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OBJECTIVE: Primary aldosteronism (PA) is an underdiagnosed cause of hypertension. Although the medical costs will increase if all patients with elevated blood pressure are screened, the number of missed diagnosed patients with PA and the medical resources subsequently consumed by adverse cardiovascular and cerebrovascular events can be reduced. This study aimed to conduct economic evaluation PA screening strategies in Chinese patients with hypertension, that is PA screening in patients with high-risk hypertension and all patients with hypertension, to determine the cost-effective method. METHODS: The decision tree and Markov model were constructed using TreeAge Pro 2020. Using the latter, a 30-year course of hypertension after different screening strategies was simulated, with a cycle of one year. The model parameters included epidemiological data, clinical efficacy, cost and effectiveness. The total cost of treatment and quality-adjusted life year (QALY) were simulated to conduct a cost-effectiveness analysis. Univariate and probabilistic sensitivity analyses of the model were also performed. RESULTS: PA screening patients with high-risk hypertension and all patients with hypertension obtained 15.75 and 15.77 QALYs and the costs were $2488.39 and $2482.15, respectively. The strategy of PA screening in all patients with hypertension is cost-saving and produces more health outcomes. The sensitivity analysis showed that the results were reliable. CONCLUSION: From the perspective of China's health system, the strategy of screening all hypertensive patients for PA may be more cost-effective than screening only high-risk patients and providing standard antihypertensive treatment for low-risk hypertensive patients.
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Hiperaldosteronismo , Hipertensión , Antihipertensivos , China , Análisis Costo-Beneficio , Humanos , Hiperaldosteronismo/diagnóstico , Hipertensión/diagnóstico , Cadenas de Markov , Tamizaje MasivoRESUMEN
BACKGROUND: Few studies have focused on the association between lifestyle and subclinical hypothyroidism (SCH). The purpose of this study was to investigate the association between lifestyle and thyroid function in SCH. METHODS: This study was a part of a community-based and cross-sectional study, the Epidemiological Survey of Thyroid Diseases in Fujian Province, China. A total of 159 participants with SCH (81 males and 78 females) and 159 euthyroid (87 males and 72 females) participants without any missing data were included in the analysis. General information and lifestyle information including sleep, exercise, diet and smoking habits of the participants was collected by questionnaire and Pittsburgh sleep quality index scale (PSQI) was collected. Thyroid stimulating hormone (TSH), free thyroxine (FT4), thyroid peroxidase antibody (TPOAb), thyroid globulin antibody (TgAb) and urine iodine concentration (UIC) were tested. Thyroid homeostasis parameter thyroid' s secretory capacity (SPINA-GT), Jostel's TSH index (TSHI), thyrotroph T4 sensitivity index (TTSI) were calculated. Logistic regression and multiple linear regression were performed to assess associations. RESULTS: Compared with euthyroid subjects, patients with SCH were more likely to have poor overall sleep quality (15.1 vs.25.8 %, P = 0.018) and l less likely to stay up late on weekdays (54.7 vs. 23.9 % P < 0.001). In SCH group, exercise was the influencing factor of TSH (ß= -0.224, P = 0.004), thyroid secretory capacity (ß = 0.244, P = 0.006) and thyrotropin resistance (ß = 0.206, P = 0.009). Iodine excess was the influencing factor of thyroid secretory capacity (ß = 0.209, P = 0.001) and pituitary thyroid stimulating function (ß = 0.167, P = 0.034). Smoking was the influencing factor of pituitary thyroid stimulating function (ß = 0.161, P = 0.040). Staying up late on weekends was the influencing factor of thyroid secretory capacity (ß = 0.151, P = 0.047). After adjusting for possible confounders, logistic regression showed that those with poor overall sleep quality assessed by PSQI and iodine excess had an increased risk of SCH (OR 2.159, 95 %CI 1.186-3.928, P = 0.012 and OR 2.119, 95 %CI 1.008-4.456, P = 0.048, respectively). CONCLUSIONS: Lifestyle including sleep, smoking, diet and exercise was closely related to thyroid function especially thyroid homeostasis in SCH.
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Hipotiroidismo/epidemiología , Estilo de Vida , Hormonas Tiroideas/metabolismo , Adulto , China/epidemiología , Estudios Transversales , Femenino , Estudios de Seguimiento , Humanos , Hipotiroidismo/metabolismo , Masculino , PronósticoRESUMEN
High-sugar and high-fat diets cause significant harm to health, especially via metabolic diseases. In this study, the protective effects of the antidiabetic drug exenatide (synthetic exendin-4), a glucagon-like peptide 1 (GLP-1) receptor agonist, on high-fat and high-glucose (HFHG)-induced renal injuries were investigated in vivo and in vitro. In vivo and in vitro renal injury models were established. Metabolomic analysis based on 1H-nuclear magnetic resonance was performed to examine whether exenatide treatment exerts a protective effect against kidney injury in diabetic rats and to explore its potential molecular mechanism. In vivo, 8 weeks of exenatide treatment resulted in the regulation of most metabolites in the diabetes mellitus group. In vitro results showed that exendin-4 restored the mitochondrial functions of mesangial cells, which were perturbed by HFHG. The effects of exendin-4 included the improved antioxidant capacity of mesangial cells, increased the Bcl-2/Bax ratio, and reduced protein expression of cyt-c and caspase-3 activation. In addition, exendin-4 restored mesangial cell energy metabolism by increasing succinate dehydrogenase and phosphofructokinase activities and glucose consumption while inhibiting pyruvate dehydrogenase E1 activity. In conclusion, GLP-1 agonists improve renal injury in diabetic rats by ameliorating metabolic disorders. This mechanism could be partially related to mitochondrial functions and energy metabolism.
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Type 2 diabetes mellitus (T2DM) is known as a complex genetic disease characterized by genetic and environmental factors. The imbalanced intestinal flora and intestinal mucosal barrier are considered to be related to T2DM. Curcumin has been proved to affect the progression of T2DM. T2DM animal was established by low-dose streptozotocin intraperitoneal injection combined with high-fat diet (HFD) feeding. Hematoxylin and eosin (HE) staining and transfer electron microscopy (TEM) were used to observe morphological changes of intestinal tissues of T2DM rats. Insulin and glucose tolerance tests were performed to investigate the influence of curcumin on blood glucose. Curcumin significantly improved the intestinal integrity, hyperglycemia and insulin resistance in diabetic rats. The metabolic endotoxemia induced by HFD in diabetic rats was inhibited remarkably. Curcumin reversed gut microbiota dysbiosis in diabetic rats caused by HFD. We demonstrated that curcumin could protect intestinal mucosal barrier, improve insulin resistance and reduce blood glucose in diabetic rats. This study might provide experimental evidence for the prevention and treatment in T2DM.
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Curcumina/farmacología , Diabetes Mellitus Tipo 2/complicaciones , Endotoxemia/metabolismo , Microbioma Gastrointestinal , Intestinos/patología , Intestinos/fisiopatología , Animales , Bacteroidetes/fisiología , Bifidobacterium/fisiología , Dieta Alta en Grasa , Endotoxemia/complicaciones , Firmicutes/fisiología , Microbioma Gastrointestinal/efectos de los fármacos , Ontología de Genes , Hiperglucemia/complicaciones , Resistencia a la Insulina , Intestinos/efectos de los fármacos , Lipopolisacáridos , Metabolómica , Ratones , FN-kappa B/metabolismo , Ratas , Transducción de Señal/efectos de los fármacos , Proteínas de Uniones Estrechas/metabolismo , Receptor Toll-Like 4/metabolismo , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
OBJECTIVE: It remains unknown whether obesity has an effect on the pituitary-thyroid feedback control axis in subclinical hypothyroidism (SCH). We aimed to investigate the association of thyroid homeostasis with obesity in a SCH population. METHODS: Our study consisted of a community-based and cross-sectional study from the Epidemiological Survey of Thyroid Diseases in Fujian Province, China. A total of 193 subjects with SCH (90 males and 103 females) without a history of treatment of thyroid disease, such as surgery, radiation, and thyroid hormone or antithyroid medication, were included in the present study. Indices of obesity, including body mass index (BMI), waist circumference (WC), and waist-height ratio (WHtR) were measured. RESULTS: Our results showed that the secretory capacity of the thyroid gland (SPINA-GT) and Jostel's thyrotropin index (TSHI) were negatively correlated with BMI, WC, and WHtR, whereas the reciprocal of the thyrotroph thyroid hormone resistance index (TTSI-1) was positively correlated with BMI (all p < 0.05). After adjustment for age, sex, smoking, iodine status, and glucolipid metabolism, the associations between TSHI, TTSI (reciprocal transformation), and BMI still persisted (all p < 0.05). CONCLUSIONS: These results suggest that low levels of thyroid homeostasis indexes may be associated with overall obesity in SCH, rather than central adiposity.
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Based on the official data modeling, this paper studies the transmission process of the Corona Virus Disease 2019 (COVID-19). The error between the model and the official data curve is quite small. At the same time, it realized forward prediction and backward inference of the epidemic situation, and the relevant analysis help relevant countries to make decisions.
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OBJECTIVE: Osteoporosis has become an important public health problem in China, especially among elderly postmenopausal women. Massive amounts of medical and health resources have been devoted to patients with osteoporosis and osteoporosis-related fractures. This study estimated the cost-effectiveness of alendronate, zoledronate, raloxifene, teriparatide, and calcium/vitamin D as treatments for osteoporosis in elderly postmenopausal women in China from the medical system perspective. METHODS: A Markov model was constructed by using TreeAge Pro 2015 software. This model simulated the disease process over 40 years in response to the five investigated therapeutic strategies. Each cycle lasted for 1 year. The model parameters included Chinese epidemiological data, clinical effectiveness, cost, and utility. Total treatment costs and quality-adjusted life-years (QALYs) were estimated, and incremental cost-effectiveness analysis was performed. Univariate and probabilistic sensitivity analyses were conducted to verify the model. RESULTS: The calcium/vitamin D strategy, zoledronate, alendronate, teriparatide, and raloxifene offered patients 10.24, 10.83, 10.70, 10.88, and 10.54 QALYs at the cost of $3,799.72, $8,425.61, $9,849.89, $34,843.72, and $13,353.33 for over 40 years, respectively. The alendronate and raloxifene strategies were eliminated because they were less effective and more expensive than the other strategies. The base-case analysis revealed that the incremental cost-effectiveness ratios (ICERs) of the zoledronate strategy relative to those of the calcium/vitamin D strategy were $7,864.59/QALY. This result indicated that the zoledronate strategy was more cost-effective than other strategies and was within the willingness-to-pay threshold of China ($28,624/QALY). The ICERs of the teriparatide versus zoledronate strategies were $4,70,797.08/QALY, which exceeded the threshold. CONCLUSION: From the perspective of the Chinese medical system, zoledronate is more cost-effective than the calcium/vitamin D strategy, alendronate, raloxifene, and teriparatide for the treatment of osteoporosis in elderly postmenopausal women. Not factoring the parameters of adherence and persistence in, and consequent variability in treatment effectiveness relative risks, seems like a major limitation, but it can be speculated that it would not change the conclusion that zoledronate is the most economical strategy.
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Conservadores de la Densidad Ósea/economía , Osteoporosis Posmenopáusica/tratamiento farmacológico , Anciano , Anciano de 80 o más Años , Conservadores de la Densidad Ósea/uso terapéutico , China , Análisis Costo-Beneficio , Femenino , Humanos , Cadenas de Markov , Persona de Mediana Edad , Osteoporosis Posmenopáusica/economía , Fracturas Osteoporóticas/prevención & control , Medición de RiesgoRESUMEN
For point-of-care applications, integrating sensors into a microfluidic chip is a nontrivial task because conventional detection modules are bulky and microfluidic chips are small in size and their fabrication processes are not compatible. In this work, a solid-state microfluidic chip with on-chip acoustic sensors using standard thin-film technologies is introduced. The integrated chip is essentially a stack of thin films on silicon substrate, featuring compact size, electrical input (fluid control), and electrical output (sensor read-out). These features all contribute to portability. In addition, by virtue of processing discrete microdroplets, the chip provides a solution to the performance degradation bottleneck of acoustic sensors in liquid-phase sensing. Label-free immunoassays in serum are carried out, and the viability of the chip is further demonstrated by result comparison with commercial ELISA in prostate-specific antigen sensing experiments. The solid-state chip is believed to fit specific applications in personalized diagnostics and other relevant clinical settings where instrument portability matters.
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Acústica , Microfluídica/métodos , Animales , Anticuerpos/química , Anticuerpos/inmunología , Técnicas Biosensibles/métodos , Fluoresceína-5-Isotiocianato/química , Humanos , Inmunoensayo , Dispositivos Laboratorio en un Chip , Microfluídica/instrumentación , Antígeno Prostático Específico/análisis , Antígeno Prostático Específico/inmunología , ConejosRESUMEN
Although previous studies have reported the protective effect of glucagon-like peptide-1 (GLP-1) in diabetes nephropathy, the molecular mechanism such as nephroprotection remains elusive. In this study, we explored the molecular mechanism of exendin-4 as an GLP-1 receptor agonist for the treatment of tert-butyl hydroperoxide (t-BHP)-induced injury in mouse glomerulus mesangial cells (SV40 MES 13 cells) via an NMR-based metabonomic analysis. We found that exendin-4 protected mesangial cells from t-BHP-mediated toxicity, decreased the percentage of t-BHP-treated cells undergoing apoptosis, and restored glucose consumption in the t-BHP-treated group. A supervised partial least-squares discriminant analysis (PLS-DA) revealed that the metabolic profiles could be distinguished between the control, t-BHP-treated, and exendin-4-pretreated groups. Our findings indicate that exendin-4 pretreatment can cause distinct changes in energy, glycerol phospholipid, and amino acid metabolism. Our study provides novel insight into the metabolic mechanism of exendin-4-mediated nephroprotective effects.
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Hipoglucemiantes/farmacología , Células Mesangiales/efectos de los fármacos , Péptidos/farmacología , Sustancias Protectoras/farmacología , Ponzoñas/farmacología , terc-Butilhidroperóxido/antagonistas & inhibidores , Aminoácidos/metabolismo , Animales , Apoptosis/efectos de los fármacos , Línea Celular , Proliferación Celular/efectos de los fármacos , Metabolismo Energético/efectos de los fármacos , Exenatida , Glucosa/metabolismo , Glicerofosfolípidos/metabolismo , Espectroscopía de Resonancia Magnética , Células Mesangiales/citología , Células Mesangiales/metabolismo , Metabolómica/métodos , Ratones , Oxidantes/antagonistas & inhibidores , Oxidantes/farmacología , Análisis de Componente Principal , terc-Butilhidroperóxido/farmacologíaRESUMEN
Micro/nano scale biosensors integrated with the local adsorption mask have been demonstrated to have a better limit of detection (LOD) and less sample consumptions. However, the molecular diffusions and binding kinetics in such confined droplet have been less studied which limited further development and application of the local adsorption method and imposed restrictions on discovery of new signal amplification strategies. In this work, we studied the kinetic issues via experimental investigations and theoretical analysis on microfabricated biosensors. Mass sensitive film bulk acoustic resonator (FBAR) sensors with hydrophobic Teflon film covering the non-sensing area as the mask were introduced. The fabricated masking sensors were characterized with physical adsorption of bovine serum albumin (BSA) and specific binding of antibody and antigen. Over an order of magnitude improvement on LOD was experimentally monitored. An analytical model was introduced to discuss the target molecule diffusion and binding kinetics in droplet environment, especially the crucial effects of incubation time, which has been less covered in previous local adsorption related literatures. An incubation time accumulated signal amplification effect was theoretically predicted, experimentally monitored and carefully explained. In addition, device optimization was explored based on the analytical model to fully utilize the merits of local adsorption. The discussions on the kinetic issues are believed to have wide implications for other types of micro/nano fabricated biosensors with potentially improved LOD.