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OBJECTIVE: To observe the expression and clinical implication of plasma miR-328 in patients with atrial fibrillation (AF). METHODS: Fifty-eight patients with AF (AF group: 17 paroxysmal AF, 21 persistent AF, and 20 permanent AF) and 15 healthy volunteers (Control group) were included. General clinical data and related biochemical parameters were collected. Plasma miR-328 levels were detected with quantitative real-time polymerase chain reaction (qRT-PCR) analysis. The correlation between plasma miR-328 and AF risk factors was analyzed. RESULTS: (1) Compared with the control group, the expression level of plasma miR-328 was significantly elevated in AF group (fold 7.72 ± 9.32) (P < 0.05). (2) In AF group, the expression of plasma miR-328 was significantly different in different type of AF[paroxysmal AF with (1.98 ± 0.81), persistent AF with (6.57 ± 5.82) and permanent AF with (13.47 ± 12.29)] (P < 0.05), and which was increased in proportion to the duration of AF. (3) There was a positive correlation between plasma miR-328 level and left atrial diameter in the AF group (r = 0.310, P < 0.05). CONCLUSION: miR-328 expression is significantly increased in patients with AF, which may be involved in the atrial remodeling process of AF.
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Fibrilação Atrial/sangue , MicroRNAs/sangue , Idoso , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Heart failure (HF) severely impairs human health because of its high incidence and mortality. Cardiac hypertrophy is the main cause of HF, while its underlying mechanism is not fully clear. As an E3 ubiquitin ligase, Ring finger protein 13 (RNF13) plays a crucial role in many disorders, such as liver immune, neurological disease and tumorigenesis, whereas the function of RNF13 in cardiac hypertrophy remains largely unknown. In the present study, we found that the protein expression of RNF13 is up-regulated in the transverse aortic constriction (TAC)-induced murine hypertrophic hearts and phenylephrine (PE)-induced cardiomyocyte hypertrophy. Functional investigations indicated that RNF13 global knockout mice accelerates the degree of TAC-induced cardiac hypertrophy, including cardiomyocyte enlargement, cardiac fibrosis and heart dysfunction. On the contrary, adeno-associated virus 9 (AAV9) mediated-RNF13 overexpression mice alleviated cardiac hypertrophy. Furthermore, we demonstrated that adenoviral RNF13 attenuates the PE-induced cardiomyocyte hypertrophy and down-regulates the expression of cardiac hypertrophic markers, while the opposite results were observed in the RNF13 knockdown group. The RNA-sequence of RNF13 knockout and wild type mice showed that RNF13 deficiency activates oxidative stress after TAC surgery. In terms of the mechanism, we found that RNF13 directly interacted with p62 and promoted the activation of downstream NRF2/HO-1 signaling. Finally, we proved that p62 knockdown can reverse the effect of RNF13 in cardiac hypertrophy. In conclusion, RNF13 protects against the cardiac hypertrophy via p62-NRF2 axis.
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Insuficiência Cardíaca , Fator 2 Relacionado a NF-E2 , Animais , Camundongos , Cardiomegalia/metabolismo , Insuficiência Cardíaca/patologia , Camundongos Endogâmicos C57BL , Camundongos Knockout , Miócitos Cardíacos/metabolismo , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Transdução de Sinais , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismoRESUMO
BACKGROUND: Controversy exists as to the optimal treatment approach for ostial left anterior descending (LAD) or ostial left circumflex artery (LCx) lesions. Drug-coated balloons (DCB) may overcome some of the limitations of drug-eluting stents (DES). Therefore, we investigated the security and feasibility of the DCB policy in patients with ostial LAD or ostial LCx lesions, and compared it with the conventional DES-only strategy. METHODS: We retrospectively enrolled patients with de novo ostial lesions in the LAD or LCx who underwent interventional treatment. They were categorized into two groups based on their treatment approach: the DCB group and the DES group. The treatment strategies in the DCB group involved the use of either DCB-only or hybrid strategies, whereas the DES group utilized crossover or precise stenting techniques. Two-year target lesion revascularization was the primary endpoint, while the rates of major adverse cardiovascular events, cardiac death, target vessel myocardial infarction, and vessel thrombosis were the secondary endpoints. Using propensity score matching, we assembled a cohort with comparable baseline characteristics. To ensure result analysis reliability, we conducted sensitivity analyses, including interaction, and stratified analyses. RESULTS: Among the 397 eligible patients, 6.25% of patients who were planned to undergo DCB underwent DES. A total of 108 patients in each group had comparable propensity scores and were included in the analysis. Two-year target lesion revascularization occurred in 5 patients (4.90%) and 16 patients (16.33%) in the DCB group and the DES group, respectively (odds ratio = 0.264, 95% CI: 0.093-0.752, P = 0.008). Compared with the DES group, the DCB group demonstrated a lower major adverse cardiovascular events rate (7.84% vs. 19.39%, P = 0.017). However, differences with regard to cardiac death, non-periprocedural target vessel myocardial infarction, and definite or probable vessel thrombosis between the groups were non-significant. CONCLUSIONS: The utilization of the DCB approach signifies an innovative and discretionary strategy for managing isolated ostial lesions in the LAD or LCx. Nevertheless, a future randomized trial investigating the feasibility and safety of DCB compared to the DES-only strategy specifically for de novo ostial lesions in the LAD or LCx is highly warranted.
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BACKGROUND: Currently, there is no optimal treatment strategy for ostial left anterior descending (LAD) or ostial left circumflex artery (LCx) lesions. This study explored effectiveness and safety of drug-coated balloons (DCB) in individuals presenting with ostial LAD or LCx lesions. METHODS: A total of 137 patients with de novo ostial LAD or LCx lesions scheduled for DCB treatment were prospectively recruited into the study. After mandatory lesion preparation, DCB-only or hybrid strategy [DCB + drug-eluting stent (DES)] were performed on 120 patients (87.59%). The primary endpoint was the rate of 2-year target lesion revascularization (TLR). Rates of major adverse cardiovascular events (MACE), cardiac death, target vessel myocardial infarction (TVMI), and vessel thrombosis were explored as the secondary outcomes. Quantitative coronary angiography software was used to analyze coronary angiograms. RESULTS: Of the participants, 58 were treated with DCB-only and 62 with hybrid strategy. Relative to the DCB-only group, patients in the hybrid group had longer target lesions (15.47 ± 10.08 vs. 36.85 ± 9.46 mm, P<0.001) and higher Synergy between Percutaneous Coronary Intervention with TAXUS and Cardiac Surgery (SYNTAX) scores (23.47 ± 5.22 vs. 29.98 ± 3.18, P<0.001). During follow-up (731 ± 64 days), neither the primary endpoint (TLR) nor the secondary endpoints (including MACE, cardiac death, TVMI, and vessel thrombosis) differed statistically between the two groups (all P > 0.05). Treatment strategy (DCB-only or hybrid) was not a significant risk factor for TLR. Patients who underwent DCB-only exhibited less late lumen loss compared with the patients who underwent hybrid strategy (-0.26 ± 0.59 vs. 0.42 ± 0.47 mm, P<0.001) at 1-year angiographic follow-up. CONCLUSIONS: With regards to safety and efficacy, the strategy of DCB as a standalone therapy was similar in comparison with the hybrid strategy of DCB + DES for ostial LAD and ostial LCx lesions. This approach might be effective and technically easy in treating ostial LAD and LCx diseases.
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PURPOSE: High-normal blood pressure has been suggested to associate with target organ damage and higher left ventricular mass index (LVMI). Our aim is to find the association between people with high-normal blood pressure and their left ventricular mass index. MATERIALS AND METHODS: Given a total of 181 people with office blood pressure, 24-hour ambulatory blood pressure monitoring, 35 of them are normotensive (BP < 130/85 mm Hg), and 146 people with high-normal blood pressure (BP 130-139/85-89 mm Hg), divide the high-normal blood pressure group into dipper and nondipper according to their ABPM in 24 hours. All of them were performed with echocardiography to calculate LVMI. RESULTS: After adjusting for potential confounding factors, mean systolic blood pressure (BP) of the nondipper group is (119 + 9) mmHg in 24 h, which is significantly higher (p < 0.05) than in the dipper group (116 + 11) mmHg, indicating the mean systolic BP is associated with the dipper type (p < 0.05); furthermore, the higher nocturnal blood pressure is associated with the nondipper group significantly (p < 0.05), and LVMI ((121 ± 11) g/m2) of the nondipper group is also significantly higher than in the dipper group's LVMI ((108 ± 12) g/m2) (p < 0.05). The multivariate linear regression analyses revealed significant and independent associations of LVMI with these factors: triglyceride (TG), total cholesterol (TC), low-density lipoprotein (LDL-C), and coefficient of variation of systolic and diastolic blood pressure in 24 hours. CONCLUSION: After multiple relevant clinical confounding factors were adjusted, patients with dipper and nondipper high-normal blood pressure had higher LVMI. Abnormalities in circadian blood pressure variability may be associated with the left ventricular hypertrophy.
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Pathological myocardial hypertrophy is regulated by multiple pathways. However, its underlying pathogenesis has not been fully explored. The goal of this work was to elucidate the function of polypeptide N-acetylgalactosaminyltransferase 4 (GALNT4) in myocardial hypertrophy and its underlying mechanism of action. We illustrated that GALNT4 was upregulated in the models of hypertrophy. Two cardiac hypertrophy models were established through partial transection of the aorta in GALNT4-knockout (GALNT4-KO) mice and adeno-associated virus 9-GALNT4 (AAV9-GALNT4) mice. The GALNT4-KO mice demonstrated accelerated cardiac hypertrophy, dysfunction, and fibrosis, whereas the opposite phenotype was observed in AAV9-GALNT4 mice. Similarly, GALNT4 overexpression mitigated the degree of phenylephrine-induced cardiomyocyte hypertrophy in vitro whereas GALNT4 knockdown aggravated the hypertrophy. In terms of mechanism, GALNT4 deficiency increased the phosphorylation and activation of ASK1 and its downstream targets (JNK and p38), whereas GALNT4 overexpression inhibited activation of the ASK1 pathway. Furthermore, we demonstrated that GALNT4 can directly bind to ASK1 inhibiting its N-terminally mediated dimerization and the subsequent phosphorylation of ASK1. Finally, an ASK1 inhibitor (iASK1) was able to reverse the effects of GALNT4 in vitro. In summary, GALNT4 may serve as a new regulatory factor and therapeutic target by blocking the activation of the ASK1 signaling cascade.
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Cardiomegalia/genética , N-Acetilgalactosaminiltransferases/metabolismo , Domínios e Motivos de Interação entre Proteínas/genética , Animais , Modelos Animais de Doenças , Humanos , Masculino , Camundongos , Transdução de Sinais , Polipeptídeo N-AcetilgalactosaminiltransferaseRESUMO
OBJECTIVE: To screen the mutations of RET proto-oncogene in sporadic patients with pheochromocytoma. METHODS: Forty-two cases of sporadic pheochromocytoma were tested for mutations of RET gene. Of these 42 DNA samples, 12 were extracted from peripheral blood cells and 30 from paraffin-embedded pheochromocytoma specimens. The PCR product of exon 10 and exon 11 was used to molecular analysis of the RET proto-oncogene. RESULTS: Among 42 patients, 2 were found to have RET gene mutations. One of mutations located at codon 634 (TGC>TAC) in exon 11 of RET proto-oncogene. Another one located at codon 632 (GAG>AAG). CONCLUSION: Some patients with apparently sporadic pheochromacytoma were carrier of mutations, a routine genetic analysis for mutations of RET gene is indicated for these patients.
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Neoplasias das Glândulas Suprarrenais/genética , Mutação , Feocromocitoma/genética , Proteínas Proto-Oncogênicas c-ret/genética , Neoplasias das Glândulas Suprarrenais/diagnóstico , Adulto , Povo Asiático/genética , Sequência de Bases , China , Análise Mutacional de DNA , Feminino , Predisposição Genética para Doença/genética , Testes Genéticos , Humanos , Masculino , Pessoa de Meia-Idade , Feocromocitoma/diagnóstico , Reação em Cadeia da Polimerase , Proto-Oncogene MasRESUMO
Mitochondrial DNA (MtDNA) mutations played an important role in the development of essential hypertension. Mitochondrial tRNA point mutations, caused the failure in tRNA metabolism, responsible for the pathogenesis of this complex disease. In this study, we evaluated the possible role of the 4329C >G mutation in the clinical expression of hypertension in a Chinese family. Analysis of the complete mtDNA sequence variants showed that other mutations may play synergic roles in the phenotypic manifestation of hypertension. In addition, other potential pitfalls were also discussed in this context.
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Povo Asiático/genética , DNA Mitocondrial/genética , Hipertensão Essencial/genética , Mutação/genética , Sequência de Bases , Família , Humanos , RNA de Transferência/genética , Alinhamento de SequênciaRESUMO
The Box-Jenkins approach was used to fit an autoregressive integrated moving average (ARIMA) model to the incidence of hemorrhagic fever with renal Syndrome (HFRS) in China during 1986-2009. The ARIMA (0, 1, 1) × (2, 1, 0)(12) models fitted exactly with the number of cases during January 1986-December 2009. The fitted model was then used to predict HFRS incidence during 2010, and the number of cases during January-December 2010 fell within the model's confidence interval for the predicted number of cases in 2010. This finding suggests that the ARIMA model fits the fluctuations in HFRS frequency and it can be used for future forecasting when applied to HFRS prevention and control.
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Febre Hemorrágica com Síndrome Renal/epidemiologia , Modelos Estatísticos , China/epidemiologia , Previsões , Humanos , Incidência , Estações do AnoRESUMO
OBJECTIVE: To know the genotype and subtype of hantavirus (HV) carried by host animals in HFRS natural epidemic area of Hebei province. METHODS: According to the conservative sequence of 76-118 and R22 strains, specific primers were designed. RT-nested PCR was used to amplify partial M segments from the positive rat lungs screened by IFA. Agarose gel electrophoresis was used to identify the types. Nucleotides were assayed from partial products after purification and reclaim. Gene analysis was carried on with DNAStar package. RESULTS: 32 specimens, which were positive screened by IFA, were amplified the specific segment (418bp) and all belonged to type SEO. Sequencing results of 10 partial segments indicated that G2 segment had little variability and nucleotide homology reached to 98.0%-100.0%. Comparing with the R22 and 76-118 strains, homology was 93.3%-94.3% and 67.7%-69.0% respectively. CONCLUSION: According to G2 segment, SEO was the major type in Hebei HFRS natural epidemic area and S3 was the major subtype. HV which belonged to the same subtype had high homology and genetic materials were correspondingly stable. Different rats could carry the same subtype of HV.
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Reservatórios de Doenças/virologia , Orthohantavírus/genética , RNA Viral/genética , Ratos/virologia , Animais , Animais Selvagens/virologia , Genótipo , Orthohantavírus/classificação , Orthohantavírus/isolamento & purificação , Pulmão/virologia , Dados de Sequência Molecular , Filogenia , Análise de Sequência de DNARESUMO
OBJECTIVE: To know the genotype and subtype of hantavirus (HV) which infected persons in Hebei province. METHODS: According to G2 coding region of 76-118 and R22 strains, specific type primers were designed to detect and identity the types of HV in HFRS patients' sera with RT-nested PCR. Nucleotides were assayed from partial products after purification and reclaim. Then, gene analysis was done with DNAStar package. RESULTS: 17 out of 69 positive serum specimens were successfully detected by RT-PCR and the detection rate was 24.64%, among which,