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Objective: To investigate the prevalence and associated risk of cardiovascular event of resistant hypertension in treated outpatients. Methods: This study was a nationwide multi-center prospective cohort study. The participants were treated outpatients enrolled in the China Nationwide Ambulatory and Home Blood Pressure Registry study of 42 hospitals in 19 provinces across the country from August 2009 to October 2017. Apparent resistant hypertension was defined as uncontrolled office blood pressure (≥140/90 mmHg, 1 mmHg=0.133 kPa) in spite of the use of three antihypertensive drugs or controlled office blood pressure (<140/90 mmHg) with four antihypertensive drugs or more. Subjects diagnosed with uncontrolled office blood pressure were further subdivided as pseudo-resistant hypertension and true resistant hypertension based on 24 h ambulatory blood pressure monitoring. The primary endpoint was fatal and non-fatal cardiovascular and cerebrovascular events, which was a composite endpoint consisting of cardiovascular and cerebrovascular death, ischemic and hemorrhagic stroke, myocardial infarction, coronary artery revascularization, unstable angina, heart failure, and coronary artery stenosis≥50% confirmed by coronary angiography. Secondary outcomes included fatal and non-fatal stroke or cardiac events. Patients with controlled office blood pressure after taking only 1 or 2 antihypertensive drugs were included as control. Kaplan-Meier survival curves, log-rank test, and Cox proportional risk model were used to evaluate the risk of apparent refractory hypertension in relation to cardiovascular and cerebrovascular prognosis. Results: A total of 2 782 treated hypertensive patients, aged (58.1±12.3) years were enrolled, including 1 403 (50.4%) men. The prevalence of apparent and true resistant hypertension was 15.1% (420/2 782) and 10.5% (293/2 782), respectively. Among patients with apparent resistant hypertension, during a median of 5 years follow-up, the cumulative incidence rate was 28.2, 11.2 and 19.1 per 1 000 person-years for fatal and non-fatal cardiovascular events (n=58), stroke (n=24) and cardiac events (n=40), respectively. The Kaplan-Meier curve and log-rank test showed that those patients with true resistant hypertension, had the highest cumulative incidence rate of fatal and non-fatal cardiovascular events, stroke, and cardiac events. Multivariable Cox regression analyses showed that true resistant hypertension was associated with a significantly higher risk of fatal and non-fatal cardiovascular events (HR=1.73, 95%CI 1.17-2.56, P=0.006) and stroke (HR=2.81, 95%CI 1.53-5.17, P=0.001). Conclusion: Resistant hypertension, especially true resistant hypertension, is associated with a higher risk of fatal and non-fatal cardiac and cerebrovascular events.
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Anti-Hipertensivos , Hipertensão , Pacientes Ambulatoriais , Humanos , Hipertensão/epidemiologia , Hipertensão/complicações , Estudos Prospectivos , Anti-Hipertensivos/uso terapêutico , Prognóstico , Fatores de Risco , Pressão Sanguínea , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/etiologia , Doenças Cardiovasculares/epidemiologia , China/epidemiologia , Masculino , Feminino , Pessoa de Meia-Idade , PrevalênciaRESUMO
Objective: To analyze the clinical characteristics and risk factors of malignant vasovagal syncope (VVS) in children. Methods: This was a case-control study. The data of 368 VVS patients who were treated in the Department of Cardiology, Children's Hospital, Capital Institute of Pediatrics from June 2017 to December 2021 was collected and analyzed. They were divided into malignant VVS group and non-malignant VVS group according to the presence of sinus arrest, and then their demographic characteristics were compared. The children with malignant VVS and complete clinical information were recruited into the case group and were matched by age and sex (1â¶4 ratio) with non-malignant VVS patients during the same period.Their clinical characteristics and lab tests were compared. Independent sample t test, Mann Whitney U or χ2 test was used for comparison between groups.Logistic regression was used to analyze the risk factors for malignant VVS in children. Results: Eleven malignant VVS and 342 non-malignant VVS met the inclusion and exclusion critera. Eleven malignant VVS and 44 non-malignant children were recruited in the case-control study. Ten patients of the 11 malignant VVS had a cardiac arrest occurring at 35 (28, 35) minutes of the head-up tilt test, and the duration of sinus arrest was (9±5) s. One patient had syncope occurring while waiting for drawing blood, and the duration of sinus arrest was 3.4 s. The children with malignant vasovagal syncope were younger than non-malignant VVS patients (9 (7, 10) vs. 12 (10, 14) years old, P<0.05), and had higher mean corpuscular hemoglobin concentration (MCHC) and standard deviation of the mean cardiac cycle over 5-minute period within 24 hours ((347±9) vs. (340±8) g/L, (124±9) vs. (113±28) ms, both P<0.05). Logistic regression analysis showed that MCHC was an independent risk factor for malignant VVS in pediatric patients (OR=1.13, 95%CI 1.02-1.26, P=0.024). Conclusions: The onset age of malignant VVS was younger, with no other special clinical manifestations. MCHC was an independent risk factor for malignant VVS.
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Síncope Vasovagal , Humanos , Criança , Adolescente , Síncope Vasovagal/etiologia , Estudos de Casos e Controles , Síncope , Fatores de RiscoRESUMO
PURPOSE: Papillary thyroid carcinoma (PTC) represents the most common subtype of thyroid cancer (TC). This study was set out to explore the potential effect of CHD1L on PTC and type 2 diabetes mellitus (T2DM). METHODS: We searched for T2DM susceptibility genes through the GWAS database and obtained T2DM-related differentially expressed gene from the GEO database. The expression and clinical data of TC and normal samples were collated from the TCGA database. Receiver operating characteristic (ROC) curve analysis was subsequently applied to assess the sensitivity and specificity of the CHD1L for the diagnosis of PTC. The MCP-counter package in R language was then utilized to generate immune cell score to evaluate the relationship between CHD1L expression and immune cells. Then, we performed functional enrichment analysis of co-expressed genes and DEGs to determine significantly enriched GO terms and KEGG to predict the potential functions of CHD1L in PTC samples and T2DM adipose tissue. RESULTS: From two genes (ABCB9, CHD1L) were identified to be DEGs (p < 1 * 10-5) that exerted effects on survival (HR > 1, p < 0.05) in PTC and served as T2DM susceptibility genes. The gene expression matrix-based scoring of immunocytes suggested that PTC samples with high and low CHD1L expression presented with significant differences in the tumor microenvironment (TME). The enrichment analysis of CHD1L co-expressed genes and DEGs suggested that CHD1L was involved in multiple pathways to regulate the development of PTC. Among them, Kaposi sarcoma-associated herpesvirus infection, salmonella infection and TNF signaling pathways were highlighted as the three most relevant pathways. GSEA analysis, employed to analyze the genome dataset of PTC samples and T2DM adipose tissue presenting with high and low expression groups of CHD1L, suggests that these differential genes are related to chemokine signaling pathway, leukocyte transendothelial migration and TCELL receptor signaling pathway. CONCLUSION: CHD1L may potentially serve as an early diagnostic biomarker for PTC, and a target of immunotherapy for PTC and T2DM.
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Biomarcadores Tumorais/metabolismo , Biologia Computacional/métodos , DNA Helicases/metabolismo , Proteínas de Ligação a DNA/metabolismo , Diabetes Mellitus Tipo 2/fisiopatologia , Estudo de Associação Genômica Ampla , Câncer Papilífero da Tireoide/patologia , Neoplasias da Glândula Tireoide/patologia , Biomarcadores Tumorais/genética , DNA Helicases/genética , Proteínas de Ligação a DNA/genética , Seguimentos , Humanos , Prognóstico , Câncer Papilífero da Tireoide/genética , Câncer Papilífero da Tireoide/metabolismo , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/metabolismo , Microambiente TumoralRESUMO
We investigated the association of plasma AGE (advanced glycation end product) concentration with central and peripheral blood pressures and central-to-brachial blood pressure amplification in a Chinese population. The study subjects were from a newly established residential area in the suburb of Shanghai. Using the SphygmoCor system, we recorded radial arterial waveforms and derived aortic waveforms by a generalized transfer function and central systolic and pulse pressure by calibration for brachial blood pressure measured with an oscillometric device. The central-to-brachial pressure amplification was expressed as the central-to-brachial systolic blood pressure difference and pulse pressure difference and ratio. Plasma AGE concentration was measured by the enzyme-linked immunosorbent assay method and logarithmically transformed for statistical analysis. The 1051 participants (age, 55.1±13.1 years) included 663 women. After adjustment for sex, age and other confounding factors, plasma AGE concentration was associated with central but not peripheral blood pressures and with some of the pressure amplification indexes. Indeed, each 10-fold increase in plasma AGE concentration was associated with 2.94 mm Hg (P=0.04) higher central systolic blood pressure and 2.39% lower central-to-brachial pulse pressure ratio (P=0.03). In further subgroup analyses, the association was more prominent in the presence of hypercholesterolemia (+8.11 mm Hg, P=0.008) for central systolic blood pressure and in the presence of overweight and obesity (-4.89%, P=0.009), diabetes and prediabetes (-6.26%, P=0.10) or current smoking (-6.68%, P=0.045) for central-to-brachial pulse pressure ratio. In conclusion, plasma AGE concentration is independently associated with central systolic blood pressure and pulse pressure amplification, especially in the presence of several modifiable cardiovascular risk factors.
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Pressão Sanguínea , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/fisiopatologia , Produtos Finais de Glicação Avançada/sangue , Adulto , Idoso , Biomarcadores/sangue , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/etiologia , China , Estudos Transversais , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Oscilometria/instrumentação , Análise de Onda de Pulso , Medição de Risco , Fatores de Risco , Rigidez VascularRESUMO
The cloning of a Pax6 orthologue from the sepiolid squid Euprymna scolopes and its developmental expression pattern are described. The data are consistent with the presence of a single gene encoding a protein with highly conserved DNA-binding paired and homeodomains. A detailed expression analysis by in situ hybridization and immunodetection revealed Pax6 mRNA and protein with predominantly nuclear localization in the developing eye, olfactory organ, brain lobes (optic lobe, olfactory lobe, peduncle lobe, superior frontal lobe and dorsal basal lobe), arms and mantle, suggestive of a role in eye, brain, and sensory organ development.
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Encéfalo/embriologia , Decapodiformes/embriologia , Olho/embriologia , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismo , Órgãos dos Sentidos/embriologia , Sequência de Aminoácidos , Animais , Encéfalo/metabolismo , Núcleo Celular/metabolismo , Clonagem Molecular , Decapodiformes/genética , Embrião não Mamífero , Olho/metabolismo , Proteínas do Olho/genética , Proteínas do Olho/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , Dados de Sequência Molecular , Fator de Transcrição PAX6 , Fatores de Transcrição Box Pareados , Proteínas Repressoras , Órgãos dos Sentidos/metabolismo , Homologia de Sequência de AminoácidosRESUMO
In order to develop an effective strategy of breast cancer therapy targeting survivin and its splice variants survivin-ΔEx3 and survivin-2B, the present study constructed four expression vectors by fusing the survivin antisense gene, the survivin (T34A) gene, the survivin-ΔEx3 antisense gene, and the survivin-2B gene with the enhanced green fluorescent protein (eGFP) gene. Each of these vectors was transiently transfected into the B-Cap-37 human breast cancer cell line. The effects of these four vectors with diverse genes on the proliferation and apoptosis of B-Cap-37 breast cancer cells were examined and compared in vitro using MTT and flow cytometry assays. Results of the MTT assay indicated that all four gene therapy plasmids were most effective at inhibiting the proliferation of B-Cap-37 cells 72 h after transfection. However, the four gene therapies had different rates of cell inhibition. pcDNA3.1(+)-egfp-anti-survivin and pcDNA3.1(+)-survivin (T34A)-egfp had almost equivalent or better effectiveness at suppressing cell growth. pcDNA3.1(+)-egfp-anti-survivin-ΔEx3 moderately inhibited the growth of B-Cap-37 cells. In contrast, pcDNA3.1(+)-survivin-2B-egfp had limited inhibition of cell growth. Similar profile of effectiveness of four gene therapies in soliciting cell apoptosis was also observed. These results suggest the relative importance of targeting survivin and its splice variant survivin-ΔEx3 in breast cancer treatment.
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The role of Na(+), K(+), Cl(-)-cotransport (NKCC) in apoptosis of HepG2 human hepatoblastoma cells was investigated. Pinacidil (Pin), an activator of ATP-sensitive K(+) (K(ATP)) channels, induced apoptosis in a dose- and time-dependent manner in HepG2 cells. Pin increased intracellular K(+) concentration ([K(+)](i)). Bumetanide and furosemide, NKCC inhibitors, significantly inhibited the Pin-induced increased [K(+)](i) and apoptosis, whereas K(ATP) inhibitors (glibenclamide and tolbutamide) had no effects. The Pin-induced [K(+)](i) increase was significantly prevented by reducing extracellular Cl(-) concentration, and Pin also increased intracellular Na(+) concentration ([Na(+)](i)), further indicating that these effects of Pin may be due to NKCC activation. In addition, Pin induced a rapid and sustained increase in intracellular Ca(2+) concentration ([Ca(2+)](i)), which was completely prevented by the NKCC inhibitors. Treatment with EGTA or BAPTA/AM markedly inhibited the Pin-induced apoptosis. Inhibitors of Na(+), Ca(2+)-exchanger, bepridil, and benzamil significantly prevented both [Ca(2+)](i) increase and apoptosis induced by Pin. Taken together, these results suggest that Pin increases [Na(+)](i) through NKCC activation, which leads to stimulation of reverse-mode of Na(+), Ca(2+) exchanger, resulting in [Ca(2+)](i) increase, and in turn, apoptosis. These results further suggest that NKCC may be a good target for induction of apoptosis in human hepatoma cells.
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Apoptose/efeitos dos fármacos , Cálcio/metabolismo , Proteínas de Transporte/efeitos dos fármacos , Hepatoblastoma/patologia , Pinacidil/farmacologia , Trifosfato de Adenosina/fisiologia , Amilorida/análogos & derivados , Amilorida/farmacologia , Bepridil/farmacologia , Bumetanida/farmacologia , Proteínas de Transporte/fisiologia , Fragmentação do DNA/efeitos dos fármacos , Relação Dose-Resposta a Droga , Furosemida/farmacologia , Glibureto/farmacologia , Hepatoblastoma/metabolismo , Humanos , Potássio/metabolismo , Bloqueadores dos Canais de Potássio , Canais de Potássio/fisiologia , Sódio/metabolismo , Trocador de Sódio e Cálcio/antagonistas & inibidores , Trocador de Sódio e Cálcio/metabolismo , Simportadores de Cloreto de Sódio-Potássio , Fatores de Tempo , Tolbutamida/farmacologia , Células Tumorais CultivadasRESUMO
A role for the Pax-6 homologue eyeless in adult Drosophila brain development and function is described. eyeless expression is detected in neurons, but not glial cells, of the mushroom bodies, the medullar cortex, the lateral horn, and the pars intercerebralis. Furthermore, severe defects in adult brain structures essential for vision, olfaction, and for the coordination of locomotion are provoked by two newly isolated mutations of Pax-6/eyeless that result in truncated proteins. Consistent with the morphological lesions, we observe defective walking behavior for these eyeless mutants. The implications of these data for understanding postembryonic brain development and function in Drosophila are discussed.