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1.
Acc Chem Res ; 57(5): 795-813, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38394347

RESUMO

ConspectusThe selective functionalization/transformation of ubiquitous pyridine-fused N-heteroarenes is a practical method to synthesize structurally novel N-heterocycles, which is important for the development of medicines, bioactive agents, agrochemicals, materials, ligands, sensors, pigments, dyes, etc. However, owing to thermodynamic stability, kinetic inertness, and lone electron pair-induced catalyst deactivation of the pyridine-fused N-heteroarenes, limited strategies (e.g., C-H activation/functionalization, electrophilic substitution, and the Minisci reaction) are available to realize the synthetic purpose and maintain the aromaticity of the final products. Moreover, the relevant transformations have limitations such as needing harsh reaction conditions, requiring the preinstallation of specific coupling agents containing transformable functionalities or directing groups, using less environmentally benign oxidants and/or acidic activators, and poor selectivity. Herein, considering that imines, enamines, radicals, and cyclic amines are generated during the reduction of pyridine-fused N-heteroarenes, the precise transformation of these reductive intermediates offers a fundamental basis for developing novel tandem reactions. Our group revealed that a slow reduction rate, synergistic catalysis, and controlled electroreduction are effective strategies for fulfilling the selective reductive functionalization of pyridine-fused N-heteroarenes. Thus, we established a series of new synthetic methods that provide diverse construction modalities for functionalized N-heterocycles. The striking features of these synthetic methods include high efficiency, atom economy, and the use of readily accessible N-heteroarenes as transformable feedstocks in the absence of flammable and pressurized H2 gas, alongside a promising potential of the obtained N-heterocyclic products. The present study would be appealing to the fields of synthetic organic chemistry, catalysis, biomedical chemistry, and functional materials. This Account describes the application of reductive dearomatization as substrate-activating and tandem reaction-initiating modes and summarizes the reductive functionalization of pyridine-fused N-heteroarenes via selective alkylation, arylation, and annulation at nitrogen, α, ß, and other remote carbon sites achieved over the past 8 years. Details regarding the development of new reactions and their plausible mechanisms and perspectives are discussed. We hope our contributions to this field will aid in the further development of novel strategies for the functionalization/transformation of pyridine-fused N-heteroarenes and tackle the intractable challenges in this area.

2.
Int J Equity Health ; 22(1): 155, 2023 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-37582742

RESUMO

BACKGROUND: Turnover problems among primary health care workers are a significant contributor to the shortage of health human resources. This study aims to determine the relationship between job stress and turnover intention among primary health care workers, as well as to examine the mediating effects of job satisfaction and presenteeism on this relationship. METHODS: Stratified random sampling and quota sampling were used to select 703 primary health care workers in Jilin Province, China in January 2020. Validated scales were used to measure turnover intention, job stress, job satisfaction, and presenteeism among primary health care workers. The study utilized a partial least squares structural equation modeling (PLS-SEM) approach to test the research hypotheses. RESULTS: The turnover intention score of primary health care workers in Jilin Province was 2.15 ± 1.03, and 19.5% of respondents reported a higher turnover intention. Significant sex and occupation differences were found, with a higher rate of turnover intention for male and doctor groups among primary health care workers. This study also revealed a positive correlation between job stress and turnover intention (ß = 0.235, P < 0.001), a significant negative correlation between job satisfaction and turnover intention (ß= -0.347, P < 0.001), and a significant positive correlation between presenteeism and turnover intention (ß = 0.153, P < 0.001). Moreover, the study revealed a significant indirect effect of job stress on turnover intention which was mediated by job satisfaction (ß = 0.183, P < 0.001) and presenteeism (ß = 0.078, P < 0.001). CONCLUSION: We confirmed the positive association between job stress and presenteeism with turnover intention, as well as the negative association between job satisfaction and turnover intention. Moreover, our study confirmed the mediating role of job satisfaction and presenteeism in the relationship between job stress and turnover intention. This study provides scientific evidence to address the turnover problem among primary health care workers.


Assuntos
Satisfação no Emprego , Estresse Ocupacional , Humanos , Masculino , Intenção , Presenteísmo , Estudos Transversais , Reorganização de Recursos Humanos , China , Atenção Primária à Saúde , Inquéritos e Questionários
3.
Biomed Chromatogr ; 37(2): e5552, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36408991

RESUMO

A sensitive and reliable LC-MS/MS method is established and validated to determine the concentration of celecoxib, in the serum of cynomolgus monkey, using celecoxib-D7 as an internal standard. The pharmacokinetic process was investigated after giving Celebrex, celecoxib nanoparticles (CXB-NPs) and hyaluronic acid celecoxib nanoparticles (HA-CXB-NPs) by intragastric (i.g.) administration. Chromatographic separation was performed with a C18 column (2.1 × 100 mm, 2.6 µm) at 40°C with a mobile phase of 2‰ HCOOH in water and acetonitrile. The mass spectral acquisition was then performed in the multiple reaction monitoring mode, with negative ESI ion at m/z 380.0 → 316.0 and m/z 387.1 → 323.1 for celecoxib and celecoxib-D7, respectively. Good linearity was observed over the concentration range from 3 to 2,000 ng/ml (R2 = 0.9954). The intra- and inter-day precision and accuracy, matrix effect and extraction recovery, as well as stability, all met the determination requirements of biological samples. The pharmacokinetic parameters of Celebrex, CXB-NPs and HA-CXB-NPs were determined as: area under the curve, 1,855.98 ± 346.59, 1,908.00 ± 1,130.24 and 2,164.48 ± 657.47 h·ng/ml; peak concentration, 261.08 ± 113.26, 261.12 ± 94.67 and 263.34 ± 151.78 µg/L; time to peak concentration, 2.00 ± 1.22, 4.00 ± 0.00 and 3.60 ± 0.89 h; half-life, 4.39 ± 1.26, 2.33 ± 0.94 and 4.92 ± 3.13 h; relative bioavailability, 102.80 ± 49.62 and 116.63 ± 25.55%. The validated method was successfully applied to the pharmacokinetic study of celecoxib in cynomolgus monkey, after i.g. administration. The preparation of the nanoparticles of celecoxib and the modification of hyaluronic acid on the surface of nanoparticles could improve the bioavailability and prolong the circulation of celecoxib in vivo, which could lay the foundation for further development of celecoxib nanoparticles.


Assuntos
Nanopartículas , Espectrometria de Massas em Tandem , Animais , Celecoxib , Preparações Farmacêuticas , Cromatografia Líquida , Macaca fascicularis , Espectrometria de Massas em Tandem/métodos , Ácido Hialurônico , Cromatografia Líquida de Alta Pressão/métodos , Administração Oral , Reprodutibilidade dos Testes
4.
Int J Equity Health ; 21(1): 37, 2022 03 17.
Artigo em Inglês | MEDLINE | ID: mdl-35300695

RESUMO

BACKGROUND: The serious shortage of human resources for primary health care (PHC) is a common issue in health reforms worldwide. China has proposed that it is an effective way to encourage and guide qualified medical personnel to work in primary health care institutions (PHCIs). However, few studies have been conducted on the willingness and influencing factors of medical personnel to seek employment at PHCIs. METHODS: Based on implicit theory and lexical approach, pre-investigation was conducted to collect the items that influence the medical personnel to seek employment at PHCIs from the perspective of guided objects. Through a three-phase investigation of 1160 doctors in 29 public hospitals in 9 cities, the items were categorized, and a structural equation model was established and verified to explore the interrelationship of influencing factors. RESULTS: A total of 6 factors were rotated, including Sense of Gain (SG), Internal Organization Development (IOD), Remuneration and Development (RD), Condition of the City Where the PHCI Is Located (CCPL), Job Responsibilities (JR) and Family Support (FS). The results of the model showed that IOD, RD, JR and FS had a significantly positive effect on the SG. In addition, the FS, RD and JR significantly mediated the relationship between the internal and external environment of PHCIs and SG. The values of the fit index indicated an acceptable-fitting model. CONCLUSION: Family, remuneration, individual development, and job responsibility are closely related to the willingness of medical personnel to seek employment at PHCIs, and the internal and external environment of PHCIs is also an important factor. Therefore, the development of PHC providers can be promoted by paying attention to the family members of medical personnel, establishing a reasonable remuneration system, providing suitable development opportunities, arranging work rationally and improving the internal construction of PHCIs.


Assuntos
Emprego , Médicos , Hospitais Públicos , Humanos , Atenção Primária à Saúde , Recursos Humanos
5.
Artigo em Inglês | MEDLINE | ID: mdl-35831138

RESUMO

BACKGROUND: The shortage of health care workforce is a common problem all over the world and one of the main reasons for the shortage is the high turnover rate. Based on the characteristics of medical work, this study explored the relationship among public service motivation (PSM), work stress, task performance and turnover intention. METHODS: Medical personnel in public hospitals were selected by stratified random sampling in Jilin province of China and validated scales from previous studies were applied to measure the variables. Besides, a structural equation model of turnover intention was constructed to demonstrate the relationship. RESULTS: A total of 3191 valid questionnaires were collected. The results showed that the score of turnover intention was 2.02 ± 1.13. There are significant differences in turnover intention among medical staff of different genders and departments. At the same time, PSM had direct and negative effects on the turnover intention (ß = -0.292, P < 0.001), work stress had direct and positive effects on the turnover intention (ß = 0.479, P < 0.001), whereas task performance had no significant effect on turnover intention (ß = 0.044, P < 0.142). The results showed an acceptable fit model. CONCLUSION: The greater the PSM, the lower the turnover intention, and the higher the work stress, the higher the turnover intention. In addition, work stress and task performance play a mediating role between PSM and turnover intention. This paper provides theoretical support for the measures to reduce the turnover intention of medical staff.


Assuntos
Motivação , Estresse Ocupacional , China , Estudos Transversais , Feminino , Humanos , Intenção , Satisfação no Emprego , Masculino , Reorganização de Recursos Humanos , Inquéritos e Questionários , Análise e Desempenho de Tarefas
6.
J Org Chem ; 85(8): 5629-5637, 2020 04 17.
Artigo em Inglês | MEDLINE | ID: mdl-32203658

RESUMO

Herein, a new iodide-mediated three-component annulation reaction of secondary anilines, cyclohexanones, and elemental sulfur is demonstrated, which allows access to various phenothiazines with the merits of formation of multiple chemical bonds in one single operation, high step and atom efficiency, readily available feedstocks and catalyst system, and good substrate and functional group compatibility. The developed chemistry capable of constructing novel phenothiazines with structural diversity offers a significant basis for further applications.

7.
J Am Chem Soc ; 141(14): 5640-5644, 2019 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-30912936

RESUMO

Sodium superionic conductors are keys to develop high safety and low cost all-solid-state sodium batteries. Among developed sodium ionic conductors, antiperovskite-type ionic conductors have attracted vast interest due to their high structural tolerance and good formability. Herein, we successfully synthesize Na3OBH4 with cubic antiperovskite structure by solid-state reaction from Na2O and NaBH4. Na3OBH4 exhibits ionic conductivity of 4.4 × 10-3 S cm-1 at room temperature (1.1 × 10-2 S cm-1 at 328 K) and activation energy of 0.25 eV. The ionic conductivity is 4 orders of magnitude higher than the existing antiperovskite Na3OX (X = Cl, Br, I). It is shown that such enhancement is not only due to the specific cubic antiperovskite structure of Na3OBH4 but also because of the rotation of BH4 cluster anion. This work deepens the understanding of the antiperovskite structure and the role of cluster anions for superionic conduction.

8.
Mol Cancer ; 17(1): 5, 2018 01 11.
Artigo em Inglês | MEDLINE | ID: mdl-29325547

RESUMO

BACKGROUND: The communication between carcinoma associated fibroblasts (CAFs) and cancer cells facilitate tumor metastasis. In this study, we further underlying the epigenetic mechanisms of CAFs feed the cancer cells and the molecular mediators involved in these processes. METHODS: MCF-7 and MDA-MB-231 cells were treated with CAFs culture conditioned medium, respectively. Cytokine antibody array, enzyme-linked immunosorbent assay, western blotting and immunofluorescence were used to identify the key chemokines. Chromatin immunoprecipitation and luciferase reporter assay were performed to explore the transactivation of target LncRNA by CAFs. A series of in vitro assays was performed with RNAi-mediated knockdown to elucidate the function of LncRNA. An orthotopic mouse model of MDA-MB-231 was conducted to confirm the mechanism in vivo. RESULTS: Here we reported that TGF-ß1 was top one highest level of cytokine secreted by CAFs as revealed by cytokine antibody array. Paracrine TGF-ß1 was essential for CAFs induced EMT and metastasis in breast cancer cells, which is a crucial mediator of the interaction between stromal and cancer cells. CAF-CM significantly enhanced the HOTAIR expression to promote EMT, whereas treatment with small-molecule inhibitors of TGF-ß1 attenuated the activation of HOTAIR. Most importantly, SMAD2/3/4 directly bound the promoter site of HOTAIR, located between nucleotides -386 and -398, -440 and -452, suggesting that HOTAIR was a directly transcriptional target of SMAD2/3/4. Additionally, CAFs mediated EMT by targeting CDK5 signaling through H3K27 tri-methylation. Depletion of HOTAIR inhibited CAFs-induced tumor growth and lung metastasis in MDA-MB-231 orthotopic animal model. CONCLUSIONS: Our findings demonstrated that CAFs promoted the metastatic activity of breast cancer cells by activating the transcription of HOTAIR via TGF-ß1 secretion, supporting the pursuit of the TGF-ß1/HOTAIR axis as a target in breast cancer treatment.


Assuntos
Fibroblastos Associados a Câncer/metabolismo , Epigênese Genética , Neoplasias/genética , Neoplasias/metabolismo , Comunicação Parácrina , Animais , Fibroblastos Associados a Câncer/patologia , Linhagem Celular Tumoral , Movimento Celular/genética , Quinase 5 Dependente de Ciclina/genética , Quinase 5 Dependente de Ciclina/metabolismo , Transição Epitelial-Mesenquimal/genética , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Humanos , Camundongos , Metástase Neoplásica , Neoplasias/patologia , Prognóstico , RNA Longo não Codificante/genética , Transdução de Sinais , Proteínas Smad/genética , Proteínas Smad/metabolismo , Transcrição Gênica , Fator de Crescimento Transformador beta1/metabolismo
9.
J Cell Mol Med ; 21(7): 1361-1372, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28158928

RESUMO

Activation of osteoblasts in bone formation and osteoclasts in bone resorption is important during the bone fracture healing process. There has been a long interest in identifying and developing a natural therapy for bone fracture healing. In this study, we investigated the regulation of osteoclast differentiation by baicalin, which is a natural molecule extracted from Eucommiaulmoides (small tree native to China). It was determined that baicalin enhanced osteoclast maturation and bone resorption activity in a dose-dependent manner. Moreover, this involves the activation of MAPK, increased Mitf nuclear translocation and up-regulation of downstream osteoclast-related target genes expression. The baicalin-induced effect on osteoclast differentiation can be mimicked by specific inhibitors of p-ERK (U0126) and the Mitf-specific siRNA, respectively. Protein-ligand docking prediction identified that baicalin might bind to RANK, which is the upstream receptor of p-ERK/Mitf signalling in osteoclasts. This indicated that RANK might be the binding target of baicalin. In sum, our findings revealed baicalin increased osteoclast maturation and function via p-ERK/Mitf signalling. In addition, the results suggest that baicalin can potentially be used as a natural product for the treatment of bone fracture.


Assuntos
Flavonoides/administração & dosagem , Fraturas Ósseas/tratamento farmacológico , MAP Quinase Quinase 1/genética , Fator de Transcrição Associado à Microftalmia/genética , Receptor Ativador de Fator Nuclear kappa-B/genética , Animais , Reabsorção Óssea/genética , Reabsorção Óssea/fisiopatologia , Butadienos/administração & dosagem , Diferenciação Celular/efeitos dos fármacos , Fraturas Ósseas/genética , Fraturas Ósseas/fisiopatologia , Humanos , MAP Quinase Quinase 1/antagonistas & inibidores , Camundongos , Fator de Transcrição Associado à Microftalmia/antagonistas & inibidores , Nitrilas/administração & dosagem , Osteoclastos/efeitos dos fármacos , Osteoclastos/metabolismo , Osteogênese/genética , Ligação Proteica , Células RAW 264.7 , Transdução de Sinais/efeitos dos fármacos
10.
J Asian Nat Prod Res ; 19(2): 176-187, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28024413

RESUMO

Ferulic acid (FA) is an active component of the traditional Chinese herb Angelica sinensis. Numerous health benefits have been attributed to FA, but few studies have investigated the effects of FA on osteoblasts (Obs). Our work studied the effects of FA on proliferation, differentiation, and mineralization of rat calvarial Obs and examined the signaling pathways involved. Cell proliferation and differentiation were evaluated by Cell Counting Kit-8 (CCK-8) and alkaline phosphatase (ALP) assay kit, respectively. Cyclic guanosine monophosphate (cGMP)-dependent protein kinase II (PKGII) expression was silenced by small interfering RNA (siRNA). The mRNA expression was investigated by semi-quantitative PCR. FA (40-2560 µM) promoted Ob proliferation and differentiation; at 40-640 µM, FA stimulated calcified nodule formation and increased the expression of osteogenic genes encoding osteopontin and collagen-l. FA (40-2560 µM) increased cGMP levels in Obs and upregulated the expression of PKGII, EnaCα, and ENaCγ mRNAs. Downregulated ENaCα mRNA expression in Obs transfected with the siRNA for PKGII was reversed when FA was introduced into Obs. These results demonstrated that FA promoted proliferation, differentiation, and mineralization of Obs in vitro, and enhanced osteogenic genes expression partly through the cGMP-PKGII-ENaC signaling pathway.


Assuntos
Proliferação de Células/efeitos dos fármacos , Ácidos Cumáricos/farmacologia , Osteoblastos/efeitos dos fármacos , Fosfatase Alcalina/metabolismo , Animais , Diferenciação Celular , GMP Cíclico/metabolismo , Estrutura Molecular , Osteogênese/efeitos dos fármacos , Osteopontina , RNA Mensageiro/metabolismo , RNA Interferente Pequeno/genética , Ratos , Transdução de Sinais/efeitos dos fármacos
11.
Angew Chem Int Ed Engl ; 56(13): 3594-3598, 2017 03 20.
Artigo em Inglês | MEDLINE | ID: mdl-28217911

RESUMO

Tuning the surface strain of heterogeneous catalysts represents a powerful strategy to engineer their catalytic properties by altering the electronic structures. However, a clear and systematic understanding of strain effect in electrochemical reduction of carbon dioxide is still lacking, which restricts the use of surface strain as a tool to optimize the performance of electrocatalysts. Herein, we demonstrate the strain effect in electrochemical reduction of CO2 by using Pd octahedra and icosahedra with similar sizes as a well-defined platform. The Pd icosahedra/C catalyst shows a maximum Faradaic efficiency for CO production of 91.1 % at -0.8 V versus reversible hydrogen electrode (vs. RHE), 1.7-fold higher than the maximum Faradaic efficiency of Pd octahedra/C catalyst at -0.7 V (vs. RHE). The combination of molecular dynamic simulations and density functional theory calculations reveals that the tensile strain on the surface of icosahedra boosts the catalytic activity by shifting up the d-band center and thus strengthening the adsorption of key intermediate COOH*. This strain effect was further verified directly by the surface valence-band photoemission spectra and electrochemical analysis.

12.
Nanomedicine (Lond) ; 19(8): 657-669, 2024 04.
Artigo em Inglês | MEDLINE | ID: mdl-38305028

RESUMO

Background: Osteoarthritis causes tremendous damage to the joints, reducing the quality of life and imposing significant financial burden. An implantable drug-delivery system can improve the symptomatic manifestations with low doses and frequencies. However, the free drug has short retention in the joint cavity. Materials & methods: This study used electrostatic spinning technology to create an implantable drug-delivery system loaded with celecoxib (celecoxib nanofibers [Cel-NFs]) to improve retention and bioavailability. Results: Cel-NFs exhibited good formability, hydrophilicity and tensile properties. Cel-NFs were able to continuously release drugs for 2 weeks and increase the uptake capacity of Raw 264.7 cells, ultimately ameliorating symptoms in osteoarthritis rats. Conclusion: These results suggest that Cel-NFs can effectively ameliorate cartilage damage, reduce joint pain and alleviate osteoarthritis progression.


Assuntos
Nanofibras , Osteoartrite , Ratos , Animais , Celecoxib/uso terapêutico , Qualidade de Vida , Osteoartrite/tratamento farmacológico , Eletricidade Estática
13.
ACS Appl Mater Interfaces ; 15(3): 4643-4651, 2023 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-36630692

RESUMO

High-entropy transition-metal oxides are potentially interesting cathode materials for lithium-ion batteries, among which high-entropy layered oxides are considered highly promising because there exist two-dimensional ion transport channels that may, in principle, enable fast ion transport. However, high-entropy layered oxides reported to date exhibit fast capacity fading in initial cycles and thus are hardly of any practical value. Here, we investigate the structural and property changes of a five-element layered oxide, LiNi0.2Co0.2Mn0.2Fe0.2Al0.2O2, using electrochemical and physical characterization techniques. It is revealed that the M3O4 phase formed at the surface of LiNi0.2Co0.2Mn0.2Fe0.2Al0.2O2 due to the migration of metal ions from octahedral sites of the transition-metal layer to tetrahedral 8a and octahedral sites of the lithium layer hinders the intercalation of lithium ion, which leads to the low initial Coulombic efficiency and fast decay of reversible capacity. This mechanism could be generally applicable to other high-entropy layered oxides with different elemental compositions.

14.
Pharmaceutics ; 15(3)2023 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-36986590

RESUMO

This study presents a method for a one-step co-encapsulation of PLGA nanoparticles in hydrophilic nanofibers. The aim is to effectively deliver the drug to the lesion site and achieve a longer release time. The celecoxib nanofiber membrane (Cel-NPs-NFs) was prepared by emulsion solvent evaporation and electrospinning with celecoxib as a model drug. By this method, nanodroplets of celecoxib PLGA are entrapped within polymer nanofibers during an electrospinning process. Moreover, Cel-NPs-NFs exhibited good mechanical strength and hydrophilicity, with a cumulative release of 67.74% for seven days, and the cell uptake at 0.5 h was 2.7 times higher than that of pure nanoparticles. Furthermore, pathological sections of the joint exhibited an apparent therapeutic effect on rat OA, and the drug was delivered effectively. According to the results, this solid matrix containing nanodroplets or nanoparticles could use hydrophilic materials as carriers to prolong drug release time.

15.
Innovation (Camb) ; 4(2): 100391, 2023 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-36873268

RESUMO

Echinacea purpurea modulates tumor progression, but the underlying mechanism is poorly defined. We isolated and purified a novel homogeneous polysaccharide from E. purpurea (EPPA), which was shown to be an arabinogalactan with a mean molecular mass (Mr) of 3.8 × 104 Da and with α- (1 → 5) -L-Arabinan as the backbone and α-L-Araf-(1→, →6)-ß-D-Galp-(1→, and →4)-α-D-GalpA-(1→ as the side chains. Interestingly, oral administration of EPPA suppresses tumor progression in vivo and shapes the immune cell profile (e.g., facilitating M1 macrophages) in tumor microenvironment by single-cell RNA sequencing (scRNA-seq) analysis. More importantly, EPPA activates the inflammasome through a phagocytosis-dependent mechanism and rewires transcriptomic and metabolic profile, thereby potentiating M1 macrophage polarization. Collectively, we propose that EPPA supplementation could function as an adjuvant therapeutic strategy for tumor suppression.

16.
Cell Biol Toxicol ; 28(5): 279-89, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22752439

RESUMO

PURPOSE: Glucocorticoids (GCs) can facilitate bone formation, but prolonged GCs exposure in vivo can lead to osteoporosis. The mechanisms underlying these reciprocal effects have not been elucidated. METHODS: The epithelial sodium channel (ENaC) is a possible regulator of osteoblast proliferation and differentiation, so we examined whether ENaC was involved in mediating the effects of dexamethasone (Dex) on osteoblast. RESULT: Expression of the functional α-ENaC subunit was upregulated by 10(-8)M and 10(-6)M Dex, but decreased by 10(-4)M Dex. Furthermore, Dex had similar dose-dependent effects on the expression of three osteogenic genes, Cbfa1, OPN, and OC, with low concentrations enhancing expression and higher concentrations suppressing expression. The effects of Dex on osteoblast proliferation, differentiation, and mineralization were examined in the presence and absence of the ENaC specific antagonist amiloride. Dex at 10(-8)M and 10(-6)M markedly increased osteoblast proliferation, alkaline phosphatase activity (an index of differentiation), and calcium nodule formation, while 10(-4)M had no effect or suppressed all these responses. Amiloride blocked the Dex-induced, osteoblast differentiation and mineralization but had no effect on osteoblast differentiation and mineralization when applied alone. But such changes did not show in osteoblast proliferation. However, the Dex-induced α-ENaC expression was not blocked by RU486, a GC receptor antagonist. CONCLUSION: These results suggest that changes in ENaC activity may involved in Dex-induced differentiation and mineralization of osteoblast. But the Dex-induced effect on ENaC did not mediated by the GC genomic mechanism in osteoblast at this study.


Assuntos
Calcificação Fisiológica/efeitos dos fármacos , Dexametasona/farmacologia , Canais Epiteliais de Sódio/metabolismo , Glucocorticoides/farmacologia , Osteoblastos/efeitos dos fármacos , Subunidades Proteicas/metabolismo , Fosfatase Alcalina/metabolismo , Amilorida/farmacologia , Animais , Animais Recém-Nascidos , Biomarcadores/metabolismo , Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Subunidade alfa 1 de Fator de Ligação ao Core/genética , Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo , Relação Dose-Resposta a Droga , Bloqueadores do Canal de Sódio Epitelial/farmacologia , Canais Epiteliais de Sódio/genética , Expressão Gênica/efeitos dos fármacos , Antagonistas de Hormônios/farmacologia , Mifepristona/farmacologia , Osteoblastos/citologia , Osteoblastos/metabolismo , Cultura Primária de Células , Subunidades Proteicas/genética , Ratos , Regulação para Cima/efeitos dos fármacos
17.
Front Surg ; 9: 992490, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36386543

RESUMO

Background: Endometriosis is now considered to be a systemic disease rather than a disease that primarily affects the pelvis. Dienogest (DNG) has unique advantages in the treatment of endometriosis, but it also has side effects. Alternatively, Traditional Chinese Medicine (TCM) has been used for over 2000 years in the treatment and prevention of disease and growing numbers of Chinese scholars are experimenting with the combined use of Dienogest and TCM for endometriosis treatment. Objectives: This review evaluated the efficacy and safety of TCM in combination with Dienogest in the treatment of endometriosis through meta-analysis. Methods: MEDLINE, Embase, the Cochrane Library, PubMed, Web of Science, China National Knowledge Infrastructure, Journal Integration Platform, and Wanfang were used in literature searches, with a deadline of May 31, 2022. Literature quality was assessed using the Cochrane Collaboration "risk of bias" (ROB2) tool, and the "meta" package of R software v.4.1 was used for meta-analysis. Dichotomous variables and continuous variables were assessed using the relative risk (RR) and 95% confidence intervals (95% CI); standard mean differences (MD) and 95% CI, respectively. Results: Twelve human randomized controlled trials (RCTs) and one retrospective study, all 13 written in the Chinese language, were included in the meta-analysis (720 experiments and 719 controls). The result indicated that TCM plus Dienogest was superior to Dienogest/TCM alone in increasing the cure rates (RR = 1.3780; 95% CI, 1.1058, 1.7172; P = 0.0043), remarkable effect rate (RR = 1.3389; 95% CI, 1.1829, 1.5154; P < 0.0001), invalid rate (RR = 0.2299; 95% CI, 0.1591, 0.3322; P < 0.0001), and rate of adverse effects (RR = 0.6177; 95% CI, 0.4288, 0.8899; P = 0.0097). The same conclusion was drawn from the subgroup analysis. Conclusion: Results suggest that TCM combined with Dienogest is superior to Dienogest or TCM alone and can be used as a complementary treatment for endometriosis. TCMs have potential to improve clinical efficacy and reduce the side effects of Dienogest. This study was financially supported by Annual Science and Technology Steering Plan Project of Zhuzhou. PROSPERO has registered our meta-analysis as CRD42022339518 (https://www.crd.york.ac.uk/prospero/record_email.php).

18.
Front Public Health ; 10: 836113, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35570903

RESUMO

Objectives: This study aims to evaluate the direct effects of work stress, health status and presenteeism on task performance, and further explore the mediating effects of health status and presenteeism, hoping to provide theoretical basis for improving the performance of medical staff. Methods: A cross-sectional study was conducted among medical staff in Jilin Province, Northeast China. The Challenge and Hindrance-Related Self-Reported Stress scale, Short Form-8 Health Survey scale, Stanford Presenteeism Scale and Task Performance Scale were adopted to assess the work stress, health status, presenteeism and task performance of medical staff. Results: A total of 4,347 questionnaires were distributed among medical staff, and 4261 were valid, for an effective rate of 98.02%. The mean scores for work stress, health status, presenteeism and task performance were 2.05 ± 0.84, 4.18 ± 0.68, 2.15 ± 0.79 and 4.49 ± 0.64, respectively. The ANOVA results showed that there were significant differences in the task performance scores between different genders, ages, marital statuses, professional titles, departments and work years (P < 0.05). Work stress (ß = -0.136, P < 0.001) and presenteeism (ß = -0.171, P < 0.001) were negative predictors of task performance. Health status (ß = 0.10; P < 0.001) was positive predictor of task performance. Health status (ß = -0.070; P < -0.001) and presenteeism (ß = -0.064; P < 0.001) mediated the relationship between work stress and task performance (P < 0.001). Presenteeism mediated the relationship between health status and task performance (ß = 0.07; P < 0.001). Conclusion: Work stress and presenteeism had significant negative impact on the task performance of medical staff; health status had a significant positive effect on task performance. Meanwhile, health status and presenteeism played a mediating role in the relationship between work stress and task performance, and presenteeism played a mediating role in the relationship between health status and task performance. Reasonable assignment of tasks can reduce the work stress, but to improve the performance of medical staff, we should pay more attention on improving health, such as making health-related safeguard measures, raising awareness, building a platform, etc.


Assuntos
COVID-19 , Estresse Ocupacional , COVID-19/epidemiologia , China/epidemiologia , Estudos Transversais , Feminino , Nível de Saúde , Humanos , Masculino , Corpo Clínico , Estresse Ocupacional/epidemiologia , Pandemias , Presenteísmo , Análise e Desempenho de Tarefas
19.
Artigo em Inglês | MEDLINE | ID: mdl-35270475

RESUMO

In China, the primary health care institutions (PHCIs) have difficulty winning the trust of residents because of the shortage of medical personnel and the low level of skills. The government has advocated encouraging qualified doctors to work in PHCIs, but no obvious results are achieved. Based on the theory of planned behavior (TPB), this paper explores the factors affecting medical personnel seeking employment in PHCIs and then putting forward measures to improve the human resources construction of PHCIs. A three-stage survey was conducted to obtain the factors and a structural equation modeling (SEM) was applied to examine the relationship of the factors. We found that the factors affecting medical personnel to work in PHCIs include the specific conditions and work contents of PHCIs, as well as the family life and regional factors. Besides, there is a significant correlation and indirectness between these factors. Therefore, targeted measures can be proposed to improve the intention of medical personnel seeking employment in PHCIs. This study provides theoretical support for encouraging medical personnel to work in PHCIs and improving the primary health care system.


Assuntos
Médicos , Atenção à Saúde , Humanos , Intenção , Atenção Primária à Saúde , Inquéritos e Questionários , Recursos Humanos
20.
Front Pharmacol ; 13: 921387, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35795549

RESUMO

Objective: This study aimed to investigate the cost-effectiveness of low-dose rivaroxaban plus aspirin versus aspirin alone for patients with stable cardiovascular diseases in the China. Methods: We used TreeAge 2019 to construct a Markov model to assess the direct healthcare costs and quality-adjusted life years for three therapies, namely low-does rivaroxaban plus aspirin, rivaroxaban alone, and aspirin alone. Transitional probabilities were derived from the COMPASS trial, and the costs and utilities were obtained from the Chinese Health Care Statistical Yearbook and published studies. Use the Incremental cost-effectiveness ratio to describe the results. The willingness-to-pay threshold is set at US$11,000 (China's 2020 Gross National Product per capita). Result: In patients with stable cardiovascular disease, the increased cost per quality-adjusted life year gained in the low-dose rivaroxaban combined with aspirin group compared to the aspirin alone group was US$7937.30. The increased cost per quality-adjusted life year gained in the rivaroxaban alone group versus the aspirin alone group was US$15,045.78. Conclusion: A low-does rivaroxaban plus aspirin therapy may be cost-effective in the secondary prevention of stable cardiovascular disease in patients.

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