Left ventricular remodeling and its correlation with serum cardiac troponin I in patients with end-stage renal disease treated.

OBJECTIVE: To investigate the effects of different blood purification modes on left ventricular remodeling and its relationship with serum cardiac troponin I (cTnI) in patients with end-stage renal disease (ESRD). METHOD: A total of 108 patients with ESRD were selected, 55 cases were divided into hemodialysis combined with hemoperfusion (HD + HP) group, in which patients participants accepted routine hemodialysis for three times/week and hemoperfusion for three times/month; 53 cases in hemodialysis combined with hemodialysis filtration (HD + HDF) group, routine hemodialysis three times/week + hemodialysis filtration three times/month. The total duration of dialysis in the study was 1 year. Cardiac troponin I (cTnI) levels were measured before dialysis and 1 year after treatment, and related parameters were measured by echocardiography, including ventricular septal thickness (IVST), left ventricular posterior wall thickness (LVPWT), left ventricular end diastolic diameter (LVEDd), left ventricular end systolic diameter (LVEDs), and left ventricular myocardial mass index (LVMI). The paired t test was used within the group. Correlation analysis was performed using Spearman correlation analysis. RESULT: After treatment, the levels of cTnI, IVST, LVPWT, LVEDd, LVEDs, and LVMI in the two groups were increased, and the results were statistically significant (all p < 0.05). In addition, cTnI of the two groups was significantly correlated with IVST, LVPWT, LVEDd, LVEDs, and LVMI (all p < 0.05). CONCLUSION: Left ventricular remodeling is common in patients with ESRD, HD + Hp, and HD + HDF cannot reduce the phenomenon of left ventricular remodeling, cTnI can be used as a predictor of left ventricular hypertrophy and enlargement.

Four case reports of left anterior descending restenosis treated via the internal mammary artery: A literature review.

Objective: To analyse four cases of intervention via the internal mammary artery-anterior descending branch and provide and summarise the clinical treatment experience. Methods: The clinical data of four patients with distal restenosis of a left anterior descending artery (LAD) anastomosis after left internal mammary artery (LIMA)-LAD bypass surgery, who were admitted to the Gansu Institute of Cardiovascular Diseases between March 2013 and April 2022, were retrospectively analysed and reviewed together with the relevant literature. Results: Among the four patients, one was treated with intracoronary stenting via the internal mammary artery route, two were treated with intracoronary drug-coated balloon dilation (one of whom underwent fractional flow reserve [FFR] testing), and two underwent FFR testing (one of whom had a negative test result until the end of the procedure and continued to take medication during follow-up; the other patient had a positive result and further interventions). There were no deaths or postoperative complications in the group, and the patients were followed up for 4 months to 9 years, with good long-term outcomes. Conclusion: Percutaneous coronary intervention (PCI) via the internal mammary artery route is safe and effective, and patients with anastomotic distal stenosis or anastomotic stenosis of LAD bypass anastomosis may be considered for PCI via the internal mammary artery route.

Energy metabolism: A critical target of cardiovascular injury.

Cardiovascular diseases are the main killers threatening human health. Many studies have shown that abnormal energy metabolism plays a key role in the occurrence and development of acute and chronic cardiovascular diseases. Regulating cardiac energy metabolism is a frontier topic in the treatment of cardiovascular diseases. However, we are not very clear about the choice of different substrates, the specific mechanism of energy metabolism participating in the course of cardiovascular disease, and how to develop appropriate drugs to regulate energy metabolism to treat cardiovascular disease. Therefore, this paper reviews how energy metabolism participates in cardiovascular pathophysiological processes and potential drugs aimed at interfering energy metabolism.It is expected to provide good suggestions for promoting the clinical prevention and treatment of cardiovascular diseases from the perspective of energy metabolism.

Fractional flow reserve measured via left internal mammary artery after coronary artery bypass grafting: Two case reports.

BACKGROUND: The fractional flow reserve (FFR) has made the treatment of coronary heart disease more precise. However, there are few reports on the measurement of FFR via the left internal mammary artery (LIMA). Herein, we described the determination of further treatments by measuring FFR via the LIMA in 2 cases after coronary artery bypass grafting (CABG). CASE SUMMARY: Case 1 was a 66-year-old male who was admitted due to "chest tightness after CABG." The patient underwent CABG 7 years prior due to coronary heart disease. Coronary artery angiography showed complete occlusion of the left anterior descending artery (LAD), and subtotal occlusion of the third segment of the right coronary artery. On arterial angiography, there was 85% stenosis at the distal end of the anastomosis of the LIMA-LAD graft. FFR via LIMA was determined at 0.75. Thus, balloon dilation was performed in Case 1. FFR after balloon dilation was 0.94. Case 2 was a 60-year-old male who was admitted due to "chest tightness after CABG." The patient underwent CABG 6 years prior due to coronary heart disease. There was 60% segmental stenosis in the middle segment of LAD and 75% anastomotic stenosis. FFR measured via LIMA was 0.83 (negative); thus the intervention was not performed. Case 2 was given drug treatments. At the 3-mo follow-up, there was no recurrence of chest tightness or shortness of breath in both cases. They are currently under continual follow-up. CONCLUSION: We provided evidence that FFR measurement via grafted blood vessels, especially LIMA, after CABG is a good method to determine the intervention course.

Association between ambient temperature and cardiovascular diseases related hospital admissions in Lanzhou, China.

Cardiovascular disease (CVD) remains the leading cause of morbidity and mortality worldwide, ranking first in the global disease burden. Evidence on association between temperature and cardiovascular disease is insufficient and inconsistent in developing countries. In this study, a distributed lag nonlinear model (DLNM) was used to determine the association between daily mean temperature and cardiovascular diseases (CVD) related admission in Lanzhou 2015-2019. We included 41,389 patients with CVD in this study. The relative risk (RR) of CVD admission increased significantly with temperature in lag 5-10 days, and we found harvesting effect of temperature in the study, shown as decreased RR in lag 15-30 days. The maximum RR was 1.15 (95% confidence interval [CI]: 1.03-1.30), corresponding to 24 °C. Both cold and heat effects of temperature could impact the CVD admission. Compared with the 25th percentile of temperature (2 °C), the cumulative relative risk (cumRR) of extreme cold (-5 °C, the 2.5th percentile of the temperature) was 0.69 (95% CI: 0.51-0.94) in lag 0-14, whereas the cumRR of moderate cold (-2 °C, the 10th percentile) was 0.83 (95% CI:0.71-0.97). Compared with the 75th percentile of temperature (20-°C), the cumRR of extreme heat (27 °C, the 97.5th percentile) was 0.93 (95% CI: 0.78-1.10) in lag 0, whereas the cumRR of moderate heat (24 °C, the 90th percentile) was 1.01 (95% CI: 0.94-1.08). In the stratified analysis, cold decreased RR significantly in female and ≥65 years, whereas heat increased it more obviously in male and ≥65 years. Ambient temperature and CVD admissions were positively associated, with the harvesting effect. Our findings demonstrate the adaption of residents in Lanzhou to cold temperature. Public and environmental policies and measures aimed at moderate heat may minimize CVD burden effectively.

A Functional Variant Rs492554 Associated With Congenital Heart Defects Modulates SESN2 Expression Through POU2F1.

Hypoxia exposure is responsible for the high incidence of congenital heart defects (CHDs) in high-altitude areas, which is nearly 20 times higher than that in low-altitude areas. However, the genetic factors involved are rarely reported. Sestrin2 (SESN2), a hypoxia stress-inducible gene, protects cardiomyocyte viability under stress; thus, SESN2 polymorphism may be a potential risk factor for CHD. We performed an association study of the SESN2 polymorphisms with CHD risk in two independent groups of the Han Chinese population from two different altitude areas. The allele-specific effects of lead single-nucleotide polymorphisms (SNPs) were assessed by expression quantitative trait locus, electrophoretic mobility shift, and luciferase reporter assays. The molecular mechanism of Sesn2 action against hypoxia-induced cell injury was investigated in embryonic rat-heart-derived H9c2 cells treated with or without hypoxia-mimetic cobalt chloride. SNP rs492554 was significantly associated with reduced CHD risk in the high-altitude population, but not in the low-altitude population. The protective T allele of rs492554 was correlated with higher SESN2 expression and showed a preferential binding affinity to POU2F1. We then identified SNP rs12406992 in strong linkage disequilibrium with rs492554 and mapped it within the binding motif of POU2F1. The T-C haplotype of rs492554-rs12406992 could increase luciferase expression, whereas POU2F1 knockdown effectively suppressed it. Mechanistically, increased Sesn2 protects against oxidative stress and cell apoptosis and maintains cell viability and proliferation. In summary, CHD-associated SNP rs492554 acts as an allele-specific distal enhancer to modulate SESN2 expression via interaction with POU2F1, which might provide new mechanistic insights into CHD pathogenesis.

CCN1 gene polymorphisms associated with congenital heart disease susceptibility in Northwest Chinese population from different high-altitude areas.

High-altitude hypoxic environment exposure is considered one of the risk factors for congenital heart disease (CHD), but the genetic factors involved are still unclear. CCN1, one of the synergistic molecules in the hypoxic response, is also an indispensable molecule in cardiac development. Considering that CCN1 may play an important role in the occurrence of CHD in high-altitude areas, we investigated the association between CCN1 polymorphisms and CHD susceptibility in Northwest Chinese population from different high-altitude areas. We conducted a case-control study with a total of 395 CHD cases and 486 controls to evaluate the associations of CCN1 polymorphisms with CHD risk. Our results showed that the protective alleles rs3753793-C (OR = 0.59, 95% CI = 0.42-0.81, P = 0.001), rs2297141-A (OR = 0.66, 95% CI = 0.49-0.90, P = 0.001), and C-A haplotype of rs3753793-rs2297141 (OR = 0.58, 95% CI = 0.42-0.82, P = 0.002) were significantly associated with a decreased atrial septal defect (ASD) risk. Further subgroup analysis in different geography populations revealed robust association of SNP rs2297141 with ASD risk in a Han population residing in high altitude of 2500-4287 m. We also found that the frequency of protective alleles was higher in high-altitude population, and the alleles were responsible for the difference of oxygen physiology-related erythrocyte parameters in different high-altitude populations. rs3753793-C and rs2297141-A are likely related to high altitude and hypoxia adaptation, which may also be the reason for the association between CCN1 polymorphism and ASD risk.

Dickkopf­1/cysteine­rich angiogenic inducer 61 axis mediates palmitic acid­induced inflammation and apoptosis of vascular endothelial cells.

Cardiovascular diseases (CVDs) are a major cause of mortality around the world, and the presence of atherosclerosis is the most common characteristic in patients with CVDs. Cysteine­rich angiogenic inducer 61 (CCN1) has been reported to serve an important role in the pathogenesis of atherosclerotic lesions. The aim of the present study was to investigate whether CCN1 could regulate the inflammation and apoptosis of endothelial cells induced by palmitic acid (PA). Dickkopf­1 (DKK1) is an important antagonist of the Wnt signaling pathway, which can specifically inhibit the classic Wnt signaling pathway. Firstly, the mRNA and protein expression levels of CCN1 were detected. Additionally, endothelial nitric oxide (NO) synthase (eNOS), DKK1, ß­catenin, and inflammation­ and apoptosis­associated proteins were measured. Detection of NO was performed using a commercial kit. The expression levels of inflammatory cytokines were assessed to explore the effect of CCN1 on PA­induced inflammation. TUNEL assay was used to detect the apoptosis of endothelial cells. The results revealed that PA upregulated the expression levels of CCN1, inflammatory cytokines and pro­apoptotic proteins in endothelial cells. PA decreased the production of NO, and the levels of phosphorylated­eNOS, whereas knockdown of CCN1 partially abrogated these effects triggered by PA. Furthermore, the Wnt/ß­catenin signaling pathway was activated in PA­induced endothelial cells; however, the levels of DKK1 were downregulated. Overexpression of DKK1 could reduce CCN1 expression via inactivation of the Wnt/ß­catenin signaling pathway. In conclusion, knockdown of CCN1 attenuated PA­induced inflammation and apoptosis of endothelial cells via inactivating the Wnt/ß­catenin signaling pathway.

Overexpression of lncRNA Dancr inhibits apoptosis and enhances autophagy to protect cardiomyocytes from endoplasmic reticulum stress injury via sponging microRNA-6324.

Endoplasmic reticulum stress (ERS) contributes to the pathogenesis of myocardial ischemia/reperfusion injury and myocardial infarction (MI). Long non-coding RNAs (lncRNAs) serve an important role in cardiovascular diseases, and lncRNA discrimination antagonizing non-protein coding RNA (Dancr) alleviates cardiomyocyte damage. microRNA (miR)-6324 was upregulated in MI model rats and was predicted to bind to Dancr. The present study aimed to investigate the role of Dancr in ERS-induced cardiomyocytes and the potential underlying mechanisms. Tunicamycin (Tm) was used to induce ERS. Cell viability, apoptosis and levels of associated proteins, ERS and autophagy in Dancr-overexpression H9C2 cells and miR-6234 mimic-transfected H9C2 cells were assessed using Cell Counting Kit-8, TUNEL staining and western blot assay, respectively. The results suggested that Dancr expression levels and cell viability were downregulated by Tm in a concentration-dependent manner compared with the control group. Tm induced apoptosis, ERS and autophagy, as indicated by an increased ratio of apoptotic cells, increased expression levels of Bax, cleaved (c)-caspase-3/9, glucose-regulated protein 78 kDa (GRP78), phosphorylated (p)-inositol-requiring enzyme-1α (IRE1α), spliced X-box-binding protein 1 (Xbp1s), IRE1α, activating transcription factor (ATF)6, ATF4, Beclin 1 and microtubule associated protein 1 light chain 3α (LC3)II/I, and decreased expression levels of Bcl-2, unspliced Xbp1 (Xbp1u) and p62 in the Tm group compared with the control group. Moreover, the results indicated that compared with the Tm + overexpression (Oe)-negative control (NC) group, the Tm + Oe-Dancr group displayed decreased apoptosis, but enhanced ERS and autophagy to restore cellular homeostasis. Compared with the Tm + Oe-NC group, the Tm + Oe-Dancr group decreased the ratio of apoptotic cells, decreased expression levels of Bax, c-caspase-3/9 and Xbp1u, and increased expression levels of Bcl-2, p-IRE1α, Xbp1s, Beclin 1 and LC3II/I. Dancr overexpression also significantly downregulated miR-6324 expression compared with Oe-NC. The dual-luciferase reporter assay further indicated an interaction between Dancr and miR-6324. In addition, miR-6324 mimic partially reversed the effects of Dancr overexpression on Tm-induced apoptosis, ERS and autophagy. In conclusion, lncRNA Dancr overexpression protected cardiomyocytes against ERS injury via sponging miR-6324, thus inhibiting apoptosis, enhancing autophagy and restoring ER homeostasis.

A SNP involved in alternative splicing of ABCB1 is associated with clopidogrel resistance in coronary heart disease in Chinese population.

Although many scientists are studying the association between genetic polymorphism of ABCB1 and CR in patients, the molecular mechanism has not been further studied in patients with CHD. This study investigated the relationship between SNP of the ABCB1 gene in patients with CHD and CR, and whether the polymorphism of the ABCB1 gene affects the AS of the gene. 741 patients were enrolled in the study, 316 CR cases and 425 NCR cases. The correlation between CR risk and clinical-pathological characteristics were studied. Additionally, the five SNPs were analysed by PCR and Mass Array genotyping methods. Furthermore, silicon analysis was used to predict whether the polymorphism affects the process of AS. Results showed that there was a significant correlation between rs1045642 polymorphism and CR in genotyping and allele analysis. The rs1045642 polymorphism of the ABCB1 gene of CHD patients carrying the A allele are more likely to develop CR. Silicon analysis showed that rs1045642 generated a new ESE sequence which might affect AS of ABCB1 gene. We hypothesize that the mechanism of CR might be caused by a change in the AS caused by the polymorphism of the gene. Thus, this work provides guidance for the clinical use of clopidogrel.

Angiopoietin-like protein 7 mediates TNF-α-induced adhesion and oxidative stress in human umbilical vein epithelial cell.

Tumor necrosis factor-α (TNF-α) promotes monocyte adhesion to endothelium and accumulation of endothelium will lead to atherosclerosis. The present study explored Angiopoietin-like protein (Angptl7) as a potential target in the process of atherosclerosis, and its role in the adhesion and oxidative stress induced by TNF-α in human umbilical vein epithelial cells (HUVEC). The initiation of atherosclerosis is endothelial injury. Angptl7 was dramatically increased in TNF-α-induced HUVEC compared to the control cells. After Angptl7 effectively knocked-down in TNF-α-induced HUVEC, the levels of reactive oxygen species (ROS), interleukin (IL)-1ß, IL-6 and cyclooxygenase-2 (Cox-2) were prominently decreased, whereas the levels of nitric oxide (NO) and endothelia nitric oxide synthase (eNOS) were increased. Inhibition of Angptl7 significantly reversed TNF-α-induced cell adhesion in HUVEC. Finally, downregulation of Angptl7 significantly reduced the expression of nuclear factor-κB (NF-κB) and enhanced the levels of nuclear factor erythroid 2-related factor 2 (Nrf-2) and heme oxygenase-1 (HO-1) in TNF-α-treated HUVEC. Angptl7 conducted TNF-α-induced oxidative stress and cell adhesion in HUVEC. Therefore, Angptl7 might participate in the development of endothelial injury and further atherosclerosis. This might give us a new insight for investigation of procession of atherosclerosis.

A novel homozygous FBXO43 mutation associated with male infertility and teratozoospermia in a consanguineous Chinese family.

OBJECTIVE: To identify the genetic causes of male infertility characterized by teratozoospermia. DESIGN: Genetic studies. SETTING: Medical university. PATIENT(S): Two infertile brothers with teratozoospermia in a consanguineous Chinese family, another 124 sporadic infertile male patients presenting with teratozoospermia, and 200 male controls with normal fertility. INVENTION(S): None. MAIN OUTCOME MEASURE(S): Whole exome sequencing and genotype analysis to identify the potential pathogenic mutation, Sanger sequencing to validate the mutation in family members, in silico structural modeling to predict the functional consequences of mutation, and targeted next-generation sequencing to validate the mutation in sporadic cases. RESULT(S): A novel homozygous nonsynonymous mutation (C1991T, p.G664D) in FBXO43 (F-box only protein 43) was observed in two brothers from a consanguineous Chinese family. The mutation was segregated with the disease phenotype and was predicted to be a disease causing protein by SIFT, PolyPhen-2, and Mutation Taster. An in silico mutant FBXO43 model predicts that the mutation p.G664D causes shortening of two ß-sheets, an additional α-helix, and change in loops, which may result in loss of function of the protein. The homozygous mutation of FBXO43 was absent in the 1000 Genomes Project (1000 G) and the Exome Aggregation Consortium (ExAC) databases. Subsequent mutation screening of FBXO43 in a cohort of 124 cases identified four additional cases with heterozygous FBXO43 mutations. No mutations were found in FBXO43 in 200 fertile controls. CONCLUSION(S): The mutation in FBXO43 is a causative factor of male infertility and teratozoospermia.

Teratozoospermia with amorphous sperm head associate with abnormal chromatin condensation in a Chinese family.

Male infertility affects approximately 7% of the male population. In about 40% of affected patients, the etiology remains unknown. Here, we report the cases of two infertile brothers who have a uniquely prevalent sperm phenotype with completely amorphous sperm heads. To investigate the mechanisms of familial teratozoospermia with amorphous sperm heads, chromatin condensation was assessed by aniline blue staining, western blot, sperm chromatin structure assay and atomic force microscopy in both the two brothers and 40 control fertile donors. Our results showed an abnormal condensation of chromatin with amorphous headed sperm. We suggest that abnormal chromatin condensation which was induced by disturbances in the process of histone-protamine replacement may be a possible cause of familial teratozoospermia with amorphous head, and the elasticity of sperm nuclei could be a new index to assess sperm quality. Additionally, for the first time, the current study provided a new biomechanics strategy for evaluating pathological sperm contributes to our understanding of teratozoospermia.Abbreviations: SCSA: sperm chromatin structure assay; AFM: atomic force microscopy; ICSI: intracytoplasmic sperm injection; HDS: high DNA stainability; DFI: DNA fragmentation index; PBS: phosphate-buffered saline; DTT: dithiothreitol; FITC: fluorescein isothiocyanate; DAPI: 4',6-diamidino-2-pheneylindole; SSC: standard saline citrate.

The curative effect of synthetic treatment for refractory acute myocardial infarction.

BACKGROUND: This study aims to investigate the curative effect of synthetic treatment for refractory acute myocardial infarction (AMI). METHODS: A total of 76 patients with coronary AMI accompanied by shock, who were treated with combined therapy from August 1999 to April 2017, were included into this study. Sixty patients received emergency percutaneous coronary intervention (PCI). Among these patients, 39 patients received intra-aortic balloon counterpulsation (IABP), eight patients had failed PCI underwent emergency off-pump coronary artery bypass (E-OPCAB), and eight patients were treated by hybrid cardiac surgery. RESULTS: All patients were successfully rescued. However, two patients died afterward due to postoperative complications. CONCLUSIONS: For AMI patients complicated with shock, especially when emergency PCI fails or is difficult to perform, PCI + IABP, emergency E-OPCAB and hybrid cardiac surgery should be carried out, in order to achieve a good outcome and improve the success rate of rescue for this group of patients. KEYWORDS: Acute myocardial infarction (AMI); emergency percutaneous coronary intervention (PCI); intra-aortic balloon counterpulsation (IABP); emergency off-pump coronary artery bypass (E-OPCAB); hybrid cardiac surgery.

A genetic variant in a homocysteine metabolic gene that increases the risk of congenital cardiac septal defects in Han Chinese populations.

Elevated homocysteine levels are known to be a risk factor for congenital cardiac septal defects (CCSDs), but the mechanism underlying this effect is unknown. The genetic variants that were significantly associated with circulating homocysteine concentrations have been systematically identified through the genome-wide association studies of one-carbon core metabolites. To examine the role of the genome-wide significant homocysteine related variants in the occurrence of CCSDs, we investigated the association between these variants and CCSDs in Han Chinese populations. Five variants of the genome-wide significant homocysteine-related genes were selected for analysis in two stages of case-controlled studies with a total of 904 CCSD patients and 997 controls. SYT9 expression was detected in human cardiovascular tissue using qRT-PCR. The intronic variant rs11041321 of the SYT9 gene was associated with an increased risk of developing CCSDs in both the separate and combined case-controlled studies. Combined samples from the two stage cohorts had a significant elevation in CCSD risk for the T allele (OR = 1.43, P = 2.6 × 10-6 ), CT genotype and TT genotype (CT: OR = 1.30, TT: OR = 2.21; P = 1 × 10-4 ) compared with the wild-type C allele and CC genotype, respectively. The risky T allele carriers exhibited decreased SYT9 mRNA expression, compared with wild-type C allele carriers. The intronic SYT9 variant rs11041321, which exhibits a significant genome-wide association with circulating homocysteine, was associated with the occurrence of CCSDs. This finding helps to characterize the unexpected role of SYT9 in homocysteine metabolism and the development of CCSDs, which further highlighted the interplay of diet, genetics, and human birth defects. © 2017 IUBMB Life, 69(9):700-705, 2017.

Alcohol Consumption and Breast Cancer Survival: A Meta- analysis of Cohort Studies.

BACKGROUND AND OBJECTIVES: Evidence for associations between alcohol consumption with breast cancer survival are conflicting, so we conducted the present meta-analysis. METHODS: Comprehensive searches were conducted to find cohort studies that evaluated the relationship between alcohol consumption with breast cancer survival. Data were analyzed with meta-analysis software. RESULTS: We included 25 cohort studies. The meta-analysis results showed that alcohol consumption was not associated with increased breast cancer mortality and recurrence after pooling all data from highest versus lowest comparisons. Subgroup analyses showed that pre-diagnostic or post-diagnostic consumpotion, and ER status did not affect the relationship with breast cancer mortality and recurrence. Although the relationships of different alcohol consumption with breast cancer mortality and recurrence were not significant, there seemed to be a dose-response relationship of alcohol consumption with breast cancer mortality and recurrence. Only alcohol consumption of >20 g/d was associated with increased breast cancer mortality, but not with increased breast cancer recurrence. CONCLUSION: Although our meta-analysis showed alcohol drinking was not associated with increased breast cancer mortality and recurrence, there seemed to be a dose-response relationship of alcohol consumption with breast cancer mortality and recurrence and alcohol consumption of >20 g/d was associated with increased breast cancer mortality.