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1.
Int J Biol Sci ; 16(5): 730-738, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32071544

RESUMO

The Wnt signaling pathway plays important roles in organ development and disease processes. Secreted frizzled-related protein 2 (sFRP2), a vital molecule of Wnt signaling, can regulate cardiac development and cardiovascular disease. Recent studies have suggested that sFRP2 is not only an antagonist of the canonical Wnt signaling pathway, but also has a more complex relationship in myocardial fibrosis, angiogenesis, cardiac hypertrophy and cardiac regeneration. Here, we review the role of sFRP2 and Wnt signaling in cardiac development and cardiovascular disease.

3.
Stem Cell Res Ther ; 11(1): 22, 2020 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-31918758

RESUMO

BACKGROUND: Bone marrow mesenchymal stem cell (BMSC) transplantation represents a promising therapeutic strategy for ischemic heart disease. However, its effects are hampered by the poor viability of transplanted cells and the hostile microenvironment of the ischemic region. Insulin-like growth factor-1 (IGF-1) is an important paracrine growth factor of BMSC and plays an important role in the properties of BMSC. Here, we investigated whether overexpressing IGF-1 could enhance the BMSC viability, migration, anti-apoptosis, and protective effects of cardiomyocytes, and explore the underlying mechanisms' focus on the role of the AKT/secreted frizzled-related protein 2 (SFRP2)/ß-catenin pathway. METHODS: We constructed BMSCs overexpressing insulin-like growth factor-1 (BMSCs-IGF-1) or empty vector (BMSCs-NC) using lentivirus, and evaluated cell survival, proliferation, and migration under normoxic and hypoxic conditions. Co-culture of rat cardiomyoblasts with BMSCs was performed to explore the paracrine effect of BMSCs-IGF-1 for rescuing cardiomyoblasts under hypoxia. Transplantation of BMSCs in acute myocardial infarction rats was used to explore the effect of BMSCs-IGF-1 therapy. RESULTS: BMSCs-IGF-1 exhibited a higher cell proliferation rate, migration capacity, and stemness, and were more resistant to apoptosis under hypoxia. Overexpression of IGF-1 upregulated the expression of total and nuclear ß-catenin via the AKT-secreted frizzled-related protein 2 (SFRP2) pathway, which enhanced cell survival. Inhibition of AKT or SFRP2 knockdown by siRNA significantly antagonized the effect of IGF-1 and decreased the expression of ß-catenin. The expression of ß-catenin target genes, including cyclin D1 and c-Myc, were accordingly decreased. Moreover, BMSCs-IGF-1 could rescue cardiomyoblasts from hypoxia-induced apoptosis and preserve cell viability under hypoxia. Transplantation of BMSCs-IGF-1 into myocardial infarction rats greatly reduced infarct volume than BMSCs-NC, with significantly greater expression of SFRP2 and ß-catenin. CONCLUSIONS: These results suggest that in BMSCs overexpressing IGF-1, SFRP2 is an important mediator for the enhancement of stem cell viability via activating, rather than antagonizing, the Wnt/ß-catenin pathway.

4.
Eur Arch Otorhinolaryngol ; 277(1): 9-18, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31659449

RESUMO

BACKGROUND: Plasma levels of Epstein-Barr virus (EBV) DNA have been employed to predict survival outcomes of patients with nasopharyngeal carcinoma (NPC). However, the prognostic value of subsequent EBV DNA levels (mid or post treatment) for NPC is needed to identify by a large cohort of patients. We performed a meta-analysis of studies including data from 8128 patients to evaluate the prognostic value of EBV DNA in NPC patients. METHODS: We searched PubMed, Web of Science, and the Cochrane library for prospective and retrospective studies. Hazard ratios (HRs) and confidence intervals (CIs) were extracted from the studies or calculated and pooled to assess the association between EBV DNA levels pre-treatment (pre-DNA), mid-treatment (mid-DNA), and post-treatment (post-DNA) on clinical outcomes. RESULTS: A total of 22 studies with 8128 patients was included for analysis. Pre-DNA levels predicted overall survival, progression-free survival, distant metastasis-free survival, and local-regional failure survival with HRs (95% CIs) of 2.70 (2.06, 3.54), 2.70 (2.12, 3.44), 3.49 (2.35, 5.17), and 2.00 (1.45, 2.76), respectively, and the corresponding HRs for post-DNA levels were 4.86 (3.30, 7.17), 6.29 (3.41, 11.60), 5.68 (2.71,11.93), respectively. Mid-DNA levels predicted overall survival and progression-free survival with an HR (95% CI) of 3.02 (1.54, 5.29) and 3.15 (2.05, 4.83). Subgroup analysis showed that the HR of post-DNA wasn't influenced by different detection time of post-DNA (P = 0.22, I2 = 33.2%). CONCLUSION: The EBV DNA levels have a significant prognostic impact in patients with NPC. The effect of post-treatment EBV DNA level dominated that of pre-DNA and mid-DNA levels.

7.
Curr Neuropharmacol ; 2019 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-31686629

RESUMO

Glutamate is the major excitatory neurotransmitter in the central nervous system, and its signaling is critical for excitatory synaptic transmission. The well-established glutamate system involves glutamate synthesis, presynaptic glutamate release, glutamate actions on the ionotropic glutamate receptors (NMDA, AMPA, and kainate receptors) and metabotropic glutamate receptors, and glutamate uptake by glutamate transporters. When the glutamate system becomes dysfunctional, it contributes to the pathogenesis of neurodegenerative and neuropsychiatric diseases, such as, Alzheimer's disease, Parkinson's disease, depression, epilepsy, and ischemic stroke. In this review, based on regulating glutamate signaling, we summarize the effects and underlying mechanisms of natural constituents from Chinese herbal medicines in neurological disorders. Natural constituents from Chinese herbal medicine can prevent the glutamate-mediated excitotoxicity via suppressing presynaptic glutamate release, decreasing ionotropic and metabotropic glutamate receptors expression in the excitatory synapse, and promoting astroglial glutamate transporter expression to increase glutamate clearance from the synaptic cleft. However, some natural constituents from Chinese herbal medicine have the ability to restore the collapse of excitatory synapses by promoting presynaptic glutamate release and increasing ionotropic and metabotropic glutamate receptors expression. These regulatory processes involve various signaling pathways, which lead to different mechanistic routes of protection against neurological disorders. Hence, our review addresses the underlying mechanisms of natural constituents from Chinese herbal medicines that regulate glutamate systems and serve as promising agents for the treatment of the above-mentioned neurological disorders.

8.
BMJ Open ; 9(9): e031180, 2019 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-31530618

RESUMO

OBJECTIVE: To examine the real-world patterns of oral anticoagulant (OAC) therapy in patients with acute coronary syndrome (ACS) and atrial fibrillation (AF) in Southern China undergoing percutaneous coronary intervention (PCI) and determine the clinical characteristics associated with OAC prescription. DESIGN: A retrospective cohort study. SETTING: This study was conducted in the Shunde Hospital, Southern Medical University and the second hospital of Zhaoqing, China, from January 2013 to 31 December 2018. PARTICIPANTS: Patients were aged ≥18 years, hospitalised for ACS and received PCI treatment. OUTCOME MEASURES: AF was diagnosed based on an ECG recording or a Holter monitor. Prescription of OACs and antiplatelets were determined from the discharge medication list. RESULTS: A total of 3612 patients with ACS were included: 286 (7.9%) were diagnosed with AF, including 45 (1.2%) with paroxysmal AF, 227 (6.3%) with persistent/permanent AF and 14 (0.4%) with unclassified AF. Although 95.5% of patients with AF were at high risk (CHA2DS2-VASc score ≥2) of stroke, only 21.7% of them were discharged on OACs (10.5% received warfarin and 11.2% received non-vitamin K antagonist OACs). Patients with pre-admission use of OAC, a HAS-BLED score <3, with persistent/permanent AF were more likely to receive OAC treatment at discharge. CONCLUSION: We found that approximately 8% of patients who underwent PCI during ACS hospitalisation also demonstrated AF. Anticoagulant therapy was greatly underused. Patients with paroxysmal AF and an increased risk of bleeding were less likely to receive anticoagulant treatment. Further efforts should be made to increase the adherence to guideline recommendations for OACs.

9.
J Hum Hypertens ; 2019 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-31431682

RESUMO

The 2017 American College of Cardiology (ACC)/American Heart Association (AHA) lowered the diagnostic criteria for hypertension. We aimed to explore whether clustering of multiple risk factors are associated with the risk of new-onset hypertension defined by the 2017 ACC/AHA Hypertension Guideline. Subjects who attended ≥2 annual health examinations without baseline hypertension and cardiovascular disease were included. Hypertension was defined according to the 2017 ACC/AHA Hypertension Guideline. Seven predefined risk factors, including age, resting heart rate, overweight or obesity, dyslipidemia, hyperuricemia, impaired glucose regulation, and a poor estimated glomerular filtration rate, were analyzed. A composite, individual-level, cumulative score incorporating these seven risk factors (no = 0 point; yes = 1 point; total range of 0-7 points) was calculated. The association between the cumulative score and the risk of hypertension was analyzed using a Cox regression model. A total of 4424 (21.6%) of 20,190 subjects included had new-onset hypertension during a follow-up duration of 3.6 years. Compared with subjects with 0 points, the adjusted hazard ratios (95% confidence intervals) for the development of hypertension for those with 1, 2, 3, and ≥4 points were 1.21 (1.07-1.38), 1.34 (1.19-1.52), 1.44 (1.26-1.63), and 1.64 (1.44-1.87), respectively (P < 0.001), after adjustment for sex and baseline blood pressure. Age, resting heart rate, overweight/obesity, dyslipidemia, hyperuricemia, impaired glucose regulation, and a poor estimated glomerular filtration rate are associated with an increased risk of future hypertension. When these factors are combined, there is an accumulated increase in risk.

10.
BMC Cardiovasc Disord ; 19(1): 135, 2019 06 03.
Artigo em Inglês | MEDLINE | ID: mdl-31159740

RESUMO

BACKGROUND: Effects of ß-blockers on outcomes in patients with chronic heart failure (CHF) and atrial fibrillation (AF) is still in controversy. METHODS: Searching was conducted by using keywords "atrial fibrillation", and "heart failure" in PubMed, MEDLINE and Embase databases before November 30, 2017. Prospective studies [i.e. randomized control trials (RCTs), post-hoc analysis of RCTs, prospective cohort studies and registry studies] that studied the effect of ß-blockers and all-cause mortality in patients with CHF and AF were included. The analysis was stratified by study design. RESULTS: We identified 12 studies, including 6 post-hoc analysis of RCTs and 6 observational studies (including prospective registry studies and prospective cohort studies), which enrolled 38,133 patients with CHF and AF. Overall, ß-blockers treatment was associated with significant decrease in all-cause mortality [Risk Ratio (RR) =0.73; 95% Confidence Interval (CI) 0.65-0.82, P < 0.001]. When stratified by study design, ß-blockers treatment was associated with 34% reduction in patients with CHF and AF in observational study (RR = 0.66; 95% CI 0.58-0.76, P < 0. 001), but not in post-hoc analysis of RCT (RR = 0.87; 95% CI 0.74-1.02, P = 0.09). CONCLUSIONS: ß-blockers treatment was associated with significantly decrease the risk of all-cause mortality in patients with AF-CHF and it was only seen in observational study group, but not in subgroup analysis of RCT group. Further large RCTs are required to verify the effect of ß-blockers treatment on patients with CHF and AF. The main limitation of this study is the lack of individual data on patients in each study.

11.
Biomed Res Int ; 2019: 8642784, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31236414

RESUMO

Background: The association between lipoprotein-associated phospholipase A2 (Lp-PLA2) and stroke risk is inconsistent. We conducted a meta-analysis to determine whether elevated Lp-PLA2 is a risk factor for stroke. Methods: Studies were included if they reported Lp-PLA2 mass and/or activity levels and adjusted risk estimates of stroke. The primary outcome was overall stroke incidence. The combined results were shown as relative risks (RRs) with 95% confidence intervals (CI) for per 1 standard deviation (SD) higher value of Lp-PLA2 and the highest versus lowest Lp-PLA2 category. Results: Twenty-two studies involving 157,693 participants were included for analysis. After adjusting for conventional risk factors, the RRs for overall stroke with 1 SD higher Lp-PLA2 activity and mass were 1.07 (95% CI 1.02-1.13) and 1.11 (95% CI 1.04-1.19), respectively. The RRs of ischemic stroke with 1 SD higher Lp-PLA2 activity and mass were 1.08 (95% CI 1.01-1.15) and 1.11 (95% CI 1.02-1.22), respectively. When comparing the highest and lowest levels of Lp-PLA2, the RRs of stroke for Lp-PLA2 activity and mass were 1.26 (95% CI 1.03-1.54) and 1.56 (95% CI 1.21-2.00), respectively. Finally, when comparing the highest and lowest levels of Lp-PLA2, the pooled RRs of ischemic stroke for Lp-PLA2 activity and mass were 1.29 (95% CI 1.07-1.56) and 1.68 (95% CI 1.12-2.53), respectively. Conclusions: Elevated baseline Lp-PLA2 levels, detected either by activity or mass, are associated with increased stroke risk.


Assuntos
1-Alquil-2-acetilglicerofosfocolina Esterase/sangue , Biomarcadores/sangue , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/epidemiologia , 1-Alquil-2-acetilglicerofosfocolina Esterase/genética , Idoso , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Acidente Vascular Cerebral/genética , Acidente Vascular Cerebral/patologia
13.
J Hypertens ; 37(4): 696-701, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30817449

RESUMO

OBJECTIVES: This study aimed to develop a cumulative score composed of seven risk factors: age, resting heart rate, overweight or obesity, dyslipidemia, hyperuricemia, impaired glucose regulation, and impaired estimated glomerular filtration rate (eGFR), to evaluate the risk of new-onset hypertension. METHODS: We retrospectively conducted a cohort study in 23 665 participants free from hypertension at baseline, who attended at least two annual health examinations between 2011 and 2016. We defined hypertension as SBP of 140 mmHg or less and/or DBP of at least 90 mmHg, according to the 2010 Chinese guidelines for the management of hypertension. We computed a composite, individual-level cumulative score incorporating all seven risk factors (no = 0 point; yes = 1 point; total range 0-7 points). Cox regression was used to analyze the association between cumulative score and risk of hypertension. RESULTS: A total of 2305 participants developed hypertension during a median follow-up period of 3.6 years. Compared with participants with 0 points, the adjusted hazard ratios (95% confidence intervals) for the development of hypertension for those with 2, 3, and at least 4 points were 1.61 (1.29-2.02), 2.05 (1.64-2.57) and 2.77 (2.22-3.46), respectively (P trend < 0.001). This association was present after adjustment for sex and baseline blood pressure. CONCLUSION: Age, resting heart rate, overweight or obesity, dyslipidemia, hyperuricemia, impaired glucose regulation, and impaired eGFR were associated with significant risk of new-onset hypertension and when combined there was an accumulation of risk.

14.
Int J Health Care Qual Assur ; 32(1): 59-70, 2019 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-30859880

RESUMO

PURPOSE: The purpose of this paper is to develop a chemotherapy scheduling template that accounts for nurse resource availability and patient treatment needs to alleviate the mid-day patient load and provide quality services for patients. DESIGN/METHODOLOGY/APPROACH: Owing to treatment complexity in chemotherapy administration, nurses are required at the beginning, end and during treatment. When nurses are not available to continue treatment, the service is compromised, and the resource constraint is violated, which leads to inevitable delay that risks service quality. Consequently, an optimization method is used to create a scheduling template that minimizes the violation between resource assignment and treatment requirements, while leveling patient load throughout a day. A case study from a typical clinic day is presented to understand current scheduling issues, describe nursing resource constraints, and develop a constraint-based optimization model and leveling algorithm for the final template. FINDINGS: The approach is expected to reduce the variation in the system by 24 percent and result in five fewer chemo chairs used during peak hours. Adjusting staffing levels could further reduce resource constraint violations and more savings on chair occupancy. The actual implementation results indicate a 33 percent reduction on resource constraint violations and positive feedback from nursing staff for workload. RESEARCH LIMITATIONS/IMPLICATIONS: Other delays, including laboratory test, physician visit and treatment assignment, are potential research areas. ORIGINALITY/VALUE: The study demonstrates significant improvement in mid-day patient load and meeting treatment needs using optimization with a unique objective.


Assuntos
Tratamento Farmacológico/normas , Enfermagem Oncológica/organização & administração , Admissão e Escalonamento de Pessoal/organização & administração , Gestão da Qualidade Total/organização & administração , Carga de Trabalho , Centros Médicos Acadêmicos , Assistência Ambulatorial/organização & administração , Tratamento Farmacológico/tendências , Feminino , Humanos , Masculino , Minnesota , Relações Enfermeiro-Paciente , Recursos Humanos de Enfermagem no Hospital/organização & administração , Segurança do Paciente , Pesquisa Qualitativa
19.
J Hypertens ; 2018 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-30300252

RESUMO

OBJECTIVES: This study aimed to develop a cumulative score composed of seven risk factors: age, resting heart rate, overweight or obesity, dyslipidemia, hyperuricemia, impaired glucose regulation, and impaired estimated glomerular filtration rate (eGFR), to evaluate the risk of new-onset hypertension. METHODS: We retrospectively conducted a cohort study in 23 665 participants free from hypertension at baseline, who attended at least two annual health examinations between 2011 and 2016. We defined hypertension as SBP of 140 mmHg or less and/or DBP of at least 90 mmHg, according to the 2010 Chinese guidelines for the management of hypertension. We computed a composite, individual-level cumulative score incorporating all seven risk factors (no = 0 point; yes = 1 point; total range 0-7 points). Cox regression was used to analyze the association between cumulative score and risk of hypertension. RESULTS: A total of 2305 participants developed hypertension during a median follow-up period of 3.6 years. Compared with participants with 0 points, the adjusted hazard ratios (95% confidence intervals) for the development of hypertension for those with 2, 3, and at least 4 points were 1.61 (1.29-2.02), 2.05 (1.64-2.57) and 2.77 (2.22-3.46), respectively (P trend < 0.001). This association was present after adjustment for sex and baseline blood pressure. CONCLUSION: Age, resting heart rate, overweight or obesity, dyslipidemia, hyperuricemia, impaired glucose regulation, and impaired eGFR were associated with significant risk of new-onset hypertension and when combined there was an accumulation of risk.

20.
Dis Markers ; 2018: 2429160, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30245751

RESUMO

Background: Serum gamma-glutamyltransferase (GGT) is a biomarker of hepatic disease. Recent studies have shown that GGT may also associate with the risk of coronary artery disease. However, the underlying mechanisms of this association are still unclear. Methods: This study included 216 young patients with acute coronary syndrome (aged ≤55years) and 227 age-matched controls with normal findings by coronary angiography or coronary computed tomography angiography. We use standard colorimetric techniques and sandwich enzyme-linked immunosorbent assay to measure the levels of GGT and oxidized low-density lipoprotein (ox-LDL), respectively. Traditional risk factors of coronary artery disease, including smoking, diabetes mellitus, hypertension, dyslipidemia, and obesity/overweight, were evaluated according to the current guidelines. Results: The levels of GGT were significantly correlated with body mass index and levels of triglyceride, fasting plasma glucose, aspartate aminotransferase, and ox-LDL (all P < 0.05). Multivariate logistic regression analysis showed that GGT was significantly associated with the risk of acute coronary syndrome in young Chinese patients (OR = 1.53, 95% CI = 1.09-2.15) after adjusting for traditional risk factors, including sex, age, quantity of smoking, hypertension, diabetes, body mass index, dyslipidemia, and high-sensitivity C-reactive protein. However, this association was significantly attenuated (OR = 1.20, 95% CI = 0.91-1.58) after further adjusting for the levels of ox-LDL. Conclusions: GGT was associated with the risk of ACS in relatively young patients. The link between GGT and the risk of ACS may be dependent on ox-LDL levels, indicating that the prooxidant action is an important pathway for GGT in the development of cardiovascular disease.


Assuntos
Síndrome Coronariana Aguda/sangue , gama-Glutamiltransferase/sangue , Síndrome Coronariana Aguda/etiologia , Adulto , Grupo com Ancestrais do Continente Asiático , Estudos de Casos e Controles , Feminino , Humanos , Lipoproteínas LDL/sangue , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Fatores de Risco
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