His potential injury as the end point of screwing by a continuous recording technique in His bundle pacing: A case report.

BACKGROUND: His bundle pacing (HBP) engaged electrical activation of both ventricles by stimulating the His-Purkinje network, which could avoid marked ventricles dyssynchrony. The lead was given three to five clockwise rotations at the site with the His potential to anchor the interventricular septum. In 2018, the Multicenter His Bundle Pacing Collaborative Working Group recommended that the His bundle capture threshold should be lower than 2.5 V/1 ms in non-pacing-dependent patients, and pacing-dependent patients should have a lower adjacent ventricular capture threshold as self-backup. Therefore, to avoid safety issues such as loss of capture caused by increased threshold, we believe that more stringent criteria should be adopted in patients with atrioventricular block (AVB). In previous studies, the connection cable needed to be disconnected during the screwing. When the procedure was finished, the performer found that the patients with His bundle injury could obtain a lower threshold than those without His bundle injury. Although no studies of new bundle branch block (BBB) or AVB by the acute His bundle injury was reported. However, It is worrying that the damage of His bundle seems random during the procedure. How to balance avoiding severe injury with a lower capture threshold? At present, we report a case of light His injury and lower His capture threshold under continuous intracardiac electrocardiogram monitoring.

Corrigendum: Guidance on left bundle branch pacing using continuous pacing technique and changes in lead V1 characteristics under real-time monitoring.

[This corrects the article DOI: 10.3389/fcvm.2023.1195509.].

An Electrochemical Perspective of Aqueous Zinc Metal Anode.

Based on the attributes of nonflammability, environmental benignity, and cost-effectiveness of aqueous electrolytes, as well as the favorable compatibility of zinc metal with them, aqueous zinc ions batteries (AZIBs) become the leading energy storage candidate to meet the requirements of safety and low cost. Yet, aqueous electrolytes, acting as a double-edged sword, also play a negative role by directly or indirectly causing various parasitic reactions at the zinc anode side. These reactions include hydrogen evolution reaction, passivation, and dendrites, resulting in poor Coulombic efficiency and short lifespan of AZIBs. A comprehensive review of aqueous electrolytes chemistry, zinc chemistry, mechanism and chemistry of parasitic reactions, and their relationship is lacking. Moreover, the understanding of strategies for suppressing parasitic reactions from an electrochemical perspective is not profound enough. In this review, firstly, the chemistry of electrolytes, zinc anodes, and parasitic reactions and their relationship in AZIBs are deeply disclosed. Subsequently, the strategies for suppressing parasitic reactions from the perspective of enhancing the inherent thermodynamic stability of electrolytes and anodes, and lowering the dynamics of parasitic reactions at Zn/electrolyte interfaces are reviewed. Lastly, the perspectives on the future development direction of aqueous electrolytes, zinc anodes, and Zn/electrolyte interfaces are presented.

Guidance on left bundle branch pacing using continuous pacing technique and changes in lead V1 characteristics under real-time monitoring.

Background: The changes in the morphology and characteristics of the V1 leads during left bundle branch capturing still need to be fully understood. Objective: This study aims to provide some suggestions about the LBB capture process through the morphology and characteristics of the V1 lead. Method: LBBP using the continuous pacing and morphology monitoring technique during screw-in using a revolving connector (John Jiang's connecting cable). The morphology and features of V1 leads are recorded by continuous monitoring technology. Results: The most common morphology in the LVSP stage is QR, while in the NS-LBBP (low output) stage and the NS-LBBP (lower output) stage, it is rSR. In the S-LBBP stage, it is rsR. The predominant morphology is with r/R waves in S-LBBP, which includes variations like rSR, rsR, rSr, rsr, rR, rs, rS, and R type, making up 96.7% of the total. The r waves in lead V1 are associated with agitated myocardium conducted from the left bundle branch. Conclusion: The initial r-wave in lead V1 may be a marker during the follow-up of patients with selective LBB capture.

Prophylactic Efficacy and Safety of Antithrombotic Regimens in Patients with Stable Atherosclerotic Cardiovascular Disease (S-ASCVD): A Bayesian Network Meta-Regression Analysis.

OBJECTIVE: The aim of this study was to evaluate the efficacy and safety of antithrombotic regimens and their combinations in preventing thrombotic incidents in patients with stable atherosclerotic cardiovascular disease (S-ASCVD). METHODS: A systematic literature search was conducted in the PubMed, Embase, Cochrane Library, Scopus, and Google Scholar databases. The primary comprehensive endpoint was a major adverse cardiovascular event (MACE) composite of cardiovascular death, stroke, or myocardial infarction, while the secondary endpoints were cardiovascular death, all-cause stroke, ischemic stroke, myocardial infarction, and all-cause death. The safety endpoint was major bleeding. Bayesian network meta-regression analysis in R software was used to calculate the final effect size and to correct for the effect of follow-up time on the outcome effect size. RESULTS: Twelve studies reporting 122,190 patients with eight antithrombotic regimens were included in this systematic review. For the primary composite endpoint, low-dose aspirin plus clopidogrel 75 mg (hazard ratio [HR] 0.53, 95% confidence interval [CI] 0.33-0.87) and low-dose aspirin plus rivaroxaban 2.5 mg twice daily (HR 0.53, 95% CI 0.34-0.82) showed significantly better efficacy than clopidogrel monotherapy, and the efficacy was comparable among the first two regimens. Unfortunately, none of the active regimens significantly decreased all-cause death, cardiovascular death branch, and all-cause stroke as part of the secondary endpoints. Low-dose aspirin plus ticagrelor 90 mg twice daily (HR 0.81, 95% CI 0.69-0.94) and low-dose aspirin plus ticagrelor 60 mg twice daily (HR 0.84, 95% CI 0.74-0.95) had a significant advantage in myocardial infarction compared with low-dose aspirin monotherapy, while low-dose aspirin plus 2.5 mg rivaroxaban twice daily (HR 0.62, 95% CI 0.41-0.94) was better than low-dose aspirin in the treatment of ischemic stroke. In the major bleeding branch, low-dose aspirin plus ticagrelor 90 mg twice daily (HR 2.2, 95% CI 1.70-2.90), low-dose aspirin plus ticagrelor 60 mg twice daily (HR 2.1, 95% CI 1.70-2.60), low-dose aspirin plus rivaroxaban 2.5 mg twice daily (HR 1.7, 95% CI 1.30-2.00), and rivaroxaban 5 mg twice daily (HR 1.5, 95% CI 1.20-1.90) showed higher major bleeding risk compared with low-dose aspirin. CONCLUSIONS: Considering MACEs, myocardial infarction, all kinds of stroke, ischemic stroke, and major bleeding, low-dose aspirin plus rivaroxaban 2.5 mg twice daily should be considered the preferred regimen for S-ASCVD patients with low bleeding risk.

Case report: Left bundle branch pacing guided by real-time monitoring of current of injury and electrocardiography.

Background: Left bundle branch (LBB) pacing (LBBP) has recently emerged as a physiological pacing mode. Current of injury (COI) can be used as the basis for electrode fixation position and detection of perforation. However, because the intermittent pacing method cannot monitor the changes in COI in real time, it cannot obtain information about the entire COI change process during implantation. Case summary: Left bundle branch pacing was achieved for treatment of atrioventricular block in a 76-year-old female. Uninterrupted electrocardiogram and electrogram were recorded on an electrophysiology system. In contrast to the interrupted pacing method, this continuous pacing and recording technique enables real-time monitoring of the change in ventricular COI and the paced QRS complex as the lead advances into the interventricular septum. During the entire screw-in process, the COI amplitude increased and then decreased gradually after reaching the peak, followed by a small but significant, rather than dramatic, decrease. Conclusion: This case report aims to demonstrate the clinical significance of changes in COI and QRS morphology for LBBP using real-time electrocardiographic monitoring and filtered and unfiltered electrograms when the lead is deployed using a continuous pacing technique. The technique could be used to confirm LBB capture and avoid perforation.

Evaluation of the shortening of the stimulus-to-peak left ventricular activation time at continuous low output to confirm left bundle branch capture.

Background: Left bundle branch area pacing (LBBAP) is a physiological pacing method for treatment of atrioventricular block. However, there is a need for a new convenient and safe method for performing left bundle branch pacing (LBBP) and to confirm left conduction system capture. Objective: This study aimed to explore a new convenient and safe method for performing selective LBBP. Methods: A total of 28 patients who had indications for pacing therapy and received LBBAP were recruited retrospectively. Demographic and baseline patient characteristics, electrocardiograms, pacing parameters, and intracardiac electrogram pattern were evaluated. Continuous unipolar pacing at low output (2 V / 0.5 ms) was performed during the whole period of LBBP lead implantation. Successful left bundle branch (LBB) capture was defined as the abrupt change of the pacing stimulus to the peak of R wave in lead V5 during continuous pacing at low output (2 V / 0.5 ms). Results: The parameters of the 2 shortenings (stimulus-to-peak left ventricular activation time [S-peak LVAT] before shortening, S-peak LVAT after shortening, and the duration of shortening) all showed a significant positive correlation (Pearson product-moment correlation coefficient [PCC] = 0.915, P < .001; PCC = 0.897, P < 0.001; PCCs = 0.765, P < 0.001). Shortening of the S-peak LVAT with continuous low output had a 100% sensitivity and 33.3% specificity for predicting stimulus-ventricular potential interval (S-V interval). Conclusion: Abrupt shortening of the S-peak LVAT at continuous low output was associated with abrupt shortening of the S-peak LVAT at low and high output. High rate of selective LBB capture can be achieved with the method of continuous low output, shortening the S-peak LVAT.

Electrophysiological characteristics and possible mechanism of bipolar pacing in left bundle branch pacing.

BACKGROUND: Left bundle branch pacing is a physiological pacing modality with a low and stable threshold. The electrophysiological characteristics and mechanisms of bipolar pacing remain unclear. OBJECTIVES: This study aimed to assess the electrophysiological characteristics of bipolar pacing of left bundle branch pacing and to infer the mechanisms underlying each electrocardiogram and electrogram waveform morphology. METHODS: A total of 65 patients who strictly met the criteria for left bundle branch capture were enrolled. The changes in the morphology of the electrocardiogram and electrogram during the threshold testing with different outputs on unipolar and bipolar pacing were recorded. The electrophysiological characteristics were then analyzed. RESULTS: Four distinct morphologies and 3 different types of transitions during bipolar pacing threshold testing were identified; we labeled the 4 types of morphologies as nonselective (NS)-bipolar-left bundle (LB), NS-cathodal-LB, selective (S)-cathodal-LB, and left ventricular septal-cathodal. Except left ventricular septal-cathodal, the other 3 types (NS-bipolar-LB, NS-cathodal-LB, and S-cathodal-L) had a short and constant V6 R-wave peak time (RWPT) (64.8 ± 7.7 ms vs 65.7 ± 7.8 ms vs 65.7 ± 7.3 ms). The paced QRS (P-QRS) complex was the narrowest in NS-bipolar-LB rather than in NS-cathodal-LB (118.2 ± 14.2 ms vs 133.8 ± 15.8 ms; P < .001). NS-bipolar-LB had a higher threshold than did NS-cathodal-LB (2.5 ± 1.2 V vs 0.8 ± 0.4 V; P < .001). CONCLUSION: With a higher output on bipolar pacing, NS-bipolar-LB capture had the shortest V6 RWPT, V1 RWPT, and P-QRS. S-cathodal-LB capture had the longest V1 RWPT and P-QRS complex.

Molecular Correlates of Early Onset of Diabetic Cardiomyopathy: Possible Therapeutic Targets.

Diabetes mellitus (DM) is associated with mitochondrial dysfunction and oxidative stress that can lead to diabetic cardiomyopathy (DCM), which can often remain undetected until late stages of the disease. However, myocardial injury occurs before the onset of measurable cardiac dysfunction, although its molecular correlates are poorly understood. In this study, we made a DM rat induced by a high-fat diet combined with low and high doses of streptozotocin (STZ) to emulate pre and early DCM. RNA-sequencing analysis of ventricular tissue revealed a differential transcriptome profile and abnormal activation of pathways involved in fatty acid metabolism, oxidative phosphorylation, cardiac structure and function, insulin resistance, calcium signalling, apoptosis, and TNF signalling. Moreover, using high glucose-treated human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CM), we recapitulated the cardiac cellular phenotype of DM and identified several molecular correlates that may promote the development of DCM. In conclusion, we have developed an experimental framework to target pathways underlying the progression of DCM.

High-pass filter settings and the role and mechanism of discrete ventricular electrograms in left bundle branch pacing.

Objective: The characteristics of discrete intracardiac electrogram (EGM) in selective left bundle branch (SLBB) pacing (SLBBP) have not been described in detail previously. This study aimed to examine the effect of different high-pass filter (HPF) settings on discrete local ventricular components in an intracardiac EGM and to analyze its possible mechanisms. Methods: This study included 144 patients with indications of permanent cardiac pacing. EGMs were collected at four different HPF settings (30, 60, 100, and 200 Hz) with a low-pass filter at 500 Hz, and their possible mechanisms were analyzed. Results: LBBP was successfully achieved in 91.0% (131/144) of patients. SLBBP was achieved in 123 patients. The occurrence rates of discrete local ventricular EGM were 16.7, 33.3, 72.9, and 85.4% for HPF settings of 30, 60, 100, and 200 Hz, respectively. The analysis of discrete EGM detection showed significant differences between the different HPF settings. By using the discrete local ventricular component and isoelectric interval as the SLBB capture golden standard, the results of EGMs revealed that the 30 Hz HPF has a sensitivity of 19% and specificity of 100%. The 60 Hz HPF had a sensitivity of 39% and a specificity of 100%. The 100 Hz HPF had a sensitivity of 85% and a specificity of 100%. The 200 Hz HPF had a sensitivity of 100% and specificity of 100%. Conclusion: An optimal HPF setting of 200 Hz is recommended for discrete local ventricular EGM detection. A discrete local ventricular EGM should exhibit an isoelectric interval. A steep deflection and high-frequency ventricular EGM morphology nearly identify an intrinsic EGM morphology.

The Interdiffusion Behavior of NiCoCrAlYHf Coating Deposited by Arc Ion Plating on Carburized Ni-Based Single Crystal Superalloy.

In the present study, arc ion plating (AIP) was used to prepare a NiCoCrAlYHf coating (HY5 coating) on a carburized third-generation single-crystal superalloy DD10. The interdiffusion behavior of the carburized superalloy with an HY5 coating was investigated for a 1000 h oxidation time at 1100 °C. Carburization enhanced the interfacial bonding force and improved the microstructure of the NiCoCrAlYHf coating. An interdiffusion zone (IDZ) formed after a 300 h oxidation time, and the formation of a carburized layer effectively suppressed an inward diffusion of cobalt, aluminium, and chromium to the DD10 superalloy as well as an outward diffusion of nickel and refractory elements for instance rhenium and tungsten to the HY5 coating that occurred in static air at 1100 °C. The roles of the carburized layer in affecting thermal cyclic oxidation and element interdiffusion were studied. Subsequently, a modified form of the Boltzmann-Matano analysis was used to present the interdiffusion coefficients of aluminium.

Gene polymorphisms of insulin secretion signaling pathway associated with clopidogrel resistance in Han Chinese population.

BACKGROUND: Due to the loss of responsiveness to insulin, diabetes mellitus (DM) patients develop increased platelet reactivity and reduced response to antiplatelet agents. Nevertheless, the relationship between the single-nucleotide polymorphisms (SNP) of the signal pathway gene of insulin secretion and the effect of clopidogrel is elusive. METHODS: Blood samples were collected from patients administered with dual-antiplatelet therapy (clopidogrel, 75 mg, once daily and aspirin, 100 mg, once daily) after 5 days and completed test within 4 h. The VerifyNow P2Y12 assay was used to measure the platelet functions, and the results were expressed as a P2Y12 reaction unit (PRU). Notably, the selected SNPs were analyzed to demonstrate the functionality of genetic variants. RESULTS: Analysis of the study population showed that old age, lower plasma albumin (ALB) level, higher creatinine (CREA) level, higher uric acid (UA) level, lower platelet (PLT) count, and lower plateletcrit (PCT) potentially increased the risk of clopidogrel resistance. In a single-nucleotide polymorphism rs6056209 of the PCLB1 gene, the AG genotype was a risk factor for clopidogrel resistance (p < 0.05, OR = 1.574). Similarly, the CC and AG genotype in GNAS rs7121 and CCKAR rs1800857 were protective factors (p < 0.05, OR = 0.094; p <0.05, OR = 0.491). TT was a protective factor in rs10814274 of the CREB3 gene (p < 0.05, OR = 0.444). In the RAPGEF4 gene polymorphism rs17746510, TG was the protective genotype, and the TT genotype was a risk factor for clopidogrel resistance. GCG rs5645 was confirmed; there was a relationship between genotypes containing A or G and clopidogrel resistance. CONCLUSION: Single-nucleotide polymorphisms of insulin secretion signaling pathway genes trigger clopidogrel resistance.

The association of polymorphisms in related circadian rhythm genes and clopidogrel resistance susceptibility.

Previous studies have confirmed that a dynamic change in circadian rhythm will affect platelet activity, resulting in clopidogrel resistance (CR). We attempted to evaluate whether polymorphisms of related circadian rhythm genes are involved in CR in stable coronary artery disease (SCAD) patients. A sum of 204 SCAD patients met our requirements and were recruited, and 96 patients were considered to have CR. After clinical data collection and platelet function evaluation, genomic DNA was isolated from human peripheral blood, and 23 tagSNPs from related circadian rhythm genes were genotyped by GenomeLab SNPstream Genotyping System. After RNA isolation, relative expression of related gene mRNAs (CLOCK, CRY1, CACNA1C and PRKCG) was measured by real-time PCR. The results showed that polymorphisms in CRY1, CACNA1C and PRKCG changed the response to clopidogrel. And then, the rs1801260 polymorphism might lead to higher mRNA expression in CLOCK and potentially induce the occurrence of CR. Additionally, the TC genotype of rs3745406 might lower mRNA expression of PRKCG, resulting in CR. These findings support the hypothesized role of circadian rhythm genes in CR and indicate probable biomarkers for CR susceptibility, providing new insight into individualized medicine for coronary heart disease.

Effect of Solution and Aging Temperatures on Microstructure and Mechanical Properties of 10Cr13Co13Mo5Ni3W1VE(S280) Steel.

The article investigated the effects of solution and ging temperatures on microstructure and mechanical properties of ultra-high strength stainless steel 10Cr13Co13Mo5Ni3W1VE(S280). Higher solution temperatures can improve impact toughness because of the quantity reduction of submicron-sized particles which act as microporous nucleation sites. S280 has the best mechanical properties at 1080 °C solution temperature. After quenching, the steel is completely martensite with almost no retained austenite. Aging at 560 °C results in peak strength due to the precipitation of fine carbides coherent zones. The loss of precipitates/matrix coherency and precipitates coarsening cause a decrease in strength at higher aging temperatures. Good strength and toughness obtained at 540 °C aging temperature are attributed to fine and dispersed strengthening phases such as Cr2C and Fe2Mo, and the recovery of austenite in high-density dislocation martensite matrix. The details of electron microscopy research, strengthening and toughening mechanisms are discussed.

[Retracted] MicroRNA­195 inhibits cell proliferation, migration and invasion by targeting defective in cullin neddylation 1 domain containing 1 in cervical cancer.

Following the publication of this paper, it was drawn to the Editors' attention by a concerned reader that certain of the Transwell assay data in the article (featured in Figs. 3B and 7B) were strikingly similar to data appearing in different form in other articles by different authors at different research institutes that had already been published elsewhere at the time of the present article's submission. Furthermore, the scratch wound assay data in Fig. 7A of the above paper were strikingly similar to data published elsewhere. Owing to the fact that the contentious data in the above article had already appeared in different form in other articles prior to its submission to International Journal of Molecular Medicine, the Editor has decided that this paper should be retracted from the Journal. The authors did not reply to indicate whether or not they agreed with the retraction of the paper. The Editor apologizes to the readership for any inconvenience caused. [the original article was published in International Journal of Molecular Medicine 42: 779-788, 2018; DOI: 10.3892/ijmm.2018.3660].

Successful upgrade to cardiac resynchronization therapy for cardiac implantation-associated left subclavian vein occlusion: A case report.

BACKGROUND: Subclavian vein stenosis or occlusion may be caused by a transvenous pacemaker, which makes the reimplantation of a new pacemaker lead difficult. Transvenous pacemaker lead implantation-related subclavian vein occlusion may present difficulty with regard to cardiac resynchronization therapy (CRT) upgrade. CASE SUMMARY: We report the case of a 46-year-old man who was admitted with total subclavian vein occlusion caused by a permanent pacemaker that had been implanted 2 years previously. We successfully treated this patient with an upgrade to a CRT pacemaker by utilizing transferable interventional coronary and radiological techniques. The patient recovered uneventfully during the follow-up period. CONCLUSION: CRT upgrade is still a viable technique for the treatment of subclavian vein obstruction caused by previous pacemaker implantation.

Associations of PER3 polymorphisms with clopidogrel resistance among Chinese Han people treated with clopidogrel.

BACKGROUND: Changes in circadian rhythm are related to various diseases, such as immune system diseases and cardiovascular diseases. The PERIOD3 (PER3) clock gene is one of the most important genes in the rhythm regulation system. Our goal was to evaluate the possible association between the PER3 rs228729 (T/C) polymorphism or PER3 rs2797685(T/C) polymorphism and clopidogrel resistance (CR) and to study the impact of clinical baseline data on clopidogrel resistance. METHODS: PER3 polymorphisms rs2797685 (T/C) and rs228729 (T/C) were assessed in 156 patients with (72) and without (84) CR. Blood samples were collected and analyzed after the application of clopidogrel for interventional therapy. RESULTS: Age, albumin, PLT, and PCT levels influenced the risk of CR (p < 0.05). For rs2797685, when the PCT value was greater than 0.19, patients with the TT + TC genotype had an increased risk of clopidogrel resistance compared with those with the CC genotype (PCT ≥ 0.19, p = 0.014; PCT p = 0.004). In patients with albumin values greater than 40 or PCT greater than 0.19, those with the rs228729 TT + TC genotype had an increased risk of clopidogrel resistance compared with those with the CC genotype (albumin≥40, TT+TC:CC, p = 0.01, albumin p = 0.005; PCT ≥ 0.19, TT+TC:CC, p < 0.001, PCT p = 0.004). Logistic regression analysis of clinical baseline data and genotype showed that high albumin is a protective factor against clopidogrel resistance. The PER3 gene polymorphism has no clear correlation with clopidogrel resistance. CONCLUSION: In summary, our research shows that PER3 SNPs may be helpful to assess the pathogenesis of CR.

Clopidogrel Resistance Is Associated With DNA Methylation of Genes From Whole Blood of Humans.

Antiplatelet therapy has become a cornerstone in the treatment of coronary heart disease (CHD). However, due to high-residual-platelet-reactivity, clopidogrel resistance (CR) is a common phenomenon, and it is rarely known about the relationship between CR and epigenetic changes. This study compared the whole genomic methylation patterns of blood samples from patients with CR (n = 6) and non-CR (n = 6) with the Human Methylation 850K BeadChip assay. We explored differentially methylated CpG sites, genes, and pathways using bioinformatics profiling. The CR and control groups showed significantly different DNA methylation at 7,098 sites, with 979 sites showing hypermethylation and 6,119 sites showing hypomethylation. The pyrosequencing method was used to validate four differentially methylated CpG loci (cg23371584, cg15971518, cg04481923, cg22507406), confirming that DNA methylation was associated with the risk of CR (30 CR vs. 30 non-CR). The relative mRNA expression of the four genes (BTG2, PRG2, VTRNA2-1, PER3) corresponding to the loci above was also associated with CR, suggesting that alterations in DNA methylation may affect the expression of these four genes, eventually resulting in CR. Additionally, differentially methylated sites are partially related to genes and pathways that play key roles in process of circadian entrainment, insulin secretion, and so on. Hence, the mechanism and biological regulation of CR might be reflected through these epigenetic alterations, but future research will need to address the causal relationships.

MicroRNA­195 inhibits cell proliferation, migration and invasion by targeting defective in cullin neddylation 1 domain containing 1 in cervical cancer.

MicroRNAs (miRs), a class of small non­coding RNAs, have been demonstrated to perform promoting or suppressive roles in various types of human malignancy. Deregulation of miR­195 has been observed in numerous types of human cancer, including cervical cancer; however, the detailed molecular mechanism of miR­195 underlying the malignant progression of cervical cancer remains largely unclear. In the present study, miR­195 was significantly downregulated in cervical cancer tissue samples compared with adjacent non­tumor tissue samples, and the reduced expression level of miR­195 was associated with node metastasis and an advanced clinical stage in cervical cancer. Furthermore, the patients with low miR­195 expression levels demonstrated shorter survival times when compared with those with high miR­195 expression levels. In vitro experiments indicated that miR­195 exerted suppressive effects on the proliferation, migration and invasion of cervical cancer cells. Luciferase reporter gene assay identified defective in cullin neddylation 1 domain containing 1 (DCUN1D1) as a novel target gene of miR­195 and the expression level of DCUN1D1 was identified to be negatively regulated by miR­195 in cervical cancer cells. DCUN1D1 was significantly upregulated in cervical cancer, with a negative correlation to miR­195 expression. Furthermore, upregulation of DCUN1D1 was associated with the malignant progression and poor prognosis of cervical cancer. DCUN1D1 overexpression attenuated the suppressive effects of miR­195 on the malignant phenotypes of cervical cancer cells. Notably, the expression levels of miR­195 were significantly lower in HeLa [human papilloma virus (HPV)18+] and SiHa (HPV16+) cells compared with those in C33A (HPV­) cells, and knockdown of E6 using small interfering RNA significantly increased the miR­195 expression while the DCUN1D1 expression level was reduced in HeLa and SiHa cells. Thus, these findings indicate that miR­195 exerts a suppressive role in cervical cancer by targeting DCUN1D1. Therefore, miR­195 may present as a potential therapeutic candidate for cervical cancer.

CDKN2A and CDKN2B methylation in coronary heart disease cases and controls.

The aim of the present study was to investigate the association between cyclin-dependent kinase inhibitor 2A (CDKN2A) and cyclin-dependent kinase inhibitor 2B (CDKN2B) methylation, and coronary heart disease (CHD), and to explore the interaction between methylation status and CHD clinical characteristics in Han Chinese patients. A total of 189 CHD (96 males, 93 females) and 190 well-matched non-CHD controls (96 males, 94 females) were recruited for the study. Methylation-specific polymerase chain reaction technology was used to examine gene promoter methylation status. Comparisons of methylation frequencies between CHD and non-CHD patients were carried out using the Chi-square test. Methylation levels of CDKN2A and CDKN2B genes were not found to be associated with the risk of CHD. However, the mean age of CDKN2A-hypermethylated participants was significantly lower than CDKN2A-unmethylated participants (58.73±5.88 vs. 62.62±5.36 years, adjusted P<0.001). Conversely, the mean age of CDKN2B-hypermethylated participants was significantly higher compared with CDKN2B-unmethylated participants (62.26±5.48 vs. 58.33±7.47 years, adjusted P=0.048). In addition, CDKN2B methylation frequencies were significantly increased in female participants compared with males (99.47 vs. 11.98%, P=0.032). In conclusion, the results indicated that CDKN2A and CDKN2B promoter methylation frequencies were significantly associated with age, and there was a gender dimorphism in CDKN2B methylation.