAD in the Chinese Han female population in Xinjiang, China.

FBXW7 gene polymorphism is associated with type 2 diabetes in the Uygur population in Xinjiang, China.

BACKGROUND: FBXW7 gene expression is positively correlated with glycolipid metabolism and is associated with diabetes in animal models. In the current study, we focused on exploring whether genetic variants of the FBXW7 gene were associated with type 2 diabetes (T2DM) and the risk factors for T2DM in Uygur people in Xinjiang, China. METHODS: A total of 2164 Chinese Uygur subjects (673 T2DM patients and 1491 controls) were recruited for our case-control study, and four SNPs (rs10033601, rs2255137, rs2292743 and rs35311955) of the FBXW7 gene were genotyped using the improved multiplex ligation detection reaction (iMLDR) technique. RESULTS: Our study showed that the genotypes using the overdominant model (GA vs AA + GG) of rs10033601 and using the overdominant model (TA vs TT + AA) of rs2292743 were significantly different between T2DM patients and the controls (P = 0.005 and P = 0.012, respectively). After multivariate adjustments for confounders, the rs10033601 and rs2292743 SNPs were still independent risk factors for T2DM [GA vs AA + GG: odds ratio = 1.35, 95% confidence interval (CI) = 1.12-1.64, P = 0.002; TA vs TT + AA: OR = 1.28, 95% CI = 1.06-1.55, P = 0.011]. Participants within the Chinese Uygur populations and who with the GA genotype of rs10033601 and the TA genotype of rs2292743 were associated with significantly elevated glucose levels. CONCLUSIONS: Our study revealed that both rs10033601 and rs2292743 of the FBXW7 gene were associated with T2DM in the Uygur populations in Xinjiang.

Auditory evoked potential in stranded melon-headed whales (Peponocephala electra): With severe hearing loss and possibly caused by anthropogenic noise pollution.

Highly concentrated live mass stranding events of dolphins and whales happened in the eastern coast of China between June and October 2021. The current study adopted the non-invasive auditory evoked-potential technique to investigate the hearing threshold of a stranded melon headed whale (Peponocephala electra) at a frequency range of between 9.5 and 181 kHz. It was found that, at the frequency range of from 10 to 100 kHz, hearing thresholds for the animal were between 20 and 65 dB higher than those of its phylogenetically closest species (Pygmy killer whale). The severe hearing loss in the melon headed whale was probably caused by transient intense anthropogenic sonar or chronic shipping noise exposures. The hearing loss could have been the cause for the observed temporal and spatial clustered stranding events. Therefore, there is need for noise mitigation strategies to reduce noise exposure levels for marine mammals in the coastal areas of China.

Riverside underwater noise pollution threaten porpoises and fish along the middle and lower reaches of the Yangtze River, China.

The Yangtze River exhibits a high biodiversity and plays an important role in global biodiversity conservation. As the world's busiest inland river in regard to shipping, little attention has been paid to underwater noise pollution. In 2017, the underwater noise level in 25 riverside locations along the middle and lower reaches of the Yangtze River mainly at night time were investigated by using passive acoustic monitoring method. Approximately 88% and 40% of the sampled sites exhibit noise levels exceeding the underwater acoustic thresholds of causing responsiveness and temporary threshold shift, respectively, in cetacean. Noise pollution may impose a high impact on fish with physostomous swim bladders and Weberian ossicles, such as silver carp, bighead carp, goldfish and common carp, whereas it may affect fish with physoclistous swim bladders and without Weberian ossicles, such as lake sturgeon and paddlefish, to a lesser extent. Noise levels reductions of approximately 10 and 20 dB were observed in the middle and lower reaches, respectively, of the Yangtze River over the 2012 level. The green development mode of the ongoing construction of green shipping in the Yangtze River Economic Belt, including the development of green shipping lanes, ports, ships and transportation organizations, may account for the alleviated underwater noise pollution. Follow-up noise mitigation endeavors, such as the extension of ship speed restrictions and the study and implementation of the optimal navigation speed in ecologically important areas, are required to further reduce the noise level in the Yangtze River to protect local porpoises and fish.

[Establishment of a New-generation High-throughput Proteomic Profiling of Transcription Factor in Human Atrial Tissue].

OBJECTIVE: To explore for the establishment of an experimental technique for profiling transcription factors, namely transcription factor response elements (TFRE), with high throughput and efficiency using human atrial tissue. METHODS: Postoperative right atrial tissues from 2 patients, one with preoperative atrial fibrillation and the one with no preoperative atrial fibrillation, were included in the study. The nucleus protein was extracted from the human atrial tissue, and the protein concentration was then measured. A solution with a complex formed through combining magnetic beads with concatenated tandem array of the consensus transcription factor response element DNA sequence (beads-catTFRE) was prepared, and the beads-catTFREs were then used to enrich transcription factors in the nucleoprotein extraction. SDS-PAGE electrophoresis was performed after dissociating beads-catTFRE from nucleoprotein with high temperature and high salt. The gel was then cut and faded before enzymolysis by trypsin in the gels was performed. Acetonitrile was used to extract the peptides from the gels, and the peptide solution was then dried. After that, we dissolved the peptides and performed mass spectrum tests, and the data were analyzed and processed with Firmiana one-stop proteomic analysis platform. RESULTS: In this study, 220 and 181 transcription factors were identified in the normal right atrial tissue and the right atrial tissue with atrial fibrillation, respectively. A total of 241 transcription factors were identified in the two groups. Among the 241 transcription factors, 12 were in the top 10% of those transcription factors that were above the median expression level of the normal right atrial tissue, and 12 transcription factors were in the top 10% of those above the median expression level of the right atrial tissue with atrial fibrillation. CONCLUSION: The high-throughput profiling method established in this study has high coverage, and the data collected can be used to support further validation studies.

[The Effect of CYP4 F2 Polymorphism on Initial Warfarin Dose in Patients with Heart Valve Replacement].

OBJECTIVE: To study the effect of cytochrome P-4504F2 ( CYP4 F2) gene polymorphism on the initial dose of warfarin in patients after mechanical heart valve replacement. METHODS: We collected 350 patients receiving warfarin after mechanical heart valve replacement from January 2013 to December 2015 in our hospital. According to the international standardized ratio (INR) ≥2 at the initial stage after surgery, the patients were divided into two groups: INR≥2 group and INR<2 group. We selected the blood samples of all the 350 patients with testing the CYP4 F2 gene type of each patient, and analyzed the effect of CYP4 F2 gene polymorphism on the initial dose of warfarin after mechanical heart valve replacement (the average daily dose during hospitalization of patients 5-10 days after mechanical heart valve replacement). RESULTS: There was no statistical significance in the initial dose of warfarin among patients with different CYP4 F2 genotypes. However, warfarin dose was higher in CYP4 F2 TT genotype than in CYP4 F2 CC carriers ((3.37±0.68) mg vs. (2.94±0.74) mg, P<0.05) in INR≥2 group; In patients with the same genotype, the initial dose of warfarin in the CYP4 F2 CC ((4.02±0.58) mg vs. (2.94±0.74) mg) and CYP4 F2 CT genotypes ((4.15±0.88) mg vs. (3.18±0.82) mg) of INR<2 group was higher than that in INR≥2 group ( P<0.05). Gender, age, body mass index (BMI), comorbidities (hypertension, diabetes mellitus, coronary heart disease, atrial fibrillation), cytopigment P-450 2C9 ( CYP2 C9), CYP4 F2 and vitamin K peroxide-reductase complex 1 ( VKORC1) gene polymorphism and INR compliance were included in multiple linear regression analysis. The regression equation was as follows: warfarin initial dose (mg) =-8.634+0.352×BMI (kg/m 2) +1.102× CYP4 F2 genotype (CC or CT values 1, TT values 2) +2.147× VKORC1 (AA or AG values 1, GG values 2) +1.325×INR ( INR≥2 values 0, INR<2 values 1). The coefficient of determination ( R 2) of regression equation was 0.431 ( P<0.05). CONCLUSION: CYP4 F2 gene polymorphism may affect the initial dose of warfarin in patients after heart valve replacement, and this effect is also affected by body characteristics and other factors.

rAAV9-Mediated MEK1 Gene Expression Restores Post-conditioning Protection Against Ischemia Injury in Hypertrophic Myocardium.

PURPOSE: We investigated whether increased expression of activated mitogen-activated protein kinase (MAPK) kinases 1 (MEK1) restores ischemic post-conditioning (IPostC) protection in hypertrophic myocardium following ischemia/reperfusion (I/R) injury. METHODS: C57Bl/6 mice received recombinant adeno-associated virus type 9 (rAAV9)-mediated activated MEK1 gene delivery systemically, then following the induction of cardiac hypertrophy via transverse aortic constriction for 4 weeks. In a Langendorff model, hypertrophic hearts were subjected to 40 min/60 min I/R or with IPostC intervention consisting of 6 cycles of 10 s reperfusion and 10 s no-flow before a 60-min reperfusion. Hemodynamics, infarct size (IS), myocyte apoptosis and changes in expression of reperfusion injury salvage kinase (RISK) pathway were examined. RESULTS: rAAV9-MEK1 gene delivery led to a 4.3-fold and 2.7-fold increase in MEK1 mRNA and protein expression in the heart versus their control values. I/R resulted in a larger IS in hypertrophic than in non-hypertrophic hearts (52.3 ± 4.7% vs. 40.0 ± 2.5%, P < 0.05). IPostC mediated IS reduction in non-hypertrophic hearts (27.6 ± 2.6%, P < 0.05), while it had no significant effect in hypertrophic hearts (46.5 ± 3.1%, P=NS) compared with the IS in non-hypertrophic or hypertrophic hearts subjected to I/R injury only, respectively. Hemodynamic decline induced by I/R was preserved by IPostC in non-hypertrophic hearts but not in hypertrophic hearts. rAAV9-MEK1 gene delivery restored IPostC protection in hypertrophic hearts evidenced by reduced IS (32.0 ± 2.8% vs. 46.5 ± 3.1%) and cardiac cell apoptosis and largely preserved hemodynamic parameters. These protective effects were associated with significantly increased phosphorylation of ERK1/2 and ribosomal protein S6 kinases (p70S6K), but it had no influence on Akt and glycogen synthase kinase-3ß. CONCLUSION: These results demonstrated that rAAV9-mediated activated MEK1 expression restores IPostC protection in the hypertrophic heart against I/R injury through the activation of ERK pathway.

MIF -173G/C (rs755622) polymorphism modulates coronary artery disease risk: evidence from a systematic meta-analysis.

BACKGROUND: Coronary artery disease (CAD) remains one of the major causes of death in humans. Genetic testing may allow early detection and prevention of this disease. This study aimed to investigate the association between the macrophage migration inhibitory factor (MIF) -173G/C (rs755622) polymorphism and susceptibility to CAD based on a meta-analysis. METHODS: We searched several databases to identify observational case-control studies investigating the association between the MIF -173G > C (rs755622) polymorphism and CAD risk published before July 30, 2019. Data were analyzed using the STATA software. RESULTS: Six studies, comprising a total of 1172 CAD cases and 1564 controls evaluated for MIF polymorphisms, were included. The occurrence of CAD was found to be associated with the C allele of the MIF rs755622 SNP in the total population (C/G, OR = 1.489, 95% CI = 1.223-1.813). Further, MIF -173G/C polymorphism was significantly associated with CAD under the allelic model in the Asian (C/G, OR = 1.775, 95% CI = 1.365-2.309) and Caucasian (C/G, OR = 1.288, 95% CI 1.003-1.654) subgroups. The data showed that the risk of CAD was higher in the population carrying the C allele. CONCLUSIONS: We found evidence of associations between MIF -173C/G and CAD susceptibility in the Asian and Caucasian populations.

Hyperuricemia and its association with adiposity and dyslipidemia in Northwest China: results from cardiovascular risk survey in Xinjiang (CRS 2008-2012).

BACKGROUND: Hyperuricemia predisposes to gout, which may result in tophi, kidney stones, or urate nephropathy even kidney failure. Many metabolic risk factors and disorders has been recognized as a key risk factor contributing to development of hyperuricemia. AIM: To determine the prevalence of hyperuricemia and its association with adiposity and dyslipidemia. METHODS: We recruited non-hospitalized participants (aged ≥35 years) in Xinjiang, a northwest part of China based on the Cardiovascular Risk Survey (CRS 2008-2012). Information of general health status, seafood or internal organs intake and history of disease were obtained by using an interview-based questionnaire. The levels of serum uric acid (sUA) and creatinine and lipid profiles were measured. A multivariate logistic regression model was performed to assess the association between prevalence of hyperuricemia and adiposity and dyslipidemia. RESULTS: This study recruited 16,611 participants, and 14,618 was included (mean age of 50.5 ± 12.6 years, 46.6% was males). The study population comprised three ethnic groups with 39.4% of Han, 32.6% of Uygur and 28% of Kazakh Chinese. The overall prevalence of hyperuricemia was 9.1% (95% CI: 8.6 to 9.6) and it was11.8% in men was 6.7% in women. The three ethnic groups also had different hyperuricemia prevalence with 15.4% in Han, 4.6% in Uygur and 5.5% in Kazakh Chinese, which corresponding to a respective mean sUA levels of 306.2 ± 86.9, 249.4 ± 76.1 and 259.8 ± 78.7 µmol/L. Participants with diabetes, hypertension or hypertriglyceridemia and higher blood urea nitrogen (BUN), estimated glomerular filtration rate (eGFR), fasting blood glucose (FBG), triglycerides (TG), total cholesterol (TC) had higher levels of sUA (P < 0.001 respectively). Multivariate logistic regression analysis revealed that age, gender, ethnicity, drinking, obesity, waist circumference, TG (≥2.26 mmol/L), TC (≥6.22 mmol/L) are major risk factors for hyperuricemia. Compared to the 35-44-year age group [adjusted odds ratio (AOR) = 1], the risk of hyperuricemia increased 1.61-fold in the 65-74-year age group (AOR = 1.61, 95% CI: 1.34-1.91; P < 0.001), and 1.71-fold in the 75- and older age group (AOR = 1.71, 95% CI: 1.27-2.29; P < 0.001). There was a 1.45-fold higher risk of hyperuricemia in men (AOR = 1.45, 95% CI: 1.24-1.68; P < 0.001) compared to women. Further, the risk of hyperuricemia increased significantly with drinking (AOR = 1.36; 95% CI: 1.16-1.61; P < 0.001), overweight (AOR = 1.25; 95% CI: 1.06-1.48; P = 0.01), obesity (AOR = 1.28; 95% CI: 1.10-1.49; P < 0.001), waist circumference (AOR = 1.48; 95% CI: 1.24-1.78; P < 0.001), TC (≥6.22 mmol/L, AOR = 1.45; 95% CI: 1.19-1.75; P < 0.001), TG (≥2.26 mmol/L, AOR = 2.74; 95% CI: 2.39-3.14; P < 0.001). CONCLUSIONS: These findings documented that the hyperuricemia is prevalent in the economically developing regions of northwest China. Hyperuricemia is associated with advanced age, male ender and general metabolic and cardiovascular risk factors. Obesity and dyslipidemia increase the risk of hyperuricemia.

TBL2 methylation is associated with hyper-low-density lipoprotein cholesterolemia: a case-control study.

BACKGROUND: HMGCR, SCAP, SREBF1, SREBF2 and TBL2 are well-known genes that are involved in the process of lipid metabolism. However, it is not known whether epigenetic changes of these genes are associated with lipid metabolism. In this study, the methylation levels of the HMGCR, SCAP, SREBF1, SREBF2 and TBL2 genes were analyzed between samples from a hyper-low-density lipoprotein cholesterolemia (hyper-LDL) group and a control group to examine the association between the methylation levels of these genes and the risk of hyper-LDL. METHODS: In this study, a case-control approach was used to explore the association between DNA methylation and hyper-LDL. The DNA methylation levels of HMGCR, SCAP, SREBF1, SREBF2 and TBL2 genes and 231 CpG sites in the promoter regions of these genes were measured in 98 hyper-LDL participants and 89 participants without hypo-LDL. RESULTS: Compared with participants without hyper-LDL, patients with hyper-LDL TBL2 gene had lower methylation levels (11.93 vs. 12.02, P = 0.004). The methylation haplotypes with significant abundance in the TBL2 gene are tcttttttttt (P = 0.034), ctttttttcct (P = 0.025), ctctttctttt (P = 0.040), ccttttttttt (P = 0.028), and tctttttttttttttt. CONCLUSION: The study demonstrates that participants with hyper-LDL have lower methylation of TBL2. The results suggest that DNA methylation of TBL2 can decrease the risk for hyper-LDL in humans.

Overexpression of IκBα in cardiomyocytes alleviates hydrogen peroxide-induced apoptosis and autophagy by inhibiting NF-κB activation.

BACKGROUND: Inflammation and oxidative stress play predominant roles in the initiation and progression of ischaemia/reperfusion (I/R) injury, with nuclear factor kappa B (NF-κB) serving as a crucial mediator. Overexpression of the inhibitor of κB alpha (IκBα) gene is hypothesized to have protective effects against apoptosis and autophagy in cardiomyocytes subjected to hydrogen peroxide (H2O2) by inhibiting the NF-κB pathway. METHODS: The IκBαS32A, S36A gene was transfected via adeno-associated virus serotype 9 (AAV9) delivery into neonatal rat ventricular cardiomyocytes (NRVMs) prior to H2O2 treatment. NRVMs were divided into control, H2O2, GFP + H2O2, IκBα+H2O2, and pyrrolidine dithiocarbamate (PDTC) + H2O2 groups. Nuclear translocation of the NF-κB p65 subunit was evaluated by immunofluorescence and Western blotting. Cell viability was assessed by Cell Counting Kit-8 assay. Supernatant lactate dehydrogenase (LDH) and intracellular malondialdehyde (MDA) were measured to identify H2O2-stimulated cytotoxicity. Apoptosis was determined by Annexin V-PE/7-AAD staining, and the mitochondrial membrane potential (ΔΨm) was detected by JC-1 staining. Western blotting was used to detect apoptosis- and autophagy-related proteins. RESULTS: IκBα transfection significantly increased cell viability and ΔΨm but decreased the supernatant LDH and cellular MDA levels in cardiomyocytes exposed to H2O2. Meanwhile, IκBα overexpression decreased H2O2-induced apoptosis by upregulating the Bcl-2/Bax ratio and reduced autophagy by downregulating the expression of Beclin-1 and the LC3-II/LC3-I ratio. These effects partly accounted for the ability of IκBα to inhibit the NF-κB signalling pathway, as evidenced by decreases in p65 phosphorylation and nuclear translocation. Indeed, the effects of inactivation of NF-κB signalling with the specific inhibitor PDTC resembled the cardioprotective effects of IκBα during H2O2 stimulation. CONCLUSION: IκBα overexpression can ameliorate H2O2-induced apoptosis, autophagy, oxidative injury, and ΔΨm loss through inhibition of the NF-κB signalling pathway. These findings suggest that IκBα transfection can result in successful resistance to oxidative stress-induced damage by inhibiting NF-κB activation, which may provide a potential therapeutic target for the prevention of myocardial I/R injury.