Performance of ChatGPT Across Different Versions in Medical Licensing Examinations Worldwide: Systematic Review and Meta-Analysis.

BACKGROUND: Over the past 2 years, researchers have used various medical licensing examinations to test whether ChatGPT (OpenAI) possesses accurate medical knowledge. The performance of each version of ChatGPT on the medical licensing examination in multiple environments showed remarkable differences. At this stage, there is still a lack of a comprehensive understanding of the variability in ChatGPT's performance on different medical licensing examinations. OBJECTIVE: In this study, we reviewed all studies on ChatGPT performance in medical licensing examinations up to March 2024. This review aims to contribute to the evolving discourse on artificial intelligence (AI) in medical education by providing a comprehensive analysis of the performance of ChatGPT in various environments. The insights gained from this systematic review will guide educators, policymakers, and technical experts to effectively and judiciously use AI in medical education. METHODS: We searched the literature published between January 1, 2022, and March 29, 2024, by searching query strings in Web of Science, PubMed, and Scopus. Two authors screened the literature according to the inclusion and exclusion criteria, extracted data, and independently assessed the quality of the literature concerning Quality Assessment of Diagnostic Accuracy Studies-2. We conducted both qualitative and quantitative analyses. RESULTS: A total of 45 studies on the performance of different versions of ChatGPT in medical licensing examinations were included in this study. GPT-4 achieved an overall accuracy rate of 81% (95% CI 78-84; P<.01), significantly surpassing the 58% (95% CI 53-63; P<.01) accuracy rate of GPT-3.5. GPT-4 passed the medical examinations in 26 of 29 cases, outperforming the average scores of medical students in 13 of 17 cases. Translating the examination questions into English improved GPT-3.5's performance but did not affect GPT-4. GPT-3.5 showed no difference in performance between examinations from English-speaking and non-English-speaking countries (P=.72), but GPT-4 performed better on examinations from English-speaking countries significantly (P=.02). Any type of prompt could significantly improve GPT-3.5's (P=.03) and GPT-4's (P<.01) performance. GPT-3.5 performed better on short-text questions than on long-text questions. The difficulty of the questions affected the performance of GPT-3.5 and GPT-4. In image-based multiple-choice questions (MCQs), ChatGPT's accuracy rate ranges from 13.1% to 100%. ChatGPT performed significantly worse on open-ended questions than on MCQs. CONCLUSIONS: GPT-4 demonstrates considerable potential for future use in medical education. However, due to its insufficient accuracy, inconsistent performance, and the challenges posed by differing medical policies and knowledge across countries, GPT-4 is not yet suitable for use in medical education. TRIAL REGISTRATION: PROSPERO CRD42024506687; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=506687.

Multiphase Symbiotic Engineered Elastic Ceramic-Carbon Aerogels with Advanced Thermal Protection in Extreme Oxidative Environments.

Elastic aerogels can dissipate aerodynamic forces and thermal stresses by reversible slipping or deforming to avoid sudden failure caused by stress concentration, making them the most promising candidates for thermal protection in aerospace applications. However, existing elastic aerogels face difficulties achieving reliable protection above 1500 °C in aerobic environments due to their poor thermomechanical stability and significantly increased thermal conductivity at elevated temperatures. Here, a multiphase sequence and multiscale structural engineering strategy is proposed to synthesize mullite-carbon hybrid nanofibrous aerogels. The heterogeneous symbiotic effect between components simultaneously inhibits ceramic crystalline coarsening and carbon thermal etching, thus ensuring the thermal stability of the nanofiber building blocks. Efficient load transfer and high interfacial thermal resistance at crystalline-amorphous phase boundaries on the microscopic scale, coupled with mesoscale lamellar cellular and locally closed-pore structures, achieve rapid stress dissipation and thermal energy attenuation in aerogels. This robust thermal protection material system is compatible with ultralight density (30 mg cm-3), reversible compression strain of 60%, extraordinary thermomechanical stability (up to 1600 °C in oxidative environments), and ultralow thermal conductivity (50.58 mW m-1 K-1 at 300 °C), offering new options and possibilities to cope with the harsh operating environments faced by space exploration.

Narrowing row spacing and adding inter-block promote the grain filling and flag leaf photosynthetic rate of wheat under enlarged drip tube spacing system.

Enlarging the lateral space of drip tubes saves irrigation equipment costs (drip tubes and bypass), but it will lead to an increased risk of grain yield heterogeneity between wheat rows. Adjusting wheat row spacing is an effective cultivation measure to regulate a row's yield heterogeneity. During a 2-year field experiment, we investigated the variations in yield traits and photosynthetic physiology by utilizing two different water- and fertilizer-demanding spring wheat cultivars (NS22 and NS44) under four kinds of drip irrigation patterns with different drip tube lateral spacing and wheat row spacing [① TR4, drip tube spacing (DTS) was 60 cm, wheat row horizontal spacing (WRHS) was 15 cm; ② TR6, DTS was 90 cm, WRHS was 15 cm; ③ TR6L, DTS was 90 cm, WRHS was 10 cm, inter-block spacing (IBS) was 35 cm; and ④ TR6S, DTS was 80 cm, WRHS was 10 cm, IBS was 25 cm]. The results showed that under 15-cm equal row spacing condition, after the number of wheat rows served by a single tube increased from four (TR4, control) to six (TR6), NS22 and NS44 exhibited a marked decline in yield. The decline of NS22 (9.93%) was higher than that of NS44 (9.04%), and both cultivars also showed a greater decrease in grain weight and average grain-filling rate (AGFR) of inferior grains (NS22: 23.19%, 13.97%; NS44: 7.78%, 5.86%) than the superior grains (NS22: 10.60%, 8.33%; NS44: 4.89%, 4.62%). After the TR6 was processed to narrow WRHS (from 15 to 10 cm) and add IBS (TR6L: 35 cm; TR6S: 25 cm), the grain weight per panicle (GWP) and AGFR of superior and inferior grains in the third wheat row (RW3) of NS22 and NS44 under TR6L increased significantly by 26.05%, 8.22%, 14.05%, 10.50%, 5.09%, and 5.01%, respectively, and under TR6S, they significantly increased by 20.78%, 9.91%, 16.19%, 9.28%, 5.01%, and 4.14%, respectively. The increase in GWP and AGFR was related to the increase in flag leaf area, net photosynthetic rate, chlorophyll content, relative water content, actual photochemical efficiency of PSII, and photochemical quenching coefficient. Among TR4, TR6, TR6L, and TR6S, for both NS22 and NS44, the yield of TR6S was significantly higher than that of TR6 and TR6L. Furthermore, TR6S showed the highest economic benefit.

Fabrication and Application of Ag@SiO2/Au Core-Shell SERS Composite in Detecting Cu2+ in Water Environment.

A sensitive and simple method for detecting Cu2+ in the water source was proposed by using surface-enhanced Raman scattering spectroscopy (SERS) based on the Ag@SiO2/Au core-shell composite. The Ag@SiO2 SERS tag was synthesized by a simple approach, in which Ag nanoparticles were first embedded with Raman reporter PATP and next coated with a SiO2 shell. The Ag@SiO2 nanoparticles had strong stability even in a high-concentration salty solution, and there were no changes to their properties and appearance within one month. The Ag@SiO2/Au composite was fabricated through a controllable self-assemble process. L-cysteine was decorated on the surface of a functionalized Ag@SiO2/Au composite, as the amino and carboxyl groups of it can form coordinate covalent bond with Cu2+, which shows that the Ag@SiO2/Au composite labelled with L-cysteine has excellent performance for the detection of Cu2+ in aqueous media. In this study, the SERS detection of Cu2+ was carried out using Ag@SiO2 nanoparticles, and the limit of detection (LOD) as low as 0.1 mg/L was achieved.

Multiscale Interpenetrated/Interconnected Network Design Confers All-Carbon Aerogels with Unprecedented Thermomechanical Properties for Thermal Insulation under Extreme Environments.

With ultralight weight, low thermal conductivity, and extraordinary high-temperature resistance, carbon aerogels hold tremendous potential against severe thermal threats encountered by hypersonic vehicles during the in-orbit operation and re-entry process. However, current 3D aerogels are plagued by irreconcilable contradictions between adiabatic and mechanical performance due to monotonicity of the building blocks or uncontrollable assembly behavior. Herein, a spatially confined assembly strategy of multiscale low-dimensional nanocarbons is reported to decouple the stress and heat transfer. The nanofiber framework, a basis for transferring the loading strain, is covered by a continuous thin-film-like layer formed by the aggregation of nanoparticles, which in combination serve as the fundamental structural units for generating an elastic behavior while yielding compartments in aerogels to suppress the gaseous fluid thermal diffusion within distinct partitions. The resulting all-carbon aerogels with a hierarchical cellular structure and quasi-closed cell walls achieve the best thermomechanical and insulation trade-off, exhibiting flyweight density (24 mg cm-3 ), temperature-constant compressibility (-196-1600 °C), and a low thermal conductivity of 0.04 829 W m-1 K-1 at 300 °C. This strategy provides a remarkable thermal protection material in hostile environments for future aerospace exploration.

Way to a Library of Ti-Series Oxide Nanofiber Sponges that are Highly Stretchable, Compressible, and Bendable.

Ti-series oxide ceramics in the form of aerogels, such as TiO2, SrTiO3, BaTiO3, and CaCu3Ti4O12, hold tremendous potential as functional materials owing to their excellent optical, dielectric, and catalytic properties. Unfortunately, these inorganic aerogels are usually brittle and prone to pulverization owing to weak inter-particulate interactions, resulting in restricted application performance and serious health risks. Herein, a novel strategy is reported to synthesize an elastic form of an aerogel-like, highly porous structure, in which activity-switchable Ti-series oxide sols transform from the metastable state to the active state during electrospinning, resulting in condensation and solidification at the whipping stage to obtain curled nanofibers. These curled nanofibers are further entangled when flying in the air to form a physically interlocked, elastic network mimicking the microstructure of high-elasticity hydrogels. This strategy provides a library of Ti-series oxide nanofiber sponges with unprecedented stretchability, compressibility, and bendability, possessing extensive opportunities for greener, safer, and broader applications as integrated or wearable functional devices. As a proof-of-concept demonstration, a new, elastic form of TiO2, composed of both "white" and "black" TiO2 nanofiber sponges, is constructed as spontaneous air-conditioning textiles in smart clothing, buildings, and vehicles, with unique bidirectional regulation of radiative cooling in summer and solar heating in winter.

Phthalate acid esters contribute to the cytotoxicity of mask leachate: Cell-based assay for toxicity assessment.

After the COVID-19 outbreak, masks have become an essential part of people lives. Although several studies have been conducted to determine the release of hazardous substances from masks, how their co-presence poses a potential exposure risk to human health remains unexplored. In this study, we quantitatively compared the leaching of substances from six different common types of masks, including phthalate acid esters (PAEs), metals, and microplastics (MPs), and comprehensively evaluated the potential cytotoxicity of different leachates. MPs smaller than 3 µm were quantified by Py-GC-MS, and reusable masks showed greater releasing potentials up to 1504 µg/g. We also detected the prevalence of PAEs in masks, with the highest release reaching 42 µg/g, with dibutyl phthalate (DBP), diisobutyl phthalate (DiBP) and bis (2-ethylhexyl) phthalate (DEHP) being the predominant types. Moreover, the antimicrobial cloth masks released 173.0 µg of Cu or 4.5 µg of Ag, representing 2.7% and 0.04% of the original masks, respectively. Our cell-based assay results demonstrated for the first time that mask leachate induced nuclear condensation with DNA damage, and simultaneously triggered high levels of glutathione and reactive oxidative stress production, which exacerbated mitochondrial fragmentation, eventually leading to cell death. Combined with substance identification and correlation analysis, PAEs were found to be the contributors to cytotoxicity. Masks containing Cu or Ag led to acidification of lysosomes and alkalinization of cells. These results strongly suggested that the levels of PAEs in the production of regulatory masks should be strictly controlled.

Transmission and retention of antibiotic resistance genes (ARGs) in chicken and sheep manure composting.

Transmission of ARGs during composting with different feedstocks (i.e., sheep manure (SM), chicken manure (CM) and mixed manure (MM, SM:CM = 3:1 ratio) was studied by metagenomic sequencing. 53 subtypes of ARGs for 22 types of antibiotics were identified as commonly present in these compost mixes; among them, CM had higher abundance of ARGs, 1.69 times than that in SM, while the whole elimination rate of CM, MM and SM were 55.2%, 54.7% and 42.9%, respectively. More than 50 subtypes of ARGs (with 8.6%, 11.4% and 20.9% abundance in the initial stage in CM, MM and SM composting) were "diehard" ARGs, and their abundance grew significantly to 56.5%, 63.2% and 69.9% at the mature stage. These "diehard" ARGs were transferred from initial hosts of pathogenic and/or probiotic bacteria to final hosts of thermophilic bacteria, by horizontal gene transfer (HGT) via mobile gene elements (MGEs), and became rooted in composting products.

Effect of Physical Activity/Exercise on Cardiorespiratory Fitness in Children and Adolescents with Type 1 Diabetes: A Scoping Review.

The most common type of diabetes among children and adolescents is type 1 diabetes mellitus (T1DM), which is associated with an increased risk of cardiovascular disease (CVD). Additionally, lower levels of cardiorespiratory fitness (CRF) are linked to an increased risk of CVD. Regular exercise is associated with a decreased risk of CVD and improved CRF. We conducted this scoping review to assess the effects of exercise on CRF in youth with T1DM. Three electronic databases (PubMed, Embase, and Cochrane Central Register of Controlled Trials) were used to search for the relevant literature. In this analysis, the PICOS method was used to select studies and was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Guidelines scoping review guidelines for the evaluation of the effects of physical activity and cardiac function; the criteria may include the type and intensity of physical activity, the duration of the intervention, peak oxygen consumption (VO2), peak minute ventilation (VE), and peak heart rate of cardiorespiratory fitness. Screening resulted in 434 records. Of these, nine articles were included in our study. These nine studies were experimental (noncontrolled trials or randomized controlled trials) (n = 7) and observational (cross-sectional) (n = 2), and could be used to evaluate the effectiveness of physical activity interventions on cardiac function. The effects of exercise on CRF in youth with T1DM vary according to the type, frequency, and intensity of the exercise. According to our review, the duration of exercise included in the studies did not meet the recommendations of the guidelines for youth with T1DM. Additionally, half of the studies revealed that exercise could optimize the lipid profile in youth with T1DM. Hence, this research is to provide an overview of the effects of physical activity and exercise on CRF, cardiovascular fitness, lipid profile, and blood pressure in youth with T1DM, as well as identified potential limitations of the existing studies. Nevertheless, the limited number of clinical studies employing exercise interventions for children and adolescents with T1DM emphasize the need for more studies in this area, and more specific modes of exercise should be developed in the future.

Nutritional risk factors for all-cause mortality of critically ill patients: a retrospective cohort study.

OBJECTIVES: This study aimed to explore the predictive value of single and multiple risk factors for the clinical outcomes of critically ill patients receiving enteral nutrition and to establish an effective evaluation model. DESIGN: Retrospective cohort study. SETTING: Data from the 2020-2021 period were collected from the electronic records of the First Affiliated Hospital, Nanjing Medical University. PARTICIPANTS: 459 critically ill patients with enteral nutrition in the geriatric intensive care unit were included in the study. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was 28-day mortality. The secondary outcomes were 28-day invasive mechanical ventilation time, intensive care unit stay, Nutrition Risk Screening 2002 (NRS2002) score and Acute Physiology and Chronic Health Evaluation II (APACHE II) score. RESULTS: Independent prognostic factors, including prealbumin/procalcitonin (PCT) ratio and APACHE II score, were identified using a logistic regression model and used in the nomogram. The area under the receiver operating characteristic curve and concordance index indicated that the predictive capacity of the model was 0.753. Moreover, both the prealbumin/PCT ratio and the combination model of PCT, prealbumin and NRS2002 had a higher predictive value for clinical outcomes. Subgroup analysis also identified that a higher inflammatory state (PCT >0.5 ng/mL) and major nutritional risk (NRS2002 >3) led to worse clinical outcomes. In addition, patients on whole protein formulae bore less nutritional risk than those on short peptide formulae. CONCLUSIONS: This nomogram had a good predictive value for 28-day mortality in critically ill patients receiving enteral nutrition. Both the prealbumin/PCT ratio and the combination model (PCT, prealbumin and NRS2002), as composite models of inflammation and nutrition, could better predict the prognosis of critically ill patients.

Feedstock-dependent abundance of functional genes related to nitrogen transformation controlled nitrogen loss in composting.

The objective of this work was to explore how selection of feedstock affects nitrogen cycle genes during composting, which eventually determines the nitrogen loss. Four composting mixes (CM: chicken manure; SM: sheep manure; MM1/3: mixed manure with CM: SM = 1:3 w/w, MM3/1: CM: SM = 3:1 w/w) were investigated. Results showed that adding 25 % and 75 % SM to CM reduced 26.5 % and 57.9 % nitrogen loss, respectively. CM contained more ammonification genes and nrfA gene, while SM had more denitrification genes. Nitrogen fixation genes in CM were slightly higher than that in SM at the initial stage, but they sharply dropped off as the composting entered the high temperature stage. MM1/3 showed significantly reduced ammonification genes than CM, and increased nitrogen fixation and NH4+ assimilation genes. Therefore, adding SM to CM could change the abundance of genes and enzymes related to nitrogen cycle to reduce nitrogen loss.

Genetic Mapping and Analysis of a Compact Plant Architecture and Precocious Mutant in Upland Cotton.

With the promotion and popularization of machine cotton-picking, more and more attention has been paid to the selection of early-maturity varieties with compact plant architecture. The type of fruit branch is one of the most important factors affecting plant architecture and early maturity of cotton. Heredity analysis of the cotton fruit branch is beneficial to the breeding of machine-picked cotton. Phenotype analysis showed that the types of fruit branches in cotton are controlled by a single recessive gene. Using an F2 population crossed with Huaxin102 (normal branch) and 04N-11 (nulliplex branch), BSA (Bulked Segregant Analysis) resequencing analysis and GhNB gene cloning in 04N-11, and allelic testing, showed that fruit branch type was controlled by the GhNB gene, located on chromosome D07. Ghnb5, a new recessive genotype of GhNB, was found in 04N-11. Through candidate gene association analysis, SNP 20_15811516_SNV was found to be associated with plant architecture and early maturity in the Xinjiang natural population. The GhNB gene, which is related to early maturity and the plant architecture of cotton, is a branch-type gene of cotton. The 20_15811516_SNV marker, obtained from the Xinjiang natural population, was used for the assisted breeding of machine-picked cotton varieties.

Additives improved saprotrophic fungi for formation of humic acids in chicken manure and corn stover mix composting.

The objective of this study was to analyze the effects of additives (biochar (BC) and palygorskite (PG)) on predominant fungi succession throughout composting of corn stover/chicken manure mix to influence humic substances formation (HS). Results indicated that BC and PG promoted the polymerization of HS and formation of more humic acids (HA), and BC performed better than PG, 10% additive was better than 5%. ITS rRNA gene sequencing showed that predominant fungi succession was significantly affected by BC and PG in composting, correlation between HS formation and predominant fungi indicated that BC and PG boosted lignocellulose-degrading fungi which could break down fulvic acids (FA) and HM to form more HA. Fungi function analysis showed that 10% BC significantly increased saprotrophic fungi, and decreased pathogenic fungi. Therefore, addition of 10% BC was conductive to promote the formation of HA and improve compost quality.

Typhoon-induced turbulence redistributed microplastics in coastal areas and reformed plastisphere community.

The increasing microplastic pollution together with the plastisphere-associated ecological threats in coastal areas have aroused global concern. Tropical cyclones have been increased in both frequency and intensity under global warming, causing intense impact on the microplastics distribution and the structure of coastal ecosystems. However, until most currently, the extent to which typhoon impacts the microplastics and plastisphere community remains poorly known. This study analyzed the effects of Typhoon Wipha (Code: 1907) on microplastics abundance and composition in surface water and sediment crossed coastal areas of Shenzhen. Here we found a significant typhoon-induced increase in microplastics abundance in surface water, whereas an opposite trend was observed in sediment. Despite the evident transportation of microplastics from sediment to surface water by agitation, a possible microplastics influx was introduced by typhoon as evidenced by the large attribution of unknown force in source tracking analysis. Furthermore, typhoon had adeptly uniformed the plastisphere community in the sediment along the 190 km costal line overnight. A significant increase of nitrogen fixer, Bradyrhizobiaceae, was observed ubiquitously after typhoon, which might alter the nitrogen cycling and increase eutrophic condition of the coastal ecological system. Together, this study expanded the knowledge about the impact of typhoon-induced influx of the microplastics on coastal biogeochemical cycling. Moreover, the microplastics and the plastisphere compositional pattern revealed here will underpin future studies on adsorption behavior, interfacial processes and ecotoxicity of the coastal microplastic pollution.

Visible-Light-Driven and Self-Hydrogen-Donated Nanofibers Enable Rapid-Deployable Antimicrobial Bioprotection.

The novel coronavirus SARS-CoV-2 has prompted a worldwide pandemic and poses a great threat to public safety and global economies. Most present personal protective equipment (PPE) used to intercept pathogenic microorganisms is deficient in biocidal properties. Herein, we present green nanofibers with effective antibacterial and antiviral activities that can provide sustainable bioprotection by continuously producing reactive oxygen species (ROS). The superiority of the design is that the nanofibers can absorb and store visible light energy and maintain the activity under light or dark environment. Moreover, the nanofibers can uninterruptedly release ROS in the absence of an external hydrogen donor, acting as a biocide under all weather conditions. A facile spraying method is proposed to rapidly deploy the functional nanofibers to existing PPE, such as protective suits and masks. The modified PPE exhibit stable ROS production, excellent capacity for storing activity potential, long-term durability, and high bactericidal (>99.9%) and viricidal (>99.999%) efficacies.

Measurements of formation cross-sections of short-lived nuclei around the 14 MeV neutron induced reactions on 180Hf and 90Zr and theoretical calculation of excitation functions.

The cross sections of the 180Hf(n,p)180Lu and 90Zr(n,2n)89mZr reactions were measured around the neutron energies of 13.5-14.8 MeV by using the activation technique. The excitation functions of the above reactions in the neutron energies from the threshold to 20 MeV were calculated by using the nuclear theoretical model program system Talys-1.9 with the adjusted relevant parameters. The measured results were discussed and compared with previous experiments by other researchers and with the evaluated data of ENDF/B-VIII.0, CENDL-3.1, JEFF-3.3, JENDL-4.0u2, BROND-3.1 as well as the theoretical values based on Talys-1.9. The obtained experimental values at some neutron energies, within experimental error, are consistent with those of the fitting line of the results of previous experiments and are also consistent with those of theoretical excitation curve at the corresponding energies. The obtained theoretical excitation curves match well with most of the experimental data.

Determination of Environmental Micro(Nano)Plastics by Matrix-Assisted Laser Desorption/Ionization-Time-of-Flight Mass Spectrometry.

Micro(nano)plastics (MNPs) are widely acknowledged as global environmental threat while determination methods for MNPs are still lacking and becoming a growing concern. This study provides a novel method for MNPs identification/quantification by matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry (MALDI-TOF MS). Factors affecting the measurement were optimized, including laser energy, matrix (M), analyte (A), cationization agent (C), and MAC volume ratio. Under the optimal conditions, the peaks representative of polystyrene (PS) and polyethylene terephthalate (PET) were identified, and the mass differences were consistent with the molecular weight of the corresponding oligomer. A quantitative correlation was built between normalized signal intensity and ln[polymer concentration] with a correlation coefficient above 0.96 for low-molecular-weight polymers and 0.98 for high-molecular-weight polymers. Furthermore, two types of environmental MNP samples were prepared, including aviation cup particles as fresh plastics and aged MNPs extracted from river sediment. By using MALDI-TOF MS, the PS-related MNPs (in both aviation cup and sediment) consisted of C8H8 and C16H16O oligomers, while the PET-related MNPs (only found in sediment) were identified with repeated units of C10H8O4 and C12H12O4. According to the quantitative correlation curve, the contents of PS and PET MNPs were quantified as 8.56 ± 0.04 and 28.71 ± 0.20 mg·kg-1, respectively, in the collected sediment. This study is the first attempt to propose a quantification method with the employment of MALDI-TOF MS for aged MNPs analysis in environmental samples, which can not only supply an effective method for MNP analysis but also inspire future studies on the in situ distribution and transformation of MNPs in environmental and biological samples.

In vitro effect of ulipristal acetate on human sperm parameters and function.

To observe and investigate the in vitro effect of ulipristal acetate (UPA) on human sperm parameters and function. The 20 patients with normal semen parameters and average age of (32.5±8.5) years old, who were treated in our hospital from January 2018 to August 2018, were selected as research objects. They were subjected to density gradient centrifugation, and then four groups were incubated for about an hour in a culture medium containing different concentrates of ulipristal acetate and the other two groups were set as blank control group and dimethylsulphoxide (DMSO) control group. Indicators including sperm motility, sperm hyperactivation and sperm concentration of free calcium ions of each group were tested. Under the ulipristal acetate concentration of 0.0.4 mol/L, the proportion of sperm damage was increased, the length of tail was increased, and the proportion of sperm hyperactivation was decreased, p<0.05. In addition, the acrosome reaction was inhibited, which significantly reduced the calcium concentration in the sperm, p<0.05. Ulipristal acetate can significantly inhibit acrosome reaction and hyperactivation of sperm in vitro, and can reduce the concentration of calcium ions in sperm, thus causing sperm damage.

Model drug as pore former for controlled release of water-soluble metoprolol succinate from ethylcellulose-coated pellets without lag phase: opportunities and challenges.

The objective of the present study was to evaluate the feasibility of using model drug metoprolol succinate (MS) as a pore former to modify the initial lag phase (i.e., a slow or non-release phase in the first 1-2 h) associated with the drug release from coated pellets. MS-layered cores with high drug-layering efficiency (97% w/w) were first prepared by spraying a highly concentrated drug aqueous solution (60% w/w, 70°C) on non-pareils without using other binders. The presence of MS in ethylcellulose (EC) coating solution significantly improved the coating process by reducing pellets sticking, which often occurs during organic coating. There may be a maximum physical compatibility of MS with EC, and the physical state of the drug in the functional coating layer of EC/MS (80:20) was simultaneously crystalline and non-crystalline (amorphous or solid molecule solution). The lag phase associated with hydroxypropylcellulose (HPC) as a pore former was not observed when MS was used as a pore former. The drug release from EC/MS-coated pellets was pH independent, inversely proportional to the coating levels, and directly related to the pore former levels. The functional coating layer with MS as a pore former was not completely stabilized without curing. Curing at 60°C for 1 day could substantially improve the stability of EC/MS-coated pellets. The physical state of the drug in the free film of EC/MS (85:15) changed partially from amorphous to crystal when cured at 60°C for 1 day, which should be attributed to the incompatibility of the drug with EC.