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1.
Cardiovasc Drugs Ther ; 37(5): 905-916, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-35467312

RESUMO

PURPOSE: To assess the cost-effectiveness of evolocumab, a PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitor, compared with ezetimibe, both added to background statin therapy in patients with recent acute coronary syndrome (ACS) events (in the past 12 months) and low-density lipoprotein cholesterol (LDL-C) levels ≥ 100 mg/dL in China. METHODS: A health economic evaluation was performed from a Chinese healthcare perspective, using a Markov model over a lifetime horizon based on a baseline cardiovascular (CV) event rate from claims database data and efficacy from the FOURIER trial. The health benefit was reflected in the decrease of LDL-C level, which led to a decrease of cardiovascular events. The costs of cardiovascular events and the utility value of each health state were derived from the published literature. Sensitivity analyses were conducted to evaluate the effects of uncertainty in parameters and the robustness of the model. The cost-effectiveness of evolocumab was also explored in patients with recent myocardial infarction (MI), at very high risk (VHR) of atherosclerotic cardiovascular disease (ASCVD), and homozygous familiar hypercholesterolemia (HoFH). RESULTS: In patients with recent ACS, evolocumab was associated with incremental quality-adjusted life-years (QALYs) of 1.33 and incremental costs of 115,782 yuan versus ezetimibe, both with background statin therapy, resulting in an incremental cost-effectiveness ratio (ICER) of 87,050 yuan per QALY gained. The probability of evolocumab + statins being cost-effective at a threshold of 217,341 yuan (three times per capita GDP, 2020), compared with ezetimibe + statins, was 100% in patients with recent ACS, recent MI, VHR ASCVD, and HoFH. CONCLUSION: Compared with ezetimibe + statins, the combination of evolocumab + statins was found to be cost-effective at a threshold of 217,341 yuan (three times per capita GDP, 2020) in patients with recent ACS events in China.


Assuntos
Síndrome Coronariana Aguda , Anticolesterolemiantes , Aterosclerose , Doenças Cardiovasculares , Hipercolesterolemia Familiar Homozigota , Inibidores de Hidroximetilglutaril-CoA Redutases , Humanos , Síndrome Coronariana Aguda/diagnóstico , Síndrome Coronariana Aguda/tratamento farmacológico , Anticolesterolemiantes/efeitos adversos , LDL-Colesterol , Análise Custo-Benefício , Análise de Custo-Efetividade , Ezetimiba/uso terapêutico , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Pró-Proteína Convertase 9
2.
Chem Soc Rev ; 51(15): 6574-6651, 2022 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-35815699

RESUMO

Significant progress has been made in direct air capture (DAC) in recent years. Evidence suggests that the large-scale deployment of DAC by adsorption would be technically feasible for gigatons of CO2 capture annually. However, great efforts in adsorption-based DAC technologies are still required. This review provides an exhaustive description of materials development, adsorbent shaping, in situ characterization, adsorption mechanism simulation, process design, system integration, and techno-economic analysis of adsorption-based DAC over the past five years; and in terms of adsorbent development, affordable DAC adsorbents such as amine-containing porous materials with large CO2 adsorption capacities, fast kinetics, high selectivity, and long-term stability under ultra-low CO2 concentration and humid conditions. It is also critically important to develop efficient DAC adsorptive processes. Research and development in structured adsorbents that operate at low-temperature with excellent CO2 adsorption capacities and kinetics, novel gas-solid contactors with low heat and mass transfer resistances, and energy-efficient regeneration methods using heat, vacuum, and steam purge is needed to commercialize adsorption-based DAC. The synergy between DAC and carbon capture technologies for point sources can help in mitigating climate change effects in the long-term. Further investigations into DAC applications in the aviation, agriculture, energy, and chemical industries are required as well. This work benefits researchers concerned about global energy and environmental issues, and delivers perspective views for further deployment of negative-emission technologies.


Assuntos
Aminas , Dióxido de Carbono , Adsorção , Aminas/química , Dióxido de Carbono/química , Cinética , Porosidade
3.
Int Wound J ; 20(6): 2483-2491, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36717766

RESUMO

We conducted a meta-analysis to assess the diagnostic performance of chest ultrasound compared with a pericardial window for the detection of occult penetrating cardiac wounds in patients with penetrating thoracic trauma who were hemodynamically stable. A systematic literature search up to December 2022 was performed and 567 related studies were evaluated. The chosen studies comprised 629 penetrating thoracic trauma subjects who participated in the selected studies' baseline. Odds ratio (OR) with 95% confidence intervals (CIs) were calculated to assess the effect of different chest ultrasounds on wound infection after penetrating thoracic trauma by the dichotomous methods with a random or fixed effect model. The chest ultrasound resulted in significantly lower occult penetrating cardiac wounds detection (OR, 0.02; 95% CI, 0.01-0.08, P < 0.001), higher false positive (OR, 33.85; 95% CI, 9.21-124.39, P < 0.001), and higher false negative (OR, 27.31; 95% CI, 7.62-97.86, P < 0.001) compared with the pericardial window in penetrating thoracic trauma. The chest ultrasound resulted in significantly lower occult penetrating cardiac wound detection, higher false positives, and higher false negatives compared with the pericardial window in penetrating thoracic trauma. Although care should be taken when dealing with the results because all of the studies had less than 200 subjects as a sample size.


Assuntos
Traumatismos Torácicos , Ferimentos Penetrantes , Humanos , Técnicas de Janela Pericárdica , Traumatismos Torácicos/diagnóstico por imagem , Ultrassonografia , Ferimentos Penetrantes/diagnóstico por imagem
4.
Clin Proteomics ; 18(1): 32, 2021 Dec 29.
Artigo em Inglês | MEDLINE | ID: mdl-34963468

RESUMO

BACKGROUND: Type 2 diabetic kidney disease is the most common cause of chronic kidney diseases (CKD) and end-stage renal diseases (ESRD). Although kidney biopsy is considered as the 'gold standard' for diabetic kidney disease (DKD) diagnosis, it is an invasive procedure, and the diagnosis can be influenced by sampling bias and personal judgement. It is desirable to establish a non-invasive procedure that can complement kidney biopsy in diagnosis and tracking the DKD progress. METHODS: In this cross-sectional study, we collected 252 urine samples, including 134 uncomplicated diabetes, 65 DKD, 40 CKD without diabetes and 13 follow-up diabetic samples, and analyzed the urine proteomes with liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). We built logistic regression models to distinguish uncomplicated diabetes, DKD and other CKDs. RESULTS: We quantified 559 ± 202 gene products (GPs) (Mean ± SD) on a single sample and 2946 GPs in total. Based on logistic regression models, DKD patients could be differentiated from the uncomplicated diabetic patients with 2 urinary proteins (AUC = 0.928), and the stage 3 (DKD3) and stage 4 (DKD4) DKD patients with 3 urinary proteins (AUC = 0.949). These results were validated in an independent dataset. Finally, a 4-protein classifier identified putative pre-DKD3 patients, who showed DKD3 proteomic features but were not diagnosed by clinical standards. Follow-up studies on 11 patients indicated that 2 putative pre-DKD patients have progressed to DKD3. CONCLUSIONS: Our study demonstrated the potential for urinary proteomics as a noninvasive method for DKD diagnosis and identifying high-risk patients for progression monitoring.

5.
Memory ; 23(2): 254-67, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25625289

RESUMO

Results from three studies indicated that emotional responses to memories can be changed by altering the working self. In particular, these results showed that emotional reactions to memories: (1) were especially positive when memories were perceived to be central to the working self (Experiment 1); (2) were muted when the working self was changed by adopting a third-person perspective during recall (Experiment 1); (3) of an event in the life of each participant's mother weakened when an individual was induced to experience a self that felt less close to their mother (Experiment 2) and (4) of a childhood event provoked especially positive emotional reactions after exposure to a mortality salience manipulation that increased perceived self-worth (Experiment 3). The extent to which mother was included in the self (Experiment 2) and self-worth (Experiment 3) plausibly mediated the effects of the manipulations on participants' emotional reactions to recalled events.


Assuntos
Ego , Emoções , Memória Episódica , Rememoração Mental , Adolescente , Feminino , Humanos , Masculino , Autoimagem , Adulto Jovem
6.
Behav Brain Sci ; 37(1): 104-5, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24572246

RESUMO

Social influence and payoff transparency interact with each other to influence decision making. Social influence masks payoff transparency, and lacking transparency drives people to seek social influence. Moreover, our survey supports our claim by showing that social influence and payoff transparency correlate with each other (r(53) = -.71). Bentley et al.'s model can be revised to accommodate the covariance.


Assuntos
Coleta de Dados , Tomada de Decisões , Comportamento Social , Rede Social , Humanos
7.
J Food Sci ; 89(6): 3455-3468, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38700315

RESUMO

Excessive accumulation of advanced glycation end products (AGEs) in the body is associated with diabetes and its complications. In this study, we aimed to explore the potential and mechanism of coffee leaf extract (CLE) in inhibiting the generation of AGEs and their precursors in an in vitro glycation model using bovine serum albumin and glucose (BSA-Glu) for the first time. High-performance liquid chromatography analysis revealed that CLE prepared with ultrasound pretreatment (CLE-U) contained higher levels of trigonelline, mangiferin, 3,5-dicaffeoylquinic acid, and γ-aminobutyric acid than CLE without ultrasound pretreatment (CLE-NU). The concentrations of these components, along with caffeine and rutin, were dramatically decreased when CLE-U or CLE-NU was incubated with BSA-Glu reaction mixture. Both CLE-U and CLE-NU exhibited a dose-dependent inhibition of fluorescent AGEs, carboxymethyllysine, fructosamine, 5-hydroxymethylfurfural, 3-deoxyglucosone, glyoxal, as well as protein oxidation products. Notably, CLE-U exhibited a higher inhibitory capacity compared to CLE-NU. CLE-U effectively quenched fluorescence intensity and increased the α-helix structure of the BSA-Glu complex. Molecular docking results suggested that the key bioactive compounds present in CLE-U interacted with the arginine residues of BSA, thereby preventing its glycation. Overall, this research sheds light on the possible application of CLE as a functional ingredient in combating diabetes by inhibiting the generation of AGEs.


Assuntos
Produtos Finais de Glicação Avançada , Extratos Vegetais , Folhas de Planta , Soroalbumina Bovina , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Folhas de Planta/química , Soroalbumina Bovina/química , Coffea/química , Alcaloides/farmacologia , Furaldeído/análogos & derivados , Furaldeído/farmacologia , Frutosamina , Cromatografia Líquida de Alta Pressão , Glioxal , Glucose/metabolismo , Simulação de Acoplamento Molecular , Glicosilação/efeitos dos fármacos , Ácido Quínico/análogos & derivados , Ácido Quínico/farmacologia , Rutina/farmacologia , Lisina/análogos & derivados , Cafeína/farmacologia , Desoxiglucose/análogos & derivados , Desoxiglucose/farmacologia , Xantonas
8.
Sci Total Environ ; 945: 174086, 2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-38908591

RESUMO

Aerosol proteins, as core biological components of bioaerosols, are garnering increasing attention due to their environmental significance, including their roles in atmospheric processes and associated health risks. However, observational data on the proteins are very limited, leaving their distribution and variation in the atmosphere poorly understood. To investigate the long-distance transport of proteins with Asian dust in the Northern Hemisphere middle latitude westerlies to remote downwind areas, we quantified the soluble proteins in aerosol particles, referred to as aerosol soluble proteins (ASPs), collected in the coastal city of Kumamoto, Japan, during the spring of 2023, when three dust events occurred. The concentration of ASPs ranged from 0.22 to 1.68 µg m-3, with an average concentration of 0.73 ± 0.36 µg m-3 under dust conditions and 0.31 ± 0.05 µg m-3 under non-dust conditions. During the dust periods, the largest concentration of ASPs (1.68 µg m-3) coincided with the peak concentration of suspended particulate matter, and the concentration strongly correlated with the mass concentration of particles larger than 2.5 µm, indicating a close dependence of ASPs on dust particles. Primary estimations indicated a dry deposition flux of ASPs at approximately 1.10 ± 0.87 mg m-2 d-1 under the dust conditions. These results prove that Asian dust efficiently transports proteins, facilitating their dispersion in the atmosphere.


Assuntos
Aerossóis , Poluentes Atmosféricos , Poeira , Monitoramento Ambiental , Poeira/análise , Japão , Aerossóis/análise , Poluentes Atmosféricos/análise , Proteínas/análise , Material Particulado/análise , Atmosfera/química
9.
Mol Nutr Food Res ; 68(6): e2300706, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38419398

RESUMO

As an important nutritional component, vitamin C (Vc) shows good antitumor activity in a variety of cancer, but there are few studies in pulmonary metastasis. In order to verify its anticancer and antimetastatic effect, the study sets up H22 pulmonary metastasis mouse model. The results show that intraperitoneal injection of Vc inhibits pulmonary metastasis through up-regulating the expression of Nrf2, HO-1, cleaved caspases 3 and 9, and causing DNA damage and apoptosis which is similar to the pro-oxidant effect of Vc in p53 null cells (H1299 cells). Meanwhile, oral administration of Vc up-regulates the expression of p53, directly activates Nrf2/HO-1 pathway, increases expression of cleaved caspases 3 and 9, and ultimately inhibits pulmonary metastasis, which is the same as the antioxidant result of Vc in p53 wild-type cells. In addition, Vc inhibits the proliferation and migration of lung cancer cells in a concentration-dependent manner and has little cytotoxic effects on normal cells. Notably, the experiment further illustrates that besides intravenous Vc, oral Vc significantly inhibits the pulmonary metastasis in mice. All in all, these findings provide new clues for Vc-treated pulmonary metastasis in clinical research.


Assuntos
Ácido Ascórbico , Neoplasias Pulmonares , Animais , Camundongos , Ácido Ascórbico/farmacologia , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Estresse Oxidativo , Vitaminas/farmacologia , Caspases/metabolismo
10.
Sci Total Environ ; 916: 170316, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38278236

RESUMO

Aerosol particles in two size ranges, namely 0.18-1.4 µm (fine) and larger than 1.4 µm (coarse), were collected in the pre-dust, in-dust, and post-dust air during the passage of a slowly-moving dust event at a coastal site in southwestern Japan. We identified the composition and size of individual particles using a scanning electron microscope to investigate the variations during dust passage. The particles could be classified as mineral-seasalt mixtures, non-mixture minerals, sulfur-containing minerals, and seasalt particles, and the number fractions of these type particles in the two size ranges exhibited significant variation across the three periods. In the coarse size range, mixture particles accounted for 17.6 %, 26.8 %, and 37.8 % of the particles in the pre-dust, in-dust, and post-dust air, respectively. Non-mixture particles made up 36.8 %, 29.2 %, and 24.3 % in the same respective periods. In the in-dust air, the average relative ratio of sulfur content in sulfur-containing mineral particles in the coarse range was 5.5 %, whereas in the fine range, it was 17.2 %. The aging state of sea salt components, described by the Cl loss and reflecting the changes in particles due to chemical reactions, exhibited significant differences in the two size ranges. In the fine range, the aging of >90 % particles was predominantly influenced by sulfate formation in the in-dust air. In contrast, nitrate likely played a certain role in both the pre-dust and post-dust air. In the coarse range, the aging was independent of sulfate formation. These results indicate the close dependence of the aging of dust particles on their size and the notable variations of the aged states, underscoring the essentiality to treat dust particles properly according to time and space for a better understanding on their roles in the marine atmosphere.

11.
Int J Biol Macromol ; 275(Pt 1): 133582, 2024 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-38955301

RESUMO

Inulin as a natural polysaccharide regulates intestinal microorganisms, and improves the immune and gastrointestinal function. In order to explore the effect of inulin on pulmonary metastasis of colon cancer, we set up a CT26 injected pulmonary metastatic model. The results showed that inulin used alone did not improve pulmonary metastasis of colon cancer, while inulin combined with rifaximin significantly prolonged the survival time of mice, and inhibited pulmonary metastasis compared with model and inulin groups. Inulin treatment increased the abundance of harmful bacteria such as Proteobacteria and Actinobacteria, while combined treatment decreased their abundance and increased the abundance of beneficial bacteria containing Firmicutes and Eubacterium which belonged to the bile acid-related bacteria. The combination treatment decreased the content of primary bile acids and secondary bile acids in the feces of mice, especial for DCA and LCA which were the agonists of TGR5. Furthermore, the combination treatment reduced the mRNA expression of the TGR5, cyclin dependent kinase 4, cyclin 1 and CDK2, increased the mRNA expression of p21 in the lung, down-regulated the level of NF-κB p65, and up-regulated the level of TNF-α compared with the model group. The above may be the reason for the better use of the combination treatment.

12.
Sci Total Environ ; 926: 171948, 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38527545

RESUMO

The exponential growth of the global population has resulted in a significant surge in the demand for food worldwide. Additionally, the impact of climate change has exacerbated crop losses caused by pests and pathogens. The transportation and utilization of traditional agrochemicals in the soil are highly inefficient, resulting in significant environmental losses and causing severe pollution of both the soil and aquatic ecosystems. Nanotechnology is an emerging field with significant potential for market applications. Among metal-based nanomaterials, copper-based nanomaterials have demonstrated remarkable potential in agriculture, which are anticipated to offer a promising alternative approach for enhancing crop yields and managing diseases, among other benefits. This review firstly performed co-occurrence and clustering analyses of previous studies on copper-based nanomaterials used in agriculture. Then a comprehensive review of the applications of copper-based nanomaterials in agricultural production was summarized. These applications primarily involved in nano-fertilizers, nano-regulators, nano-stimulants, and nano-pesticides for enhancing crop yields, improving crop resistance, promoting crop seed germination, and controlling crop diseases. Besides, the paper concluded the potential impact of copper-based nanomaterials on the soil micro-environment, including soil physicochemical properties, enzyme activities, and microbial communities. Additionally, the potential mechanisms were proposed underlying the interactions between copper-based nanomaterials, pathogenic microorganisms, and crops. Furthermore, the review summarized the factors affecting the application of copper-based nanomaterials, and highlighted the advantages and limitations of employing copper-based nanomaterials in agriculture. Finally, insights into the future research directions of nano-agriculture were put forward. The purpose of this review is to encourage more researches and applications of copper-based nanomaterials in agriculture, offering a novel and sustainable strategy for agricultural development.


Assuntos
Cobre , Praguicidas , Cobre/análise , Ecossistema , Agricultura/métodos , Praguicidas/análise , Nanotecnologia/métodos , Fertilizantes/análise , Solo
13.
J Agric Food Chem ; 72(18): 10366-10375, 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38651967

RESUMO

Intestinal stem cells (ISCs) sustain epithelial renewal by dynamically altering behaviors of proliferation and differentiation in response to various nutrition and stress inputs. However, how ISCs integrate bioactive substance morin cues to protect against heat-stable enterotoxin b (STb) produced by Escherichia coli remains an uncertain question with implications for treating bacterial diarrhea. Our recent work showed that oral mulberry leaf-derived morin improved the growth performance in STb-challenged mice. Furthermore, morin supplementation reinstated the impaired small-intestinal epithelial structure and barrier function by stimulating ISC proliferation and differentiation as well as supporting intestinal organoid expansion ex vivo. Importantly, the Wnt/ß-catenin pathway, an ISC fate commitment signal, was reactivated by morin to restore the jejunal crypt-villus architecture in response to STb stimulation. Mechanically, the extracellular morin-initiated ß-catenin axis is dependent or partially dependent on the Wnt membrane receptor Frizzled7 (FZD7). Our data reveal an unexpected role of leaf-derived morin, which represents molecular signaling targeting the FZD7 platform instrumental for controlling ISC regeneration upon STb injury.


Assuntos
Antioxidantes , Toxinas Bacterianas , Enterotoxinas , Infecções por Escherichia coli , Proteínas de Escherichia coli , Jejuno , Morus , Extratos Vegetais , Camundongos , Morus/química , Folhas de Planta/química , Via de Sinalização Wnt , Células-Tronco/efeitos dos fármacos , Células-Tronco/microbiologia , Células-Tronco/patologia , Proteínas de Escherichia coli/metabolismo , Técnicas In Vitro , Extratos Vegetais/farmacologia , Jejuno/efeitos dos fármacos , Jejuno/metabolismo , Jejuno/microbiologia , Jejuno/patologia , Regeneração , Toxinas Bacterianas/isolamento & purificação , Enterotoxinas/isolamento & purificação , Infecções por Escherichia coli/tratamento farmacológico , Antioxidantes/farmacologia
14.
Chin J Integr Med ; 30(3): 195-202, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38374490

RESUMO

OBJECTIVE: To evaluate the effect and safety of foot baths with Tangbi Waixi Decoction (TW) in treating patients with diabetic peripheral neuropathy (DPN). METHODS: It is a multicenter double-blinded randomized controlled trial. Participants with DPN were recruited between November 18, 2016 and May 30, 2018 from 8 hospitals in China. All patients received basic treatments for glycemic management. Patients received foot baths with TW herbal granules either 66.9 g (intervention group) or 6.69 g (control group) for 30 min once a day for 2 weeks and followed by a 2-week rest, as a therapeutic course. If the Toronto Clinical Scoring System total score (TCSS-TS) ⩾6 points, the patients received a total of 3 therapeutic courses (for 12 weeks) and were followed up for 12 weeks. The primary outcome was change in TCSS-TS score at 12 and 24 weeks. Secondary outcomes included changes in bilateral motor nerve conduction velocity (MNCV) and sensory nerve conduction velocity (SNCV) of the median and common peroneal nerve. Safety was also assessed. RESULTS: Totally 632 patients were enrolled, and 317 and 315 were randomized to the intervention and control groups, respectively. After the 12-week intervention, patients in both groups showed significant declines in TCSSTS scores, and significant increases in MNCV and SNCV of the median and common peroneal nerves compared with pre-treatment (P<0.05). The reduction of TCSS-TS score at 12 weeks and the increase of SNCV of median nerve at 24 weeks in the control group were greater than those in the intervention group (P<0.05). The number of adverse events did not differ significantly between groups (P>0.05), and no serious adverse event was related with treatment. CONCLUSION: Treatment of TW foot baths was safe and significantly benefitted patients with DPN. A low dose of TW appeared to be more effective than a high dose. (Registry No. ChiCTR-IOR-16009331).


Assuntos
Diabetes Mellitus , Neuropatias Diabéticas , Plantas Medicinais , Humanos , Neuropatias Diabéticas/tratamento farmacológico , Banhos , Método Duplo-Cego , Extratos Vegetais/uso terapêutico
15.
J Org Chem ; 78(7): 3243-9, 2013 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-23464705

RESUMO

In the addition of TMEDA in toluene, aryl Grignards could effectively and site-specifically ortho-arylate electron-deficient heteroarenes under mild conditions. This endeavor successfully changed the old low-yielding reaction, aryl Grignard addition to N-heteroarenes, into an efficient procedure for heterobiaryls. The combination of the inexpensive aryl Grignards, TMEDA, the cost-free air, no use of any transition-metal catalyst, the mild reaction conditions, and the high-yielding gram-scale results enables this new procedure to be cost-effective and potentially utilizable in industry.


Assuntos
Etilenodiaminas/química , Compostos Heterocíclicos/química , Compostos Organometálicos/química , Piridinas/química , Quinolinas/química , Quinoxalinas/síntese química , Elétrons , Estrutura Molecular , Quinoxalinas/química , Tolueno/química
16.
Adv Ther ; 40(2): 489-503, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36371480

RESUMO

INTRODUCTION: To assess the cost-effectiveness of evolocumab with statins versus placebo combined with statins in the treatment of adult patients with atherosclerotic cardiovascular disease (ASCVD) and low-density lipoprotein cholesterol (LDL-C) levels > 70 mg/dl after the maximum tolerable dose of statin therapy in China. METHODS: A Markov model, based on data from the FOURIER trial, claims databases, and published literature, was used to compare the health outcomes of the two therapies from the perspective of Chinese healthcare system. The time horizon in the model was a lifetime, the cycle length was a year, and the discount rate was 5%. The output indicators of the model included direct medical costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs). Sensitivity analyses were conducted on critical parameters such as cost, utility, and incidence of cardiovascular events to evaluate the effect of uncertainty in parameters and the robustness of the model. RESULTS: In Chinese adult patients with ASCVD and LDL-C levels > 70 mg/dl, evolocumab was associated with incremental QALYs of 1.25 and incremental costs of 18,714 CNY versus placebo, both with a statin therapy, resulting in an ICER of 14,969 CNY/QALY gained, which was less than the willingness to pay (WTP) threshold (80,976 CNY/QALY, a capita GDP of China, 2021). The result of one-way sensitivity analysis indicated that when the effect of evolocumab on myocardial infarction (MI) rate after the first year varied, ICER changed the most. The results of probabilistic sensitivity analysis showed that the probability of evolocumab added to statins being cost-effective at a threshold of 80,976 CNY/QALY was 100%. CONCLUSION: Compared with placebo and statin therapy combination, evolocumab added to statin therapy for adult patients with ASCVD and LDL-C > 70 mg/dl in China is cost-effective.


Assuntos
Aterosclerose , Doenças Cardiovasculares , Inibidores de Hidroximetilglutaril-CoA Redutases , Humanos , Adulto , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Análise Custo-Benefício , LDL-Colesterol , Doenças Cardiovasculares/tratamento farmacológico , População do Leste Asiático , Aterosclerose/tratamento farmacológico , Atenção à Saúde , Anos de Vida Ajustados por Qualidade de Vida
17.
Patient Prefer Adherence ; 17: 591-604, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36919186

RESUMO

Background: In China, bypassing is becoming increasingly prevalent. Such behavior, as going directly to upper-level health-care facilities without a primary care provider (PCP) referral when facing non-critical diseases, contrasts to "expanding the role of PCPs as the first-contact of care", may cause unneglectable damage to the healthcare system and people's physical health. Objective: To examine the relationship between patient experience in primary health-care clinics (PHCs) and their bypass behavior. Methods: A cross-sectional study was designed for data collection. From July 2021 to August 2021, we conducted a questionnaire survey nationally. Fifty-three investigators were dispatched to 212 pre-chosen PHCs, around which 1060 interviewees were selected to gather information, using a convenience sampling. The primary independent variable was scores measured by Chinese Primary Care Assessment Tool (PCAT-C) to quantify patients' experience at PHCs. The dependent variable was a binary variable measured by a self-developed instrument to identify whether participants actually practiced bypassing. Covariates were well-screened determinants of patients' bypass behavior including socio-demographic factors, policy factors, and health-care suppliers. Binary logistic regression analysis was employed to evaluate the association of patients' experience with their bypass behavior. Findings: A total of 928 qualified questionnaires were obtained. The first contact dimension (OR 0.961 [95% CI 0.934 to 0.988], P = 0.005) and continuity dimension (OR 1.034 [95% CI 1.000 to 1.068], P = 0.047) of patients' experience were significantly associated with patients' bypass behavior (P < 0.05). In addition, age (OR 1.072, [95% CI 1.015-1.132], P = 0.013) and gender (OR 2.044, [95% CI 1.139-3.670], P = 0.017) also made a statistically significant difference. Conclusion: Enhancement in patient experience at PHCs may help reduce their bypass behavior. Specifically, efforts are needed to improve primary care accessibility and utilization. The positive correlation between bypassing rates and continuity scores may require more attention on strengthening PCPs' technical quality besides the quality of interpersonal interactions.

18.
Sci Total Environ ; 865: 161238, 2023 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-36586682

RESUMO

Size-differentiated concentration of bacterial aerosols is essential for investigating their dissemination via the atmosphere. In this study, the number size distribution of bacterial aerosols was measured at a coastal site in southwestern Japan (32.324°N, 129.993°E) using a size-segregated eight-stage (>11, 7.0-11, 4.7-7.0, 3.3-4.7, 2.1-3.3, 1.1-2.1, 0.65-1.1, and 0.43-0.65µm) sampler. The results showed that the distribution differed according to the source areas: terrestrial air, oceanic air, or a combination of the two. The distribution in the long-distance transported terrestrial air from the Asian continent was monomodal, with a peak of 3.3-4.7 µm. The distribution in local land breeze air was bimodal, with the peaks at 0.43-1.1 and 3.3-4.7 µm. A similar bimodal distribution was encountered when the local island air and long-distance transported terrestrial air mixed. In contrast, the size distribution did not show clear peaks in the air from either nearby or remote marine areas. According to the air mass backward trajectories, the further the distance the air moved in the 72 h before arriving at the site, the lower the concentration of total bacterial aerosols. The estimation of dry deposition fluxes of bacterial cells showed that the deposition was dominated by cells larger than 1.1 µm with a relative contribution from 70.5 % to 93.7 %, except for the local land breeze cases, where the contributions in the size ranges larger and smaller than 1.1 µm were similar. These results show the distinctive number size distributions and removal processes of bacterial aerosols in different types of air. In addition, they indicate that size-dependent characteristics of airborne bacteria should be considered when studying their activities and roles in the atmospheric environment.


Assuntos
Poluentes Atmosféricos , Aerossóis/análise , Poluentes Atmosféricos/análise , Atmosfera , Bactérias , Monitoramento Ambiental/métodos , Japão , Tamanho da Partícula , Material Particulado/análise
19.
Sci Total Environ ; 864: 161040, 2023 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-36572311

RESUMO

The dissemination of bioaerosols in the westerly wind from the Asian continent to the northwestern Pacific constantly links the land and marine ecosystems. Several observation campaigns targeting bioaerosols were conducted in the coastal city Qingdao of China (QD), at a coast site of Kumamoto in southwestern Japan (KM), and in the northwestern Pacific (NP) between 2014 and 2016. We compared the concentration of bioaerosols in the range of 1.1-7.0 µm obtained in those campaigns to investigate their variation in the westerly wind. The substantial influence of westerlies on bioaerosol concentration was confirmed in the three areas. In the case of non-dust air, the arrival of the continental air led to a 29 % decrease of bioaerosols at KM while a 57 % increase at NP, indicating that the concentration in non-dust air was lower than the local level in the island air while higher than that in the remote marine air. In case of dust occurrence, bioaerosols in the air decreased with the distance from the Asian continent at KM and NP consecutively, and the arrival of the air caused a 2-fold increase at KM and a 1.7-fold increase at NP. The relative concentration increase rate of bioaerosols (IRRC), defined as the ratio of the increment of bioaerosols caused by long-distance transported air to the local level in each area, decreased rapidly after the air left the continent in the dust cases, which is similar to the decrease of the dry deposition flux of dust reported in the literature. This result indicates that the reduction of bioaerosols in the dusty air was likely dominated by the removal of bioaerosols attached to dust particles.


Assuntos
Poluentes Atmosféricos , Humanos , Aerossóis/análise , Microbiologia do Ar , Poluentes Atmosféricos/análise , Poeira/análise , Ecossistema , Monitoramento Ambiental , Vento
20.
Biochim Biophys Acta Mol Cell Res ; 1870(3): 119431, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36632926

RESUMO

During heat stress (HS), the intestinal epithelium suffers damage due to imbalance of tissue homeostasis. However, the specific mechanism by which intestinal stem cells (ISCs) migrate and differentiate along the crypt-villus axis to heal lesions upon insult is unclear. In our study, C57BL/6 mice and IPEC-J2 cells were subjected to normal ambient conditions (25 °C for 7 days in vivo and 37 °C for 18 h in vitro) or 41 °C. The results showed that HS impaired intestinal morphology and barrier function. The numbers of ISCs (SOX9+ cells), mitotic cells (PCNA+ cells), and differentiated cells (Paneth cells marked by lysozyme, absorptive cells marked by Villin, goblet cells marked by Mucin2, enteroendocrine cells marked by Chromogranin A, and tuft cells marked by DCAMKL1) were reduced under high temperature. Importantly, BrdU incorporation confirmed the decreased migration ability of jejunal epithelial cells exposed to 41 °C. Furthermore, intestinal organoids (IOs) expanded from jejunal crypt cells in the HS group exhibited greater growth disadvantages. Mechanistically, the occurrence of these phenotypes was accompanied by FAK/paxillin/F-actin signaling disruption in the jejunum. The fact that the FAK agonist ZINC40099027 reversed the HS-triggered inhibition of IPEC-J2 cell differentiation and migration further confirmed the dominant role of FAK in response to high-temperature conditions. Overall, the present investigation is the first to reveal a major role of FAK/paxillin/F-actin signaling in HS-induced ISC migration and differentiation along the crypt-villus axis, which indicates a new therapeutic target for intestinal epithelial regeneration after heat injuries.


Assuntos
Actinas , Mucosa Intestinal , Animais , Camundongos , Actinas/metabolismo , Diferenciação Celular , Movimento Celular , Mucosa Intestinal/metabolismo , Camundongos Endogâmicos C57BL , Paxilina/metabolismo , Células-Tronco/metabolismo
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