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Using Origin2022Pro, PAST4.09, GraphPad, and ArcGIS, this study analyzed the big data of the fourth national survey of traditional Chinese medicine resources in Jilin province from five dimensions: differences in resource quantity, taxonomic group, family, and genus, regional distribution, and spatiotemporal distribution, aiming to fully elucidate the biodiversity of medicinal plants in Jilin province. The results indicated that 2 241 species of medicinal plants existed in Jilin province, belonging to 881 genera of 243 families, with 20 dominant families and 3 dominant genera. There were 1 901 species of medicinal plants(belonging to 778 genera of 227 families) in the eastern mountainous region, 1 503 species(belonging to 690 genera of 225 families) in the mid-mountainous areas of the central mountainous region, and 811 species(belonging to 436 genera of 136 families) in the western plain region. The biodiversity of medicinal plants in Jilin province was high and presented a trend of high in the east and low in the west. The medicinal plant resources were mainly concentrated in the eastern mountainous region, and the number of medicinal plant groups had significant diffe-rences between regions, following the trend of western region > central region > eastern region. The species richness was in the order of eastern region > western region > central region. The species diversity structure in the central region was similar to that in the eastern and western regions, while it was significantly different between the western and eastern regions. Compared with the third national survey of traditional Chinese medicine resources, the fourth survey showed an increase of 1 417 species, a decrease of 580 species, and 824 common species, indicating significant changes in the biodiversity of medicinal plants in Jilin province. The reasons for these changes need to be further explored. This article elucidates the background and biodiversity changes of medicinal plant resources in Jilin province, laying a foundation for the protection, utilization, and industrial development of traditional Chinese medicine resources in Jilin province.

Asunto(s)

Biodiversidad , Medicina Tradicional China , Plantas Medicinales , Plantas Medicinales/química , Plantas Medicinales/clasificación , Plantas Medicinales/crecimiento & desarrollo , China , Encuestas y Cuestionarios

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INTRODUCTION: Tegoprazan (TPZ), a potassium-competitive acid blocker, exerts a strong acid-suppression effect and a rapid onset of action. However, research on TPZ-amoxicillin (TA) dual treatment is limited. Here, we compared the safety and efficacy of TPZ-amoxicillin dual treatment and TPZ, bismuth potassium citrate, amoxicillin, and clarithromycin (TBAC) quadruple therapy in patients newly diagnosed with H. pylori infection over a 14-day treatment period. METHODS: A total of 236 patients newly diagnosed with H. pylori were enrolled in this multicenter, prospective, open-label, and randomized controlled study. Patients randomly received either TA dual or TBAC quadruple therapy. The incidence of adverse reactions and treatment compliance were recorded and then analyzed. RESULTS: The intention-to-treat analysis revealed that H. pylori eradication rates were 83.9% (95% confidence interval 78.2%-91.3%) and 81.4% (95% confidence interval 74.2%-88.5%) for the TA and TBAC groups, respectively, with no statistically significant difference between them ( P = 0.606). The per-protocol analysis revealed that the H. pylori eradication rates were 88.3% and 84.8% for the TA and TBAC groups, respectively ( P = 0.447). The incidence of adverse reactions was significantly lower in the TA group than in the TBAC group (4.2% vs 15.3%, P = 0.004). Moreover, the TA group demonstrated substantially higher treatment compliance than the TBAC group (94.1% vs 89.0%, P = 0.020). DISCUSSION: The TA dual therapy successfully eradicated H. pylori with a high eradication rate and a low incidence of adverse reactions. Therefore, this treatment is recommended as an alternative course for patients newly diagnosed with H. pylori infection.

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BACKGROUND: According to the Maastricht VI/Florence consensus report, potassium-competitive acid blockers (P-CAB) may improve Helicobacter pylori eradication treatment. MATERIALS AND METHODS: A total of 213 H. pylori treatment-naive patients aged between 18 and 70 years were treated with two regimens. The two regimens are VDT: 20 mg vonoprazan twice a day and 1 g amoxicillin three times daily and EDT: 20 mg esomeprazole four times a day and 750 mg amoxicillin four times daily. 13 C-urea breath tests were used to evaluate eradication rate 4-6 weeks after treatment. Based on propensity score matching (PSM), this retrospective study analyzed the eradication rates, adverse events (AEs), compliance, and antibiotic resistance rates in VDT and EDT groups. RESULTS: On intention-to-treat (ITT) analysis, the eradication rate in VDT group (89.0%; 95% CI 81.7-96.3) was non-inferior to that in EDT group (87.7%; 95% CI 80.1-95.3; p = 0.796). The corresponding per-protocol (PP) eradication rates were 94.1% (95% CI 88.4-99.8) and 92.8% (95% CI 86.7-98.9; p = 1.000), respectively. There were no significant between-group differences with respect to compliance or incidence of AEs. CONCLUSIONS: The efficacy and safety of 14-day VDT and EDT were comparable. Therefore, 14-day VDT or EDT may be recommended for the first-line treatment of H. pylori infection.

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Infecciones por Helicobacter , Helicobacter pylori , Humanos , Adolescente , Adulto Joven , Adulto , Persona de Mediana Edad , Anciano , Infecciones por Helicobacter/tratamiento farmacológico , Esomeprazol/uso terapéutico , Antibacterianos/efectos adversos , Estudios Retrospectivos , Puntaje de Propensión , Inhibidores de la Bomba de Protones/efectos adversos , Amoxicilina/uso terapéutico , Quimioterapia Combinada , Resultado del Tratamiento , Claritromicina/uso terapéutico

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BACKGROUND: Patients who undergo coronary artery bypass grafting (CABG) are known to be at a significant risk of experiencing long-term adverse events, emphasizing the importance of regular assessments. Evaluating health-related quality of life (HRQoL) serves as a direct method to gauge prognosis. Our objective is to ascertain the prognostic significance of consecutive HRQoL assessments using the Physical Component Summary (PCS) and Mental Component Summary (MCS) derived from the Short-Form 36 (SF-36) health survey in CABG patients. METHODS: The study population consisted of 433 patients who underwent isolated elective CABG at Fuwai Hospital between 2012 and 2013. SF-36 assessments were conducted during both the hospitalization period and follow-up. The primary endpoint of the study was all-cause mortality, while the secondary outcome was a composite measure including death, myocardial infarction, stroke, and repeat revascularization. We assessed the relationships between the PCS and MCS at baseline, as well as their changes during the first 6 months after the surgery (referred to as ΔPCS and ΔMCS, respectively), and the observed outcomes. RESULTS: The patients were followed for an average of 6.28 years, during which 35 individuals (35/433, 8.1%) died. After adjusting for clinical variables, it was observed that baseline MCS scores (hazard ratio [HR] for a 1-standard deviation [SD] decrease, 1.57; 95% confidence interval [CI], 1.07-2.30) and ΔMCS (HR for a 1-SD decrease, 1.67; 95% CI, 1.09-2.56) were associated with all-cause mortality. However, baseline PCS scores and ΔPCS did not exhibit a significant relationship with all-cause mortality. Notably, there was a dose-response relationship observed between ΔMCS and the likelihood of all-cause mortality (HRs for the 2nd, 3rd and 4th quartiles compared to the 1st quartile, 0.33, 0.45 and 0.11, respectively). CONCLUSIONS: Baseline MCS and changes in MCS were independent predictors for long-term mortality of CABG. Better mental health status and recovery indicated better prognosis.

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Although N-terminal pro-B-type natriuretic peptide (NT-proBNP) has been validated as a cardiovascular biomarker, its ability to predict long-term outcomes after coronary artery bypass grafting (CABG) has not been fully explored. We aimed to assess the prognostic value of NT-proBNP beyond clinical risk prediction tools, and its relevance to follow-up events and interactions with different treatment selections. The study included 11,987 patients who underwent CABG who underwent surgery between 2014 and 2018. The primary end point was all-cause mortality during follow-up, whereas the secondary end points included cardiac death and major adverse cardiac and cerebrovascular events, which comprised death, myocardial infarction, and ischemic cerebrovascular accident. We evaluated the associations between NT-proBNP levels and outcome and the added prognostic value of NT-proBNP to clinical tools. Patients were followed up for a median of 4.0 years. Higher preoperative NT-proBNP levels were significantly associated with all-cause mortality, cardiac death, and major adverse cardiac and cerebrovascular events (all p <0.001). These associations remained significant after the full adjustment. Integration of NT-proBNP into clinical tools significantly improved the prediction accuracy for all end points. We also found that patients with higher preoperative NT-proBNP levels benefited more from ß blockers (p for interaction = 0.045). In conclusion, we demonstrated the prognostic value of NT-proBNP in risk stratification and personalized treatment decisions in patients who underwent CABG.

Asunto(s)

Puente de Arteria Coronaria , Péptido Natriurético Encefálico , Humanos , Pronóstico , Biomarcadores , Fragmentos de Péptidos

RESUMEN

A TiTaNbZrHf refractory high-entropy alloy (RHEA) was synthesized through a cold isostatic pressing and a pressure-less sintering process in a hydrogen atmosphere using a powder mixture of metal hydride prepared either by mechanical alloying (MA) or by rotating mixing. This study investigates how differences in powder particle sizes impact the RHEA's microstructure and mechanical properties. HCP (a = b = 3.198 Å, c = 5.061 Å) and BCC2 (a = b = c = 3.40 Å) phases were observed in the microstructure of coarse powder TiTaNbZrHf RHEAs at 1400 °C. In contrast, fine powder RHEAs were found to possess two-phase structures of HCP and BCC1 (a = b = c = 3.36 Å) with a higher hardness of 431 HV, compression strength of 1620 MPa, and a plasticity of >20%.

RESUMEN

Based on high-throughput transcriptomic sequencing, SNHG3 was among the most highly expressed long noncoding RNAs in calcific aortic valve disease. SNHG3 upregulation was verified in human and mouse calcified aortic valves. Moreover, in vivo and in vitro studies showed SNHG3 silencing markedly ameliorated aortic valve calcification. In-depth functional assays showed SNHG3 physically interacted with polycomb repressive complex 2 to suppress the H3K27 trimethylation BMP2 locus, which in turn activated BMP2 expression and signaling pathways. Taken together, SNHG3 promoted aortic valve calcification by upregulating BMP2, which might be a novel therapeutic target in human calcific aortic valve disease.

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BACKGROUND: Guidelines on the diagnosis and management of hypertrophic cardiomyopathy (HCM) recommend that septal myectomy be performed by experienced operators. However, the impact of operator volume on surgical treatment outcomes for isolated HCM has been poorly investigated. METHODS: From 2002 to 2014, 435 consecutive patients with isolated HCM undergoing myectomy at the Fuwai Hospital were retrospectively enrolled. All 29 surgeons were divided into beginner surgeons (operator volume ≤20) and experienced surgeons (operator volume >20) according to the guidelines for the diagnosis and treatment of HCM. Propensity score matching of patients in the two groups was performed. RESULTS: Baseline differences included advanced New York Heart Association classification and older age in the experienced surgeon group. After matching, in the beginner surgeon group (107 cases), residual obstruction (18.7% vs. 0.9%, P<0.001) was more common, and the postoperative left ventricular outflow tract pressure gradient (20.7±15.1 vs. 14.3±7.4 mmHg, P<0.001) was higher than that of the experienced surgeon group. In the experienced surgeon group (107 cases), the incidence of mitral valve replacement (1.9% vs. 11.2%, P<0.001) and permanent pacemaker implantation (1.9% vs. 3.7%, P<0.001) was significantly lower than that in the beginner surgeon group. However, there was no difference in procedural mortality (1.9% vs. 1.9%) between the two groups. CONCLUSIONS: Operator volume is an important factor in achieving better obstruction obliteration after septal myectomy in patients with isolated HCM.

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BACKGROUND: Secondary preventive therapies play a key role in the prevention of adverse events after coronary artery bypass grafting (CABG). However, adherence to secondary preventive drugs after CABG is often poor. With the increasing penetration of smartphones, health-related smartphone applications might provide an opportunity to improve medication adherence. We aimed to evaluate the effectiveness and feasibility of using a smartphone-based application to improve medication adherence in patients after CABG. METHODS: The Measurement and Improvement Studies of Surgical coronary revascularizatION: medication adherence (MISSION-2) study is a multicenter randomized controlled trial that planned to enroll over 1000 patients who underwent isolated CABG at one of four large teaching hospitals in China; all enrolled participants had access to a smartphone and were able to operate at least three smartphone applications. The investigators randomly assigned the participants to one of two groups: (1) the intervention group with an advanced smartphone application for 6 months which was designed specifically for this trial and did not exist before. Participants could receive medication reminders and cardiac health education by the smartphone application or (2) the control group with usual care. The primary outcome was CABG secondary preventive medication adherence as measured by the translated Chinese version of the 8-item Morisky Medication Adherence Scale (MMAS-8) at 6 months after randomization. The secondary outcomes were mortality, major adverse cardiovascular and cerebrovascular events (MACCE), cardiovascular rehospitalization, self-reported secondary preventive medication use after 6 months of follow-up, blood pressure (BP), body mass index (BMI), and self-reported smoking status. All analyses were conducted using the intention-to-treat principle. RESULTS: A total of 1000 patients (mean age, 57.28 [SD, 9.09] years; 85.5% male) with coronary heart disease after CABG were enrolled between September 2015 and September 2016 and were randomly assigned to the intervention (n = 501) or control group (n = 499). At 6 months, the proportion of low-adherence participants, categorized by MMAS-8 scores, was 11.8% in the intervention group and 11.7% in the control group (RR = 1.005, 95% CI 0.682 to 1.480, P = 1.000). Similar results were found in sensitivity analyses that considered participants who withdrew from the study, or were lost to follow-up as nonadherent. There were no significant differences in the secondary clinical outcome measures, and there were no significant differences in the primary outcome across the subgroups tested. In the intervention group, the proportion of participants who used and operated the application during the first month after CABG was 88.1%; however, the use rate decreased sharply from 42.5% in the second month to 9.2% by the end of the study (6 months). CONCLUSIONS: A smartphone-based application supporting secondary prevention among patients after CABG did not lead to a greater adherence to secondary preventive medications. The limited room for improvement in medication adherence and the low participants' engagement with the smartphone applications might account for these non-significant outcomes.

Asunto(s)

Fármacos Cardiovasculares/uso terapéutico , Puente de Arteria Coronaria/efectos adversos , Enfermedad Coronaria , Educación en Salud/métodos , Cumplimiento de la Medicación/estadística & datos numéricos , Complicaciones Posoperatorias , Teléfono Inteligente , Programas Informáticos , Puente de Arteria Coronaria/métodos , Enfermedad Coronaria/tratamiento farmacológico , Enfermedad Coronaria/psicología , Enfermedad Coronaria/cirugía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Evaluación de Resultado en la Atención de Salud , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/prevención & control , Sistemas Recordatorios/instrumentación , Prevención Secundaria/métodos

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AIMS: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) directly binds to ACE2 (angiotensin-converting enzyme 2) to facilitate cellular entry. Compared with the lung or respiratory tract, the human heart exhibits greater ACE2 expression. However, little substantial damage was found in the heart tissue, and no viral particles were observed in the cardiac myocytes. This study aims to analyse ACE2 and SARS-CoV-2 spike (S) protein proteases at the single-cell level, to explore the cardiac involvement in COVID-19 and improve our understanding of the potential cardiovascular implications of COVID-19. METHODS AND RESULTS: With meta-analysis, the prevalence of cardiac injury in COVID-19 patients varies from 2% [95% confidence interval (CI) 0-5%, I2 = 0%] in non-ICU patients to 59% (95% CI 48-71%, I2 = 85%) in non-survivors. With public single-cell sequence data analysis, ACE2 expression in the adult human heart is higher than that in the lung (adjusted P < 0.0001). Inversely, the most important S protein cleavage protease TMPRSS2 (transmembrane protease serine protease-2) in the heart exhibits an extremely lower expression than that in the lung (adjusted P < 0.0001), which may restrict entry of SARS-CoV-2 into cardiac cells. Furthermore, we discovered that other S protein proteases, CTSL (cathepsin L) and FURIN (furin, paired basic amino acid cleaving enzyme), were expressed in the adult heart at a similar level to that in the lung, which may compensate for TMPRSS2, mediating cardiac involvement in COVID-19. CONCLUSION: Compared with the lung, ACE2 is relatively more highly expressed in the human heart, while the key S protein priming protease, TMPRSS2, is rarely expressed. The low percentage of ACE2+/TMPRSS2+ cells reduced heart vulnerability to SARS-CoV-2 to some degree. CTSL and FURIN may compensate for S protein priming to mediate SARS-CoV-2 infection of the heart.

Asunto(s)

Betacoronavirus/patogenicidad , Infecciones por Coronavirus/metabolismo , Miocardio/enzimología , Peptidil-Dipeptidasa A/metabolismo , Neumonía Viral/metabolismo , Análisis de la Célula Individual , Glicoproteína de la Espiga del Coronavirus/metabolismo , Enzima Convertidora de Angiotensina 2 , COVID-19 , Humanos , Pulmón/metabolismo , Pulmón/virología , Pandemias , Péptido Hidrolasas/metabolismo , Proteolisis , SARS-CoV-2

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BACKGROUND: The anatomy of the aortic valves plays an important role in the progression of aortic valve disease (AVD) and determination of the appropriate treatment strategy. We described and compared AVD phenotypes according to detailed anatomical classifications and assessed the accuracy of imaging diagnostics using surgical diagnosis as the gold standard. METHODS AND RESULTS: The study enrolled 602 patients (mean age 55.5±12.9 years; 74.1% male) who underwent their first aortic valve replacement surgery between June 2017 and March 2018 at Fuwai Hospital in Beijing, China. Clinical characteristics, histopathological diagnoses, preoperative transthoracic echocardiography (TTE), and other available imaging data were collected retrospectively from medical records. During surgery, 370 patients were diagnosed with a tricuspid aortic valve (TAV), 228 with a bicuspid aortic valve (BAV), and 4 with a quadricuspid aortic valve (QAV). The primary histopathological finding was myxomatous degeneration (48.4%) for those with TAV and fibrocalcification (57.9%) for those with BAV. Nearly all TAV patients (96.2%) had aortic regurgitation, while the majority of BAV patients had aortic stenosis (73.7%); the severity of stenosis and regurgitation varied across the subtypes of BAV. The overall diagnostic accuracy of preoperative TTE for aortic valve anatomy was 85.5%; accuracy was higher for TAV versus BAV (96.8% vs. 68.0%, P<.001). CONCLUSIONS: We identified different phenotypes of AVD among patients with different detailed anatomical classifications. In addition, the diagnostic accuracy of preoperative TTE for BAV was suboptimal, and more attention is needed to ensure an accurate anatomic diagnosis prior to surgical intervention.

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Válvula Aórtica/anomalías , Válvula Aórtica/cirugía , Enfermedades de las Válvulas Cardíacas/patología , Enfermedades de las Válvulas Cardíacas/cirugía , Implantación de Prótesis de Válvulas Cardíacas , Adulto , Anciano , Válvula Aórtica/diagnóstico por imagen , Insuficiencia de la Válvula Aórtica/patología , Insuficiencia de la Válvula Aórtica/cirugía , Estenosis de la Válvula Aórtica/patología , Estenosis de la Válvula Aórtica/cirugía , Beijing , Enfermedad de la Válvula Aórtica Bicúspide , Femenino , Enfermedades de las Válvulas Cardíacas/diagnóstico por imagen , Humanos , Masculino , Persona de Mediana Edad , Fenotipo , Estudios Retrospectivos , Índice de Severidad de la Enfermedad

RESUMEN

AIM: Calcific aortic valve disease (CAVD) is the most common valvular disease worldwide. The osteoblastic transdifferentiation of aortic valve interstitial cells (VICs) is the essential process of CAVD, but the underlying mechanisms are poorly understood. Aortic VICs are generated from epithelial-to-mesenchymal transition (EMT) and migration of neural crest cells (NCCs).Meis2 has been associated with EMT and NCCs migration during development, but its role in CAVD is unknown. This study aims to elucidate the specific functions of Meis2 and its downstream targets in aortic valve calcification. MATERIAL AND METHODS: Levels of Meis2 were examined in calcified (n = 30) and normal (n = 30) human aortic valve tissues, respectively. Meis2 was inhibited in porcine aortic VICs in vitro, and the effect on osteoblastic transdifferentiation and its downstream pathway were studied. RESULTS: Meis2 gene and protein expression decreased significantly in calcified human aortic valve tissue compared with the normal ones. Inhibiting Meis2 by siRNAs reduced the gene and protein expression of Notch1 and Twist1, and induced the osteoblastic transdifferentiation of the porcine aortic VICs in vitro. CONCLUSIONS: The present study indicated that Meis2 repress the osteoblastic transdifferentiation of aortic VICs through the Notch1/Twist1 signaling pathway. The Results identify Meis2 as a potential intervention target for the prevention of CAVD.

Asunto(s)

Estenosis de la Válvula Aórtica/patología , Válvula Aórtica/patología , Calcinosis/patología , Transdiferenciación Celular , Proteínas de Homeodominio/metabolismo , Osteoblastos/patología , Transducción de Señal , Factores de Transcripción/metabolismo , Anciano , Válvula Aórtica/citología , Válvula Aórtica/metabolismo , Estenosis de la Válvula Aórtica/genética , Estenosis de la Válvula Aórtica/metabolismo , Calcinosis/genética , Calcinosis/metabolismo , Transición Epitelial-Mesenquimal , Femenino , Regulación de la Expresión Génica , Proteínas de Homeodominio/genética , Humanos , Masculino , Persona de Mediana Edad , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Osteoblastos/citología , Osteoblastos/metabolismo , Interferencia de ARN , ARN Interferente Pequeño/genética , Receptor Notch1/genética , Receptor Notch1/metabolismo , Factores de Transcripción/genética , Proteína 1 Relacionada con Twist/genética , Proteína 1 Relacionada con Twist/metabolismo

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OBJECTIVE: As a marker of in vivo thromboxane generation, high-level urinary thromboxane metabolites (TXA-M) increase the occurrence of cardiovascular events in high-risk patients. To investigate whether perioperative urinary TXA-M level is associated with major adverse cardiac and cerebrovascular events (MACCE) after coronary artery bypass graft (CABG) surgery, we designed a nested case-control study. DESIGN: Observational, nested case-control study. SETTING: Single-centre outcomes research in Fuwai Hospital, Beijing, China. PARTICIPANTS: One thousand six hundred and seventy Chinese patients undergoing CABG surgery from September 2011 to October 2013. METHODS: We obtained urinary samples from 1670 Chinese patients undergoing CABG 1 hour before surgery (pre-CABG), and 6 hours (post-CABG 6 hours) and 24 hours after surgery (post-CABG 24 hours). Patients were followed up for 1 year, and we observed 56 patients had MACCE. For each patient with MACCE, we matched three control subjects. Perioperative urinary TXA-M of the three time spots was detected in these 224 patients. RESULTS: Post-CABG 24 hours TXA-M is significantly higher than that of patients without MACCE (11 101vs8849 pg/mg creatine, P=0.007). In addition, patients in the intermediate tertile and upper tertile of post-CABG 24 hours urinary TXA-M have a 2.2 times higher (HR 2.22, 95% CI 1.04 to 4.71, P=0.038) and a 2.8 times higher (HR 2.81, 95% CI 1.35 to 5.85, P=0.006) risk of 1 year MACCE than those in the lower tertile, respectively. CONCLUSIONS: In conclusion, post-CABG 24 hours urinary TXA-M elevation is associated with an increase of 1 year adverse events after CABG, indicating that the induction of cyclo-oxygenase-2 by surgery-related inflammatory stimuli or platelet turnover may be responsible for the high levels of post-CABG urinary TXA-M. TRIAL REGISTRATION NUMBER: NCT01573143.

Asunto(s)

Puente de Arteria Coronaria , Periodo Perioperatorio , Tromboxanos/orina , Enfermedades Cardiovasculares/etiología , Estudios de Casos y Controles , Trastornos Cerebrovasculares/etiología , Puente de Arteria Coronaria/efectos adversos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/orina , Factores de Riesgo , Tromboxanos/metabolismo

RESUMEN

BACKGROUND: Secondary preventive therapies play a key role in the prevention of adverse outcomes after coronary artery bypass grafting (CABG). However, medication adherence after CABG is often poor, and conventional interventions for improving adherence have limited success. With increasing penetration of smartphones, health-related smartphone applications might provide an opportunity to improve adherence. Carefully designed trials are needed to provide reliable evidence for the use of these applications in patients after CABG. METHODS: The Measurement and Improvement Studies of Surgical Coronary Revascularization: Medication Adherence (MISSION-2) study is a multicenter randomized controlled trial, aiming to randomize 1000 CABG patients to the intervention or control groups in a 1:1 ratio. We developed the multifaceted, patient-centered, smartphone-based Heart Health Application to encourage medication adherence in the intervention group through a health self-management program initiated during hospital admission for CABG. The application integrated daily scheduled reminders to take the discharge medications, cardiac educational materials, a dynamic dashboard to review cardiovascular risk factors and secondary prevention targets, and weekly questionnaires with interactive feedback. The primary outcome was secondary preventive medication adherence measured by the Chinese version of the 8-item Morisky Medication Adherence Scale at 6 months after randomization. Secondary outcomes included all-cause death, cardiovascular rehospitalization, and a composite of death, myocardial infarction, stroke, and repeat revascularization. DISCUSSION: Findings will not only provide evidence regarding the feasibility and effectiveness of the described intervention for improving adherence to CABG secondary preventive therapies but also explore a model for outpatient health self-management that could be translated to various chronic diseases and widely disseminated across resource-limited settings. TRIAL REGISTRATION: https://clinicaltrials.gov (NCT02432469).

Asunto(s)

Puente de Arteria Coronaria/métodos , Cumplimiento de la Medicación , Teléfono Inteligente , Humanos , Infarto del Miocardio/prevención & control , Prevención Secundaria/métodos , Accidente Cerebrovascular/prevención & control

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Coronary artery disease (CAD) is the leading cause of mortality and morbidity worldwide. Left main coronary artery disease (LMCAD) is a severe phenotype of CAD and has a genetic component. Previous studies identified 3 inflammation-related single nucleotide polymorphisms (SNPs) contributing to the development of LMCAD. We integrated these SNPs into a genetic risk score for the prediction of LMCAD. We enrolled 1544 patients with CAD between 2007 and 2011. The individual associations of the 3 SNPs with LMCAD were assessed. We then calculated the genetic risk score for each patient and stratified patients into low-risk, intermediate-risk, and high-risk categories of genetic risk. In univariable logistic regression analysis, the odds of LMCAD for the high-risk group were 2.81 (95% confidence interval [CI]: 1.72-4.60; P = 0.02) times those of the low-risk group. After adjustment for CAD-related clinical variables, the high-risk group (adjusted OR: 2.78; 95% CI: 1.69-4.58; P = 0.02) had increased odds of LMCAD when compared with the low-risk group. Comparison of model c-statistics showed greater predictive value with regard to LMCAD for the genetic risk score model than the models including single SNPs.

Asunto(s)

Enfermedad de la Arteria Coronaria/genética , Predisposición Genética a la Enfermedad/genética , Polimorfismo de Nucleótido Simple/genética , Vasos Coronarios/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Factores de Riesgo

RESUMEN

As a particular severe phenotype of coronary artery disease (CAD), left main coronary artery disease (LMCAD) is heritable. Genetic variants related to prostaglandin metabolism are associated with LMCAD. Cyclooxygenase-2 (COX-2), a key synthase in prostaglandin pathways, displays high density in atherosclerotic lesions and promotes early atherosclerosis in CAD progression. We hypothesized that genetic variants in COX-2 gene contribute to LMCAD phenotype susceptibility compared to more peripheral coronary artery disease (MPCAD). In this study, we genotyped COX-2 rs5275, rs5277, and rs689466 of 1544 CAD patients undergoing coronary artery bypass grafting (CABG) and found that rs5277 C allele carriage was associated with LMCAD (adjusted OR: 1.590; 95% CI: 1.103~2.291; p = 0.013). Furtherly, long-term follow-up data suggested that rs5277 C allele carriage increased risk of major adverse cardiac and cerebrovascular events (MACCE) in the whole cohort (adjusted HR: 1.561; 95% CI: 1.025~2.377; p = 0.038) and LMCAD subgroup (adjusted HR: 2.014; 95% CI: 1.036~3.913; p = 0.039) but not in MPCAD subgroup (adjusted HR: 1.375; 95% CI: 0.791~2.392; p = 0.259). In conclusion, we demonstrate that COX-2 rs5277 C allele increases the risk of left main coronary artery lesion and is also correlated with poor prognosis of LMCAD patients with CABG therapy.

Asunto(s)

Alelos , Puente de Arteria Coronaria , Enfermedad de la Arteria Coronaria , Ciclooxigenasa 2/genética , Polimorfismo Genético , Anciano , Enfermedad de la Arteria Coronaria/enzimología , Enfermedad de la Arteria Coronaria/genética , Enfermedad de la Arteria Coronaria/mortalidad , Enfermedad de la Arteria Coronaria/cirugía , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Factores de Riesgo , Tasa de Supervivencia

RESUMEN

BACKGROUND: This study was aimed to investigate the clinical relevance between glycoprotein Ia (GPIA) rs1126643C/T polymorphism and the outcome of coronary artery disease after coronary artery bypass graft (CABG) surgery and explore the involved potential mechanisms. METHODS AND RESULTS: We genotyped GPIA rs1126643 polymorphism of 1592 patients who underwent CABG and followed up for a median period of 72.8 months. Patients who are GPIA rs1126643 T-allele carriers have a higher major adverse cardiac or cerebrovascular events risk post-CABG than those who are CC homozygotes (hazard ratio [HR]=1.29; P=0.022). The clinical association between the risk allele (T) carriage and major adverse cardiac or cerebrovascular events was confirmed in another cohort study, which included 646 CABG patients from various health centers across China. Meanwhile, rs1126643 T allele was also linked with increased risk of major adverse cardiac or cerebrovascular events (HR=1.73; P=0.019). To explore the underlying mechanisms, we prospectively recruited 131 coronary artery disease patients, assessed their platelet aggregation function, and focused on detecting their GPIA mRNA level and protein expression. Results showed that patients with rs1126643 T allele have elevated platelet aggregation activity (P=0.029) when protein expression is increased (P<0.001) and not affected by glycoprotein Ia mRNA level. CONCLUSIONS: The synonymous common variant, GPIA rs1126643, increases the long-term adverse events risk of CABG by augmenting GPIa protein expression and enhancing platelet aggregation function. This finding can serve as the implication of improving secondary prevention of CABG patients.

Asunto(s)

Puente de Arteria Coronaria/efectos adversos , Enfermedad de la Arteria Coronaria/cirugía , ADN/genética , Integrina alfa2/sangre , Polimorfismo Genético , Complicaciones Posoperatorias/epidemiología , Western Blotting , China/epidemiología , Enfermedad de la Arteria Coronaria/sangre , Enfermedad de la Arteria Coronaria/genética , Femenino , Estudios de Seguimiento , Genotipo , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Reacción en Cadena en Tiempo Real de la Polimerasa , Estudios Retrospectivos , Tasa de Supervivencia/tendencias , Factores de Tiempo

RESUMEN

BACKGROUND: Maladaptive cardiac hypertrophy is a major risk factor for heart failure, which is the leading cause of death worldwide. C-C motif chemokine receptor 9 (CCR9), a subfamily of the G protein-coupled receptor supergene family, has been highlighted as an immunologic regulator in the development and homing of immune cells and in immune-related diseases. Recently, CCR9 was found to be involved in the pathogenesis of other diseases such as cardiovascular diseases; however, the effects that CCR9 exerts in cardiac hypertrophy remain elusive. METHODS AND RESULTS: We observed significantly increased CCR9 protein levels in failing human hearts and in a mouse or cardiomyocyte hypertrophy model. In loss- and gain-of-function experiments, we found that pressure overload-induced hypertrophy was greatly attenuated by CCR9 deficiency in cardiac-specific CCR9 knockout mice, whereas CCR9 overexpression in cardiac-specific transgenic mice strikingly enhanced cardiac hypertrophy. The prohypertrophic effects of CCR9 were also tested in vitro, and a similar phenomenon was observed. Consequently, we identified a causal role for CCR9 in pathological cardiac hypertrophy. Mechanistically, we revealed a lack of difference in the expression levels of mitogen-activated protein kinases between groups, whereas the phosphorylation of AKT/protein kinase B and downstream effectors significantly decreased in CCR9 knockout mice and increased in CCR9 transgenic mice after aortic binding surgery. CONCLUSIONS: The prohypertrophic effects of CCR9 were not attributable to the mitogen-activated protein kinase signaling pathway but rather to the AKT-mammalian target of rapamycin-glycogen synthase kinase 3ß signaling cascade.

Asunto(s)

Cardiomegalia/metabolismo , Cardiomiopatía Dilatada/metabolismo , Cardiomiopatía Hipertrófica/metabolismo , Miocitos Cardíacos/metabolismo , Receptores CCR/metabolismo , Animales , Cardiomiopatía Dilatada/diagnóstico por imagen , Cardiomiopatía Hipertrófica/diagnóstico por imagen , Glucógeno Sintasa Quinasa 3 beta/metabolismo , Humanos , Ratones , Ratones Noqueados , Ratones Transgénicos , Miocitos Cardíacos/patología , Fosforilación , Proteínas Proto-Oncogénicas c-akt/metabolismo , Ratas , Reacción en Cadena en Tiempo Real de la Polimerasa , Receptores CCR/genética , Transducción de Señal , Serina-Treonina Quinasas TOR/metabolismo

RESUMEN

Coronary artery disease is the leading cause of mortality and morbidity in the world. Left main coronary artery disease (LMCAD) is a particularly severe phenotypic form of CAD and has a genetic basis. We hypothesized that some inflammation- and hyperhomocysteinemia-related gene polymorphisms may contribute to LMCAD susceptibility in a Chinese population. We studied the association between polymorphisms in the genes hepatocyte nuclear factor 1 alpha (HNF1A; rs7310409, G/A), C-reactive protein (rs1800947 and rs3093059 T/C), methylenetetrahydrofolate reductase (rs1801133, C/T), and methylenetetrahydrofolate dehydrogenase (rs1076991, A/G) in 402 LMCAD and 804 more peripheral CAD patients in a Chinese population. Genotyping was performed using the matrix-assisted laser desorption/ionization time-of-flight mass spectrometry method. When the HNF1A rs7310409 GG homozygote genotype was used as the reference group, both the individual, GA and AA, and combined GA/AA genotypes were associated with an increased risk of LMCAD. This single nucleotide polymorphism (rs7310409) is strongly associated with plasma CRP levels. In conclusion, the present study provides evidence that the HNF1A rs7310409 G/A functional polymorphism may contribute to the risk of LMCAD.

RESUMEN

Left main coronary artery disease (LMCAD) is a particular severe phenotype of coronary artery disease (CAD) and heritability. Interleukin (IL) may play important roles in the pathogenesis of CAD. Although several single nucleotide polymorphisms (SNPs) identified in IL related genes have been evaluated for their roles in inflammatory diseases and CAD predisposition, the investigations between genetic variants and CAD phenotype are limited. We hypothesized that some of these gene SNPs may contribute to LMCAD phenotype susceptibility compared with more peripheral coronary artery disease (MPCAD). In a hospital-based case-only study, we studied IL-1A rs1800587 C/T, IL-1B rs16944 G/A, IL-6 rs1800796 C/G, IL-6R rs7529229 T/C, IL-8 rs4073 T/A, IL-10 rs1800872 A/C, and IL-10 rs1800896 A/G SNPs in 402 LMCAD patients and 804 MPCAD patients in a Chinese population. Genotyping was done using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) and ligation detection reaction (LDR) method. When the IL-6R rs7529229 TT homozygote genotype was used as the reference group, the CC or TC/CC genotypes were associated with the increased risk for LMCAD (CC vs. TT, adjusted odds ratio(OR)=1.46, 95% confidence interval (CI)=1.02-2.11, p=0.042; CC+TC vs. TT, adjusted OR=1.31, 95% CI=1.02-1.69, p=0.037). None of the other six SNPs achieved any significant differences between LMCAD and MPCAD. The present study suggests that IL-6R rs7529229 T/C functional SNP may contribute to the risk of LMCAD in a Chinese population. However, our results were limited. Validation by a larger study from a more diverse ethnic population is needed.

Asunto(s)

Enfermedad de la Arteria Coronaria/genética , Vasos Coronarios/patología , Receptores de Interleucina-6/genética , China , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Humanos , Interleucina-10/genética , Interleucina-1alfa/genética , Interleucina-1beta/genética , Interleucina-6/genética , Interleucina-8/genética , Polimorfismo de Nucleótido Simple , Factores de Riesgo , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción