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1.
Hum Reprod ; 38(12): 2382-2390, 2023 Dec 04.
Artículo en Inglés | MEDLINE | ID: mdl-37801294

RESUMEN

STUDY QUESTION: Can blastocyst aneuploidy be predicted for patients with previous aneuploid pregnancy loss (PAPL) and receiving preimplantation genetic testing for aneuploidy (PGT-A)? SUMMARY ANSWER: Multivariable logistic regression models were established to predict high risk of blastocyst aneuploidy using four identified factors, presenting good predictive performance. WHAT IS KNOWN ALREADY: Aneuploidy is the most common embryonic chromosomal abnormality leading to pregnancy loss. Several studies have demonstrated a higher embryo aneuploidy rate in patients with PAPL, which has suggested that PGT-A should have benefits in PAPL patients intending to improve their pregnancy outcomes. However, recent studies have failed to demonstrate the efficacy of PGT-A for PAPL patients. One possible way to improve the efficacy is to predict the risk of blastocyst aneuploidy risk in order to identify the specific PAPL population who may benefit from PGT-A. STUDY DESIGN, SIZE, DURATION: We conducted a multicenter retrospective cohort study based on data analysis of 1119 patients receiving PGT-A in three reproductive medical centers of university affiliated teaching hospitals during January 2014 to June 2020. A cohort of 550 patients who had one to three PAPL(s) were included in the PAPL group. In addition, 569 patients with monogenic diseases without pregnancy loss were taken as the non-PAPL group. PARTICIPANTS/MATERIALS, SETTING, METHODS: PGT-A was conducted using single nucleotide polymorphism microarrays and next-generation sequencing. Aneuploidy rates in Day 5 blastocysts of each patient were calculated and high-risk aneuploidy was defined as a rate of ≥50%. Candidate risk factors for high-risk aneuploidy were selected using the Akaike information criterion and were subsequently included in multivariable logistic regression models. Overall predictive accuracy was assessed using the confusion matrix, discrimination by area under the receiver operating characteristic curve (AUC), and calibration by plotting the predicted probabilities versus the observed probabilities. Statistical significance was set at P < 0.05. MAIN RESULTS AND THE ROLE OF CHANCE: Blastocyst aneuploidy rates were 30 ± 25% and 21 ± 19% for PAPL and non-PAPL groups, respectively. Maternal age (odds ratio (OR) = 1.31, 95% CI 1.24-1.39, P < 0.001), number of PAPLs (OR = 1.40, 95% CI 1.05-1.86, P = 0.02), estradiol level on the ovulation trigger day (OR = 0.47, 95% CI 0.30-0.73, P < 0.001), and blastocyst formation rate (OR = 0.13, 95% CI 0.03-0.50, P = 0.003) were associated with high-risk of blastocyst aneuploidy. The predictive model based on the above four variables yielded AUCs of 0.80 using the training dataset and 0.83 using the test dataset, with average and maximal discrepancies of 2.89% and 12.76% for the training dataset, and 0.98% and 5.49% for the test dataset, respectively. LIMITATIONS, REASONS FOR CAUTION: Our conclusions might not be compatible with those having fewer than four biopsied blastocysts and diminished ovarian reserves, since all of the included patients had four or more biopsied blastocysts and had exhibited good ovarian reserves. WIDER IMPLICATIONS OF THE FINDINGS: The developed predictive model is critical for counseling PAPL patients before PGT-A by considering maternal age, number of PAPLs, estradiol levels on the ovulation trigger day, and the blastocyst formation rate. This prediction model achieves good risk stratification and so may be useful for identifying PAPL patients who may have higher risk of blastocyst aneuploidy and can therefore acquire better pregnancy outcomes by PGT-A. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the National Natural Science Foundation of China under Grant (81871159). No competing interest existed in the study. TRIAL REGISTRATION NUMBER: N/A.


Asunto(s)
Aborto Espontáneo , Diagnóstico Preimplantación , Embarazo , Humanos , Femenino , Diagnóstico Preimplantación/métodos , Estudios Retrospectivos , Blastocisto/patología , Pruebas Genéticas/métodos , Resultado del Embarazo , Aborto Espontáneo/genética , Aborto Espontáneo/patología , Aneuploidia , Estradiol
2.
Int J Pharm ; 646: 123440, 2023 Nov 05.
Artículo en Inglés | MEDLINE | ID: mdl-37742824

RESUMEN

Amorphous solid dispersion (ASD) is one of the formulation strategies for drugs displaying low solubility and low oral bioavailability. In this study, high drug-loaded ASDs of drugs with different crystallization tendencies were prepared by spray drying. The aim was to investigate the influence of hydrogen bonding between the drug and the model polymer PVPVA on the physical stability of ASDs containing drugs with different crystallization tendencies. From the 60-day stability study results, the intermolecular hydrogen bonding has a considerable stabilizing effect on the ASDs of the drug with a moderate crystallization tendency. Nimesulide (hydrogen bond donor) can maintain the amorphous form for a longer time than Fenofibrate (no-hydrogen bond donor) during storage. In the ASDs with fast crystallization tendency drugs (naproxen and caffeine), intermolecular hydrogen bonds are not very effective in preventing drug crystallization, and the effect on the stability of ASD is relatively weak. However, for drugs with a slow tendency to crystallize (indomethacin and miconazole), the ASDs remained in an amorphous state during the monitored storage period, making it impossible to compare the effect of intermolecular hydrogen bonds on the stability of this type of ASDs. It also reveals that intermolecular hydrogen bonds can increase the drug loading capacity of ASDs. The relationship between drug loading and ASD stability was further analyzed by the state diagram. This study clearly pointed out that the physical stability of ASDs of drugs with different crystallization tendencies is affected to a different extent by intermolecular hydrogen bonds.

3.
Biomater Sci ; 11(21): 7203-7215, 2023 Oct 24.
Artículo en Inglés | MEDLINE | ID: mdl-37750690

RESUMEN

Pelvic organ prolapse (POP) is one of the common diseases in middle-aged and elderly women, caused by weakened pelvic floor muscle ligament tissue support. Pelvic floor reconstruction with mesh implantation has been proven to be an effective treatment for POP. However, traditional non-degradable and inflexible pelvic floor implantation meshes have been associated with pain, vaginal infections, and the need for additional surgeries. In this study, novel meshes with pre-designed structures were fabricated with solution-based electrohydrodynamic printing (EHDP) technology, using a series of polycaprolactone/silk fibroin composites as bioinks. The PCL/SF mesh mechanical performances were particularly enhanced with the addition of silk II, leading it to obtain higher adaptability with soft tissue repair. The mesh containing SF showed more robust degradation performance in the in vitro degradation assay. Furthermore, biocompatibility tests conducted on mouse embryonic fibroblasts (NIH/3T3) revealed enhanced cell affinity. Finally, the biocompatibility and tissue repair properties of PCL/SF mesh were verified through the implantation of meshes in the muscle defect site of mice. The results demonstrated that the 3D printed PCL/SF mesh prepared by EHDP exhibits superior mechanical properties, biocompatibility, biodegradability, as well as ligament and muscle fiber repair ability. The novel implantable meshes are promising for curing POP.

4.
Analyst ; 148(19): 4659-4667, 2023 Sep 25.
Artículo en Inglés | MEDLINE | ID: mdl-37615041

RESUMEN

We report a fully integrated digital microfluidic absorbance detection system with an enhanced sensitivity for online bacterial monitoring. Through a 100 µm gap in the chip, our optical detection system has a detection sensitivity for a BCA protein concentration of 0.1 mg mL-1. The absorbance detection limit of our system is 1.4 × 10-3 OD units, which is one order of magnitude better than that of the existing studies. The system's linear region is 0.1-7 mg mL-1, and the dynamic range is 0-25 mg mL-1. We measured the growth curves of wild-type and E. coli transformed with resistance plasmids and mixed at different ratios on chip. We sorted out the bacterial species including highly viable single cells based on the difference in absorbance data of growth curves. We explored the changes in the growth curves of E. coli under different concentrations of resistant media. In addition, we successfully screened for the optimal growth environment of the bacteria, in which the growth rate of PET30a-DH5α (in a medium with 33 µg mL-1 kanamycin resistance) was significantly higher than that of a 1 mg mL-1 resistance medium. In conclusion, the enhanced digital microfluidic absorbance detection system exhibits exceptional sensitivity, enabling precise bacterial monitoring and growth curve analysis, while also laying the foundation for DMF-based automated bioresearch platforms, thus advancing research in the life sciences.


Asunto(s)
Microfluídica , Dispositivos Ópticos , Escherichia coli , Dispositivos Laboratorio en un Chip , Movimiento Celular
5.
Research (Wash D C) ; 6: 0101, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37040295

RESUMEN

The durability of the resin-dentin bonding interface is a key issue in clinical esthetic dentistry. Inspired by the extraordinary bioadhesive properties of marine mussels in a wet environment, we designed and synthetized N-2-(3,4-dihydroxylphenyl) acrylamide (DAA) according to the functional domain of mussel adhesive proteins. DAA's properties of collagen cross-linking, collagenase inhibition, inducing collagen mineralization in vitro, and as a novel prime monomer for clinical dentin adhesion use, its optimal parameters, and effect on the adhesive longevity and the bonding interface's integrity and mineralization, were evaluated in vitro and in vivo. The results showed that oxide DAA can inhibit the activity of collagenase and cross collagen fibers to improve the anti-enzymatic hydrolysis of collagen fibers and induce intrafibrillar and interfibrillar collagen mineralization. As a primer used in the etch-rinse tooth adhesive system, oxide DAA can improve the durability and integrity of the bonding interface by anti-degradation and mineralization of the exposed collagen matrix. Oxidized DAA (OX-DAA) is a promising primer for improving dentin durability; using 5% OX-DAA ethanol solution and treating the etched dentin surface for 30 s is the optimal choice when used as a primer in the etch-rinse tooth adhesive system.

6.
Hua Xi Kou Qiang Yi Xue Za Zhi ; 40(6): 662-667, 2022 Dec 01.
Artículo en Inglés, Chino | MEDLINE | ID: mdl-36416318

RESUMEN

OBJECTIVES: This work aimed to synthesize a novel injectable alginate impression material and evaluate its accuracy. METHODS: Certain proportions of sodium alginate, trisodium phosphate dodecahydrate, potassium fluorotitanate, diatomaceous earth, and other ingredients were dissolved in water and mixed evenly with a planetary centrifugal mixer to obtain a certain viscosity base paste. Certain proportions of calcium sulfate hemihydrate, magnesium oxide, glycerin, and polyethylene glycol (PEG) 400 were mixed evenly with a planetary centrifugal mixer to obtain the reactor paste with the same viscosity as the base paste. The base and reactor pastes were poured into a two-cylinder cartridge at a 2∶1 volume ratio. A gun device was used to accomplish mixing by compressing materials into a mixing tip. The samples were divided into three groups: injectable alginate impression materials (IA group) as the experimental group, and Jeltrate alginate impression materials (JA group) and Silagum-putty/light addition silicone rubber impression materials (SI group) as the two control groups. RESULTS: Scanning electron microscopy (SEM) showed that the injectable alginate impression materials had a denser structure and fewer bubbles than the commercial alginate impression material. The accuracy of the three kinds of impression materials was evaluated by 3D image superposition. The deviations between the three test group models and the standard model (trueness) were 49.58 µm±1.453 µm (IA group), 54.75 µm±7.264 µm (JA group), and 30.92 µm±1.013 µm (SI group). The deviations of the models within each test group (precision) were 85.79 µm±8.191 µm (IA group), 97.65 µm±11.060 µm (JA group), and 56.51 µm±4.995 µm (SI group). Significant differences in trueness and precision were found among the three kinds of impression materials (P<0.05). CONCLUSIONS: The accuracy of the new injectable alginate impression material was better than that of the traditional powder-type alginate impression material but worse than that of the addition silicone rubber impression materials. The novel injec-table alginate impression material demonstrated good operation performance and impression accuracy, showing broad application prospect.


Asunto(s)
Alginatos , Elastómeros de Silicona , Alginatos/química , Elastómeros de Silicona/química , Materiales de Impresión Dental/química , Polvos
7.
Future Oncol ; 18(2): 149-161, 2022 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-34643088

RESUMEN

Background: Chemoresistance usually occurs in ovarian cancer. We aimed to explore the mechanisms of chemoresistance. Methods: Western blotting assay was used to detect the expression of GALNT14. Further cell function experiments were performed to investigate the effect of GALNT14 in ovarian cancer. Results: GALNT14 is significantly upregulated in ovarian cancer. Downregulation of GALNT14 significantly inhibits both apoptosis and ferroptosis of ovarian cancer cells. A further mechanism assay illustrated that downregulation of GALNT14 suppresses the activity of the mTOR pathway through modifying O-glycosylation of EGFR. Finally, an additive effect promoting cell death occurs with a combination of an mTOR inhibitor and cisplatin. Conclusion: Our study might provide a promising method to overcome cisplatin resistance for patients with ovarian cancer.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Cisplatino/farmacología , Resistencia a Antineoplásicos/genética , N-Acetilgalactosaminiltransferasas/metabolismo , Neoplasias Ováricas/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Apoptosis/efectos de los fármacos , Apoptosis/genética , Línea Celular Tumoral , Cisplatino/uso terapéutico , Resistencia a Antineoplásicos/efectos de los fármacos , Receptores ErbB/metabolismo , Femenino , Ferroptosis/efectos de los fármacos , Ferroptosis/genética , Regulación Neoplásica de la Expresión Génica , Glicosilación/efectos de los fármacos , Humanos , Persona de Mediana Edad , Neoplasias Ováricas/genética , Neoplasias Ováricas/patología , Ovario/patología , Transducción de Señal/efectos de los fármacos , Transducción de Señal/genética , Sirolimus/análogos & derivados , Sirolimus/farmacología , Sirolimus/uso terapéutico , Serina-Treonina Quinasas TOR/antagonistas & inhibidores , Serina-Treonina Quinasas TOR/metabolismo , Regulación hacia Arriba
8.
Artículo en Inglés | MEDLINE | ID: mdl-34769748

RESUMEN

Pesticide adjuvants (PAs) are important components of pesticide. Nonetheless, limited information is available regarding their toxic effects on biota in terrestrial ecosystem. In the present study, the mortality, growth inhibition ratio, and avoidance behavior of Eisenia fetida were examined to investigate the ecotoxicological effects of toluene, xylene, and trichloroethylene and further their mixture. The 24 h median lethal concentration (24 h-LC50) of the three PAs were 300.23, 1190.45, and 5332.36 mg/kg, and the 48 h-LC50 values were 221.62, 962.89, and 4522.41 mg/kg, respectively. The mixture exhibited significant synergistic effect on the E. fetida. There was significant growth inhibition on E. fetida by the tested PAs. The avoidance threshold values of E. fetida for the tested PAs were 1100 mg/kg, 250 mg/kg, 5000 mg/kg, and 25% of the mixture, respectively. The results evaluated the toxic effects of the three PAs and their mixture on E. fetida, provided a basis for ecotoxicological risk assessment of PAs in the soil ecosystem.


Asunto(s)
Oligoquetos , Plaguicidas , Contaminantes del Suelo , Animales , Ecosistema , Plaguicidas/toxicidad , Medición de Riesgo , Contaminantes del Suelo/análisis
9.
PLoS One ; 16(9): e0255504, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34473729

RESUMEN

Benzophenone (BPs) and 4-Methylbenzylidene Camphor are used as ultraviolet (UV) filters to protect the skin and hair in personal care products. The discharging of the three chemicals may endanger the receiving water ecosystem. In the present study, the mutagenicity of BP-6, BP-8, and 4-Methylbenzylidene Camphor was tested using the Salmonella typhimurium reverse mutation test (Ames test) in the system with and without rat liver microsomal preparations (S9). Four S.typhimurium strains, TA97, TA98, TA100, and TA102 were employed in the Ames tests. The mutagenicity was detected from all three chemicals. The addition of S9 increased the mutation ratios of three chemicals to four strains, except BP-6 to TA100 strain and 4-MBC to TA97 and TA98 strain. In the mixed experiment, all positive effects were detected in the absence of S9. However, the results all became negative in the presence of S9. For the mixture of BP-6 and 4-MBC, positive results were detected on four tester strains except for the TA100 strain. For the mixture of BP-6, BP-8, and 4-MBC, positive results were detected on four strains. The mixture test results showed antagonism in mutagenicity for the mixture of BP-6 and 4-MBC to TA98 and TA100 strains and the mixture of BP-6, BP-8, and 4-MBC to TA100 and TA102 strains.


Asunto(s)
Benzofenonas/toxicidad , Alcanfor/análogos & derivados , Mutagénesis/efectos de los fármacos , Pruebas de Mutagenicidad/métodos , Salmonella typhimurium/efectos de los fármacos , Protectores Solares/toxicidad , Rayos Ultravioleta/efectos adversos , Animales , Bioensayo , Alcanfor/toxicidad , Monitoreo del Ambiente/métodos , Humanos , Microsomas Hepáticos/efectos de los fármacos , Ratas , Salmonella typhimurium/genética
10.
Artículo en Inglés | MEDLINE | ID: mdl-34360388

RESUMEN

Pesticide adjuvants (PAs) denote the general term for auxiliaries in pesticide preparations except for the active components. Toluene, chloroform, and trichloroethylene are the three most commonly used PAs as organic solvents. The residues of the three chemicals in the process of production and application of pesticides may endanger the ecosystem. In the present study, the mutagenicity of toluene, chloroform, and trichloroethylene as well the mixture of the three chemicals was tested by the Salmonella typhimurium reverse mutation test (Ames test) with TA97, TA98, TA100, and TA102 strains in the system with and without rat liver microsomal preparations (S9). The four tester strains have been used for more than 40 years to detect mutagenic compounds in chemicals, cosmetics, and environmental samples. The mutagenicity was detected on tester strains in the separated experiment from the three chemicals. The addition of S9 decreased the mutation ratios of toluene to four strains, except for the TA100 strain, but increased the mutation ratios of chloroform to four strains except for the TA98 strain. Trichloroethylene caused positive mutagenicity to become negative on the TA102 strain. In the mixed experiment, positive effects were detected only on the TA102 strain in the absence of S9. The addition of S9 increased the mutagenicity except for the TA102 strain. The mixture of toluene, chloroform, and trichloroethylene showed antagonism in mutagenicity to tester strains, except for the TA102 strain without S9. However, the mixture showed a synergistic effect to tester strains after adding S9 except for the TA98 strain.


Asunto(s)
Plaguicidas , Tricloroetileno , Animales , Cloroformo/toxicidad , Ecosistema , Pruebas de Mutagenicidad , Mutágenos , Ratas , Tolueno/toxicidad , Tricloroetileno/toxicidad
11.
Huan Jing Ke Xue ; 42(7): 3518-3526, 2021 Jul 08.
Artículo en Chino | MEDLINE | ID: mdl-34212678

RESUMEN

Research on the characteristics of environmental background values of soil can provide a scientific basis for setting regional standards for soils. To determine the characteristics of environmental background values and main influencing factors of heavy metals (Cr, Cu, Zn, Ni, Pb, Co, V, Cd, and Hg) in soils in Shenzhen, 500 topsoil samples (0-20 cm) were collected by decision unit multi increment sampling (DUMS) from 500 soil background sites in the whole city, including 405 latosolic red soil, 77 red soil, and 18 yellow soil samples. The results show that the concentrations of heavy metals in red soil are relatively low in general, and those of Cr, Ni, Co, and V in latosolic red soil and Cu, Zn, Hg, Pb, and Cd in yellow soil are higher. Compared with the environmental background values of soil in the Seventh Five-year Plan of China in 1980s, the concentrations of Cr, Cu, Zn, Ni, Co, and V in latosolic red soil, red soil, and yellow soil are lower, the concentrations of Cd and Hg are similar, and the concentration of Pb is higher. The spatial distribution patterns of the nine heavy metals are significantly different. Pb, Zn, and Co present an obvious zonal distribution pattern, while Cr, Cu, Ni, V, Cd, and Hg present a point-like distribution pattern. Moreover, the correlation analysis between heavy metal content and physicochemical properties of different soils showed that the correlation between heavy metal content and physicochemical properties of latosolic red soil was the most significant. Stepwise regression analysis was used to elucidate the relationship between heavy metal content in latosolic red soil, and physicochemical properties were quantified. The physicochemical properties affecting heavy metal content in latosolic red soil were found to be mechanical composition, pH, organic matter, and cation exchange capacity.


Asunto(s)
Metales Pesados , Contaminantes del Suelo , China , Ciudades , Monitoreo del Ambiente , Metales Pesados/análisis , Medición de Riesgo , Suelo , Contaminantes del Suelo/análisis
12.
PLoS One ; 16(4): e0249915, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33831101

RESUMEN

Ultraviolet (UV) filters are used in cosmetics, personal care products and packaging materials to provide sun protection for human skin and other substances. Little is known about these substances, but they continue to be released into the environment. The acute toxicity of 4,4'-dihydroxybenzophenone, 2,4,4'-trihydroxybenzophenone and 4-MBC to Chlorella vulgaris and Daphnia magna were analyzed in this study. The 96 h-EC50 values of 4,4'-dihydroxybenzophenone, 2,4,4'-trihydroxybenzophenone and 4-MBC on C. vulgaris were 183.60, 3.50 and 0.16874 mg/L, respectively. The 48 h-LC50 of 4,4'-dihydroxybenzophenone, 2,4,4'-trihydroxybenzophenone and 4-MBC on D. magna were 12.50, 3.74 and 0.54445 mg/L, respectively. The toxicity of a mixture of 4,4'-dihydroxybenzophenone and 4-MBC showed addictive effect on C. vulgaris, while the toxicity of mixtures of 4,4'-dihydroxybenzophenone and 2,4,4'-trihydroxybenzophenone, 2,4,4'-trihydroxybenzophenone and 4-MBC as well as 4,4'-dihydroxybenzophenone, 2,4,4'-trihydroxybenzophenone and 4-MBC all showed antagonistic effect on C. vulgaris. The induced no-effect concentrations of 4,4'-dihydroxybenzophenone, 2,4,4'-trihydroxybenzophenone and 4-MBC by the assessment factor (AF) method were 0.0125, 0.00350 and 0.000169 mg/L, respectively.


Asunto(s)
Benzofenonas/toxicidad , Alcanfor/análogos & derivados , Chlorella vulgaris/crecimiento & desarrollo , Daphnia/crecimiento & desarrollo , Animales , Benzofenonas/química , Alcanfor/química , Alcanfor/toxicidad , Chlorella vulgaris/efectos de los fármacos , Daphnia/efectos de los fármacos , Sinergismo Farmacológico , Estructura Molecular , Protectores Solares/química , Protectores Solares/toxicidad , Pruebas de Toxicidad Aguda
13.
ACS Appl Mater Interfaces ; 13(3): 3722-3737, 2021 Jan 27.
Artículo en Inglés | MEDLINE | ID: mdl-33439616

RESUMEN

Pulmonary delivery of small interfering RNA (siRNA)-based drugs is promising in treating severe lung disorders characterized by the upregulated expression of disease-causing genes. Previous studies have shown that the sustained siRNA release in vitro can be achieved from polymeric matrix nanoparticles based on poly(lactide-co-glycolide) (PLGA) loaded with lipoplexes (LPXs) composed of cationic lipid and anionic siRNA (lipid-polymer hybrid nanoparticles, LPNs). Yet, the in vivo efficacy, potential for prolonging the pharmacological effect, disposition, and safety of LPNs after pulmonary administration have not been investigated. In this study, siRNA against enhanced green fluorescent protein (EGFP-siRNA) was either assembled with 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) to form LPX or co-entrapped with DOTAP in PLGA nanoparticles to form LPNs. The disposition and clearance of LPXs and LPNs in mouse lungs were studied after intratracheal administration by using single-photon emission computed tomography/computed tomography (SPECT/CT) and gamma counting. Fluorescence spectroscopy, Western blot, and confocal laser scanning microscopy were used to evaluate the silencing of the EGFP expression mediated by the LPXs and LPNs after intratracheal administration to transgenic mice expressing the EGFP gene. The in vivo biocompatibility of LPXs and LPNs was investigated by measuring the cytokine level, total cell counts in bronchoalveolar lavage fluid, and observing the lung tissue histology section. The results showed that the silencing of the EGFP expression mediated by LPNs after pulmonary administration was both prolonged and enhanced as compared to LPXs. This may be attributed to the sustained release characteristics of PLGA, and the prolonged retention in the lung tissue of the colloidally more stable LPNs in comparison to LPXs, as indicated by SPECT/CT. The presence of PLGA effectively alleviated the acute inflammatory effect of cationic lipids to the lungs. This study suggests that PLGA-based LPNs may present an effective formulation strategy to mediate sustained gene silencing effects in the lung via pulmonary administration.


Asunto(s)
Pulmón/metabolismo , Nanopartículas/química , Poliglactina 910/química , Interferencia de ARN , ARN Interferente Pequeño/administración & dosificación , Células A549 , Animales , Vías de Administración de Medicamentos , Proteínas Fluorescentes Verdes/genética , Humanos , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , ARN Interferente Pequeño/genética
14.
Int J Pharm ; 566: 32-39, 2019 Jul 20.
Artículo en Inglés | MEDLINE | ID: mdl-31077763

RESUMEN

Pulmonary delivery of small interfering RNAs (siRNAs) has shown promising results for the treatment of lung diseases with gene disorders. The aim of this work was to evaluate the effect of processing-induced thermal and shear stresses during the spray drying process on the solid-state properties, the chemical integrity and the bioactivity of spray-dried siRNA powder intended for inhalation. To this end, inhalable siRNA dry powders composed of EGFP-siRNA and mannitol were prepared by using a lab-scale spray drier. Scanning electron microscopy (SEM), laser diffraction, and X-ray powder diffraction (XRPD) were used to characterize the solid-state properties of the spray-dried siRNA-mannitol powders. High performance liquid chromatography (HPLC) and flow cytometry were exploited to assess the chemical stability and cellular transfection efficiency of siRNA formulations, respectively. The results showed that the spray-dried particles changed from spherical to irregular shape with an increase in the inlet temperature. The high inlet temperature and intensive atomization conditions resulted in more agglomerates in the spray-dried particles. XRPD analysis indicated that the presence of siRNA affected the polymorphic form of mannitol in the spray-dried powder. Compromised chemical stability and cell transfection efficiency of siRNA were observed with an increase in the thermal stress and shear stress during the spray drying process. The chemical stability of siRNA in liquid state was more prone to thermal stress when compared to the stability in the solid-state. In conclusion, stable siRNA based particles for inhalation purposes could be produced using the spray drying technology.


Asunto(s)
ARN Interferente Pequeño/química , Células A549 , Química Farmacéutica , Desecación , Estabilidad de Medicamentos , Inhaladores de Polvo Seco , Proteínas Fluorescentes Verdes/genética , Calor , Humanos , Polvos , ARN Interferente Pequeño/administración & dosificación , Estrés Mecánico
15.
Chin Med J (Engl) ; 128(21): 2887-95, 2015 Nov 05.
Artículo en Inglés | MEDLINE | ID: mdl-26521786

RESUMEN

BACKGROUND: The self-consciousness and practicality of preferentially prescribed essential medicines (EMs) are not high enough in county hospitals. The purposes of this study were to use the information-motivation-behavioral skills (IMB) model to identify the predictors of essential medicines prescribing behavior (EMPB) among doctors and to examine the association between demographic variables, IMB, and EMPB. METHODS: A cross-sectional study was carried out to assess predictive relationships among demographic variables and IMB model variables using an anonymous questionnaire administered in nine county hospitals of Anhui province. A structural equation model was constructed for the IMB model to test the instruments using analysis of moment structures 17.0. RESULTS: A total of 732 participants completed the survey. The average age of the participants was 37.7 ± 8.9 years old (range: 22-67 years old). The correct rate of information was 90.64%. The average scores of the motivation and behavioral skills were 45.46 ± 7.34 (hundred mark system: 75.77) and 19.92 ± 3.44 (hundred mark system: 79.68), respectively. Approximately half (50.8%) of respondents reported that the proportion of EM prescription was below 60%. The final revised model indicated a good fit to the data (χ2 /df = 4.146, goodness of fit index = 0.948, comparative fit index = 0.938, root mean square error of approximation = 0.066). More work experience (ß = 0.153, P < 0.001) and behavioral skills (ß = 0.449, P < 0.001) predicted more EMPB. Higher income predicted less information (ß = -0.197, P < 0.001) and motivation (ß = -0.204, P < 0.001). Behavioral skills were positively predicted by information (ß = 0.135, P < 0.001) and motivation (ß = 0.742, P < 0.001). CONCLUSION: The present study predicted some factors of EMPB, and specified the relationships among the model variables. The utilization rate of EM was not high enough. Motivation and behavior skills were crucial factors affecting EMPB. The influence of demographic variables, such as income and work experience, on EMPB should be fully appreciated. Comprehensive intervention measures should be implemented from multiple perspectives.


Asunto(s)
Pautas de la Práctica en Medicina/estadística & datos numéricos , Adulto , Anciano , China , Estudios Transversales , Femenino , Hospitales de Condado/estadística & datos numéricos , Humanos , Masculino , Persona de Mediana Edad
17.
BMC Health Serv Res ; 15: 403, 2015 Sep 22.
Artículo en Inglés | MEDLINE | ID: mdl-26394615

RESUMEN

BACKGROUND: In August 2009, China formally established the National Essential Medicines System (NEMS) and implemented this system in the government-funded primary care medical and health institutions. After nearly four years of practice, the system has already been generalized to the county-level public hospitals. This study aimed to examine the impact on the operation of the hospitals through implementing the NEMS in Anhui Province and put forward some improvement measures. METHODS: For quantitative analyses, we distributed 21 questionnaires to 21 county-level public hospitals in Anhui Province, which had implemented the national public hospital reform. Twenty valid questionnaires were returned, response rate was 95.2 %. Questions covered storage, usage and supply of essential medicines, compensation mechanisms, insurance policies, hospital incomes, service amounts and fees from January to June in each of the years from 2011 to 2013. For qualitative study, we chose three from 21 hospitals based on geographical distribution and conducted focus group interviews based on a planned interview outline centered on the implementation status of the system. RESULTS: Following implementation, the types of essential medicines stocked and the proportion of total sales that were composed of essential medicines have increased but do not yet meet the required standards issued in the government document, which was not less than 95 % and 30 % of the total, respectively. The average financial subsidies had increased by 1,665,200 yuan, and significant increases appeared in provincial financial assistance. The average inpatient fees per visit decreased by 487.41 yuan. Increases in income from medicines during hospitalization led to increases in per-visit hospitalization fees. Unexpectedly, higher financial assistance revenue also led to higher average per-visit hospitalization fees. DISCUSSION: The guiding role of the National Essential Medicines List remains to be reinforced, and specific lists for county hospitals should be developed. Supervision was required to implement the process of guaranteeing the storage and usage of essential medicines. The compensation mechanism was far from sound, and the leverage of the health insurance policies was not obvious. Regarding the reductions in the proportion of income derived from medicines and per-visit inpatient fees, the policy had been partially successful. CONCLUSIONS: Our results showed that the implementation of the Essential Medicines System do have a beneficial role in the reduction of the drug fees and further alleviates the burden of the masses. Much effort should be made to the redesign of the compensation mechanism, mainly including the government and the medical insurance compensation, emphasizing on both the fairness and the rationality of the compensation in the future.


Asunto(s)
Medicamentos Esenciales/provisión & distribución , Accesibilidad a los Servicios de Salud , Hospitales Públicos , China , Honorarios y Precios , Grupos Focales , Reforma de la Atención de Salud/economía , Política de Salud/economía , Hospitales Públicos/economía , Humanos , Renta , Seguro de Salud/economía , Entrevistas como Asunto , Evaluación de Programas y Proyectos de Salud , Investigación Cualitativa , Encuestas y Cuestionarios
18.
PLoS One ; 10(8): e0135782, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26275301

RESUMEN

BACKGROUND: The high prevalence of risky irrational drug use behaviors mean that outpatients face high risks of drug resistance and even death. This study represents the first application of the Information-Motivation-Behavioral Skills (IMB) model on rational drug use behavior among second-level hospital outpatients from three prefecture-level cities in Anhui, China. Using the IMB model, our study examined predictors of rational drug use behavior and determined the associations between the model constructs. METHODS: This study was conducted with a sample of 1,214 outpatients aged 18 years and older in Anhui second-level hospitals and applied the structural equation model (SEM) to test predictive relations among the IMB model variables related to rational drug use behavior. RESULTS: Age, information and motivation had significant direct effects on rational drug use behavior. Behavioral skills as an intermediate variable also significantly predicted more rational drug use behavior. Female gender, higher educational level, more information and more motivation predicted more behavioral skills. In addition, there were significant indirect impacts on rational drug use behavior mediated through behavioral skills. CONCLUSIONS: The IMB-based model explained the relationships between the constructs and rational drug use behavior of outpatients in detail, and it suggests that future interventions among second-level hospital outpatients should consider demographic characteristics and should focus on improving motivation and behavioral skills in addition to the publicity of knowledge.


Asunto(s)
Modelos Psicológicos , Motivación , Pacientes Ambulatorios , Asunción de Riesgos , Adulto , China , Femenino , Humanos , Masculino , Persona de Mediana Edad
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