A longitudinal study on the effect of labor values on benign/malicious envy: the mindfulness reperceiving model.

This study investigates the relationship between labor values and two forms of envy-benign and malicious-as well as the potential mediating role of mindfulness using a mindfulness reperceiving model. Two thousand three hundred sixty three Chinese teenagers participated in a longitudinal study over an eight-month period, completing questionnaires measuring labor values, benign envy, malicious envy, and mindfulness. The cross-sectional data showed that labor values had an immediate negative effect on malicious envy, with mindfulness partially mediating this relationship. Additionally, labor values had an immediate positive effect on benign envy, but mindfulness did not mediate this relationship. Longitudinal data analysis revealed that the delayed effect of labor values on later benign/malicious envy was similar to its immediate effect. However, mindfulness only played a mediating role in the relationship between labor values and later malicious envy. Cross-gender stability was found in both the immediate effect model and the delayed effect model. Overall, this study sheds light on the influence of labor values on the development of social emotions and the potential mediating role of mindfulness in the Chinese cultural context.

Application of telemedicine system for older adults postoperative patients in community: a feasibility study.

Purpose: In response to the growing challenges posed by an aging society, a telemedicine system was developed specifically for older adults postoperative patients, and its effectiveness was thoroughly investigated. Methods: Between May 2020 and May 2022, a total of 88 older adults postoperative patients were enrolled and randomly allocated into an experimental group and a control group. The experimental group received telemedicine services after discharge, while the control group received conventional medical services following the traditional protocol. One month after discharge, various indicators were evaluated for both groups, including number of visits, medical expenditures, postoperative recovery, anxiety, depression and satisfaction. Results: The number of visits and medical expenditures of the experimental group were less than those of the control group [1 (0, 1) vs. 1 (1, 2), Z = -3.977, p < 0.001; 25.25 (0.00, 277.40) yuan vs. 174.65 (49.63, 446.10) yuan, Z = -2.150, p = 0.032]. In both groups, there were 2 cases of incision infection, respectively. No significant difference was observed between the two groups (Fisher χ2, p = 0.259). In both groups, there was no instance of incision bleeding, incision dehiscence, readmission, or reoperation. Additionally, there was no significant difference in physical status between the two groups at discharge and after discharge (66.06 ± 8.92 vs. 65.45 ± 7.39 t = 0.287, p = 0.775; 73.33 ± 9.97 vs. 70.91 ± 7.50, t = 1.202, p = 0.235). And there was no significant difference in the change of physical status between the two groups after discharge [10.00 (0.00, 10.00) vs. 5.00 (0.00, 10.00), Z = -1.077, p = 0.281]. There was no significant difference in body weight change between the two groups after discharge [1.05 (0.38, 1.60) Kg vs. 0.80 (0.50, 1.43) Kg, Z = -0.265, p = 0.791]. There was no significant difference in the levels of anxiety and depression between the two groups at discharge (45.64 ± 8.10 vs. 44.60 ± 8.24, t = 0.520, p = 0.604, 48.33 ± 8.46 vs. 47.50 ± 6.85, t = 0.418, p = 0.677). But the levels of anxiety and depression in the experimental group were lower than those in the control group after discharge (34.92 ± 7.38 vs. 39.03 ± 8.42, t = -2.183, p = 0.032, 37.86 ± 7.29 vs. 41.93 ± 7.13, t = -2.281, p = 0.025); The change of anxiety level and depression level of the experimental group were more than those of the control group [-10.00 (-11.25, -8.75) vs. -5.00 (-7.81, -3.75), Z = -5.277, p < 0.001; -10.00 (-12.50, -7.50) vs. -5.00 (-7.75, -3.44), Z = -4.596, p < 0.001]. The level of satisfaction regarding medical services, daily care, and psychological comfort was higher in the experimental group compared to the control group [3 (3, 3.25) vs. 2 (1, 2), Z = -5.931, p < 0.001; 3 (3, 4) vs. 3 (2, 3), Z = -2.286, p = 0.022; 2 (1, 3) vs. 1 (0.75, 2), Z = -2.081, p = 0.037]. Conclusion: In the context of an aging society, telemedicine system can offer improved healthcare to older adults postoperative patients. This includes benefits such as reducing number of visits, saving medical expenditures, enhancing psychological comfort and daily care.

Experimental study on the effect and mechanism of adipose stem cell-derived exosomes combined with botulinum toxin A on skin trauma in rats.

BACKGROUND: Adipose stem cell-derived exosomes (ADSC-EXO) and botulinum toxin type A (BTX-A) individually showed a therapeutic effect on skin wound repair. AIMS: This study investigated their synergistic effect on promoting skin wound healing in vitro and in vivo and the underlying molecular events. METHODS: ADSCs were isolated from Sprague-Dawley (SD) rats to obtain ADSC-EXO by ultrafiltration and ultracentrifugation and were confirmed using nanoparticle tracking analysis and transmission electron microscopy. Human skin fibroblasts (HSF) were cultured and treated with or without ADSC-EXO, BTX-A, or their combination. Changes in cell phenotypes and protein expression were analyzed using different in vitro assays, and a rat skin wound model was used to assess their in vivo effects. RESULTS: The isolated ADSC-EXO from primarily cultured ADSCs had a circular vesicle shape with a 30-180 nm diameter. Treatment of HSF with ADSC-EXO and/or BTX-A significantly accelerated HSF migration in vitro and skin wound healing in a rat model. Moreover, ADSC-EXO plus BTX-A treatment dramatically induced VEGFA expression but reduced COL III and COL I levels in vivo. ADSC-EXO and/or BTX-A treatment significantly upregulated TGF-ß3 expression on Day 16 after surgery but downregulated TGF-ß1 expression, suggesting that ADSC-EXO plus BTX-A promoted skin wound healing and reduced inflammatory cell infiltration. CONCLUSIONS: The ADSC-EXO plus BTX-A treatment demonstrated a synergistic effect on skin wound healing through upregulation of VEGF expression and the TGF-ß3/TGF-ß1 and COL III/COL I ratio.

Sleep deprivation attenuates neural responses to outcomes from risky decision-making.

Sleep loss impacts a broad range of brain and cognitive functions. However, how sleep deprivation affects risky decision-making remains inconclusive. This study used functional MRI to examine the impact of one night of total sleep deprivation (TSD) on risky decision-making behavior and the underlying brain responses in healthy adults. In this study, we analyzed data from N = 56 participants in a strictly controlled 5-day and 4-night in-laboratory study using a modified Balloon Analogue Risk Task. Participants completed two scan sessions in counter-balanced order, including one scan during rested wakefulness (RW) and another scan after one night of TSD. Results showed no differences in participants' risk-taking propensity and risk-induced activation between RW and TSD. However, participants showed significantly reduced neural activity in the anterior cingulate cortex and bilateral insula for loss outcomes, and in bilateral putamen for win outcomes during TSD compared with RW. Moreover, risk-induced activation in the insula negatively correlated with participants' risk-taking propensity during RW, while no such correlations were observed after TSD. These findings suggest that sleep loss may impact risky decision-making by attenuating neural responses to decision outcomes and impairing brain-behavior associations.

Preparation of trans-Crocetin with High Solubility, Stability, and Oral Bioavailability by Incorporation into Three Types of Cyclodextrins.

Crocetin (CRT), an active compound isolated from saffron, exhibits several pharmacological activities, including anti-tumor and immune-regulatory activities, and is effective against myocardial ischemia and coronary heart disease; however, its low stability and solubility limit its clinical application. Therefore, we investigated CRT inclusion complexes (ICs) with three cyclodextrins-α-CD, HP-ß-CD, and γ-CD-suitable for oral administration prepared using an ultrasonic method. Fourier transform infrared spectroscopy and powder X-ray diffraction indicated that the crystalline state of CRT in ICs disappeared, and intermolecular interactions were observed between CRT and CDs. 1H nuclear magnetic resonance and phase solubility studies confirmed CRT encapsulation in the CD cavity and the formation of ICs. In addition, we observed the morphology of ICs using scanning electron microscopy. All ICs showed a high drug encapsulation efficiency (approximately 90%) with 6500-10,000 times better solubilities than those of the pure drug. CRT showed rapid dissolution, whereas pure CRT was water-insoluble. The formation of ICs significantly improved the storage stability of CRT under heat, light, and moisture conditions. Further, the peak time of CRT in rats significantly decreased, and the relative bioavailability increased by approximately 3-4 times. In addition, the oral bioavailability of CRT IC was evaluated. Notably, the absorption rate and degree of the drug in rats were improved. This study illustrated the potential applications of CRT/CD ICs in the food, healthcare, and pharmaceutical industries, owing to their favorable dissolution, solubility, stability, and oral bioavailability.

Ternary Deep Eutectic Solvents System of Colchicine, 4-Hydroxyacetophenone, and Protocatechuic Acid and Characterization of Transdermal Enhancement Mechanism.

This study aimed to prepare colchicine (CO), 4-hydroxyacetophenone (HA), and protocatechuic acid (CA) contained in transdermal rubber plasters into a more releasable and acrylate pressure-sensitive adhesive (PSA) to optimize traditional Touguling rubber plasters (TOU) with enhanced transdermal permeability by using deep eutectic solvents (DES) technology. We compared the difference in the release behavior of CO between rubber plaster and PSA, determined the composition of the patch through pharmacodynamic experiments, explored the transdermal behavior of the three components, optimized the patch formula factors, and improved the penetration of CO through the skin. We also focused on elucidating the interactions among the three components of DES and the intricate relationship between DES and the skin. The melting point of DES was determined using DSC, while FTIR, 13C NMR, and ATR-FTIR were used to explore the intricate molecular mechanisms underlying the formation of DES, as well as its enhancement of skin permeability. The results of this investigation confirmed the successful formation of DES, marked by a discernible melting point at 27.33°C. The optimized patch, formulated with a molar ratio of 1:1:1 for CO, HA, and CA, significantly enhanced skin permeability, with the measured skin permeation quantities being 32.26 ± 2.98 µg/cm2, 117.67 ± 7.73 µg/cm2, and 56.79 ± 1.30 µg/cm2 respectively. Remarkably, the optimized patch also demonstrated similar analgesic and anti-inflammatory effects compared to commercial diclofenac diethylamide patches in different pharmacodynamics studies. The formation of DES altered drug compatibility with skin lipids and increased retention, driven by the interaction among the three component molecules through hydrogen bonding, effectively shielding the skin-binding sites and enhancing component permeation. In summary, the study demonstrated that optimized DES patches can concurrently enhance the penetration of CO, HA, and CA, thereby providing a promising approach for the development of DES in transdermal drug delivery systems. The findings also shed light on the molecular mechanisms underlying the transdermal behavior of DES and offer insights for developing more effective traditional Chinese medicine transdermal drug delivery systems.

The enantioselective enhancing effect and mechanistic insights of chiral enhancers in transdermal drug delivery.

Overlook of chiral consideration in transdermal drug delivery increases administrated dose and risk of side effects, decreasing therapeutical effects. To improve the transdermal delivery efficiency of eutomer, this work focused on investigating the law and mechanism of enantioselective enhancing effects of chiral permeation enhancers on drug enantiomers. Chiral nonsteroidal anti-inflammatory drugs and terpene permeation enhancers were selected as model drug and enhancers. The results indicated that the L-isomer of permeation enhancers increased the skin absorption of S-enantiomer of drug and D-isomer improve the permeation of R-enantiomer, in which the enhancement effect (ER) of L-menthol on S-enantiomer (ER = 3.23) was higher than that on R-enantiomer (ER = 1.49). According to the pharmacokinetics results, L-menthol tended to enhance the permeation of S-enantiomer better than R-enantiomer (2.56 fold), and showed excellent in vitro/in vivo correlations. The mechanism study showed that L-isomer of permeation enhancers improved the permeation of S-enantiomer by increasing the retention, but the D-isomer by improving partition for better permeation. Enantioselective mechanism indicated that the weaker chiral H-bond interaction between drug-chiral enhancers was caused by the enantiomeric conformation. Additionally, stronger chiral enhancers-skin interaction between L-isomer and S-conformation of ceramide produced better enhancing effects. In conclusion, enantioselective interaction of chiral drug-chiral enhancers and chiral enhancers-chiral skin played a critical role in transdermal drug delivery, rational utilization of which contributed to improving the uptake of eutomer and inhibiting distomers to decrease a half of dose and side effects, increasing transdermal therapeutical efficiency.

Sleep Architecture and Sleep EEG Alterations are Associated with Impaired Cognition Under Sleep Restriction.

Purpose: Many studies have investigated the cognitive, emotional, and other impairments caused by sleep restriction. However, few studies have explored the relationship between cognitive performance and changes in sleep structure and electroencephalography (EEG) during sleep. The present study aimed to examine whether changes in sleep structure and EEG can account for cognitive impairment caused by sleep restriction. Patients and Methods: Sixteen young adults spent five consecutive nights (adaptation 9h, baseline 8h, 1st restriction 6h, 2nd restriction 6h, and recovery 10h) in a sleep laboratory, with polysomnography recordings taken during sleep. Throughout waking periods in each condition, participants completed the psychomotor vigilance test (PVT), which measures vigilant attention, and the Go/No-Go task, which measures inhibition control. Results: The results showed that sleep restriction significantly decreased the proportion of N1 and N2 sleep, increased the proportion of N3 sleep, and reduced the time spent awake after sleep onset (WASO) and sleep onset latency. Poorer performance on the PVT and Go/No Go task was associated with longer WASO, a larger proportion of N3 sleep, and a smaller proportion of N2 sleep. Additionally, the power spectral density of delta waves significantly increased after sleep restriction, and this increase predicted a decrease in vigilance and inhibition control the next day. Conclusion: These findings suggest that sleep architecture and EEG signatures may partially explain cognitive impairment caused by sleep restriction.

Exosomes combined with biosynthesized cellulose conduits improve peripheral nerve regeneration.

Peripheral nerve injury is one of the more common forms of peripheral nerve disorders, and the most severe type of peripheral nerve injury is a defect with a gap. Biosynthetic cellulose membrane (BCM) is a commonly used material for repair and ligation of nerve defects with gaps. Meanwhile, exosomes from mesenchymal stem cells can promote cell growth and proliferation. We envision combining exosomes with BCMs to leverage the advantages of both to promote repair of peripheral nerve injury. Prepared exosomes were added to BCMs to form exosome-loaded BCMs (EXO-BCM) that were used for nerve repair in a rat model of sciatic nerve defects with gaps. We evaluated the repair activity using a pawprint experiment, measurement and statistical analyses of sciatica function index and thermal latency of paw withdrawal, and quantitation of the number and diameter of regenerated nerve fibers. Results indicated that EXO-BCM produced comprehensive and durable repair of peripheral nerve defects that were similar to those for autologous nerve transplantation, the gold standard for nerve defect repair. EXO-BCM is not predicted to cause donor site morbidity to the patient, in contrast to autologous nerve transplantation. Together these results indicate that an approach using EXO-BCM represents a promising alternative to autologous nerve transplantation, and could have broad applications for repair of nerve defects.

Enhanced amygdala-cingulate connectivity associates with better mood in both healthy and depressive individuals after sleep deprivation.

Sleep loss robustly disrupts mood and emotion regulation in healthy individuals but can have a transient antidepressant effect in a subset of patients with depression. The neural mechanisms underlying this paradoxical effect remain unclear. Previous studies suggest that the amygdala and dorsal nexus (DN) play key roles in depressive mood regulation. Here, we used functional MRI to examine associations between amygdala- and DN-related resting-state connectivity alterations and mood changes after one night of total sleep deprivation (TSD) in both healthy adults and patients with major depressive disorder using strictly controlled in-laboratory studies. Behavioral data showed that TSD increased negative mood in healthy participants but reduced depressive symptoms in 43% of patients. Imaging data showed that TSD enhanced both amygdala- and DN-related connectivity in healthy participants. Moreover, enhanced amygdala connectivity to the anterior cingulate cortex (ACC) after TSD associated with better mood in healthy participants and antidepressant effects in depressed patients. These findings support the key role of the amygdala-cingulate circuit in mood regulation in both healthy and depressed populations and suggest that rapid antidepressant treatment may target the enhancement of amygdala-ACC connectivity.

Glucose Dehydrogenases-Mediated Acclimation of an Important Rice Pest to Global Warming.

Global warming is posing a threat to animals. As a large group of widely distributed poikilothermal animals, insects are liable to heat stress. How insects deal with heat stress is worth highlighting. Acclimation may improve the heat tolerance of insects, but the underlying mechanism remains vague. In this study, the high temperature of 39 °C was used to select the third instar larvae of the rice leaf folder Cnaphalocrocis medinalis, an important insect pest of rice, for successive generations to establish the heat-acclimated strain (HA39). The molecular mechanism of heat acclimation was explored using this strain. The HA39 larvae showed stronger tolerance to 43 °C than the unacclimated strain (HA27) persistently reared at 27 °C. The HA39 larvae upregulated a glucose dehydrogenase gene, CmGMC10, to decrease the reactive oxygen species (ROS) level and increase the survival rate under heat stress. The HA39 larvae maintained a higher activity of antioxidases than the HA27 when confronted with an exogenous oxidant. Heat acclimation decreased the H2O2 level in larvae under heat stress which was associated with the upregulation of CmGMC10. The rice leaf folder larvae may acclimate to global warming via upregulating CmGMC10 to increase the activity of antioxidases and alleviate the oxidative damage of heat stress.

Construction of Imatinib Controlled Release Film-Forming System Based on Drug Ion-Pair and Oligomeric Ionic Liquids for the Long Local Therapy of Cutaneous Melanoma.

An imatinib controlled release film-forming system (FFS) was developed based on the drug ion-pair and newly designed oligomeric ionic liquids (OILs) for the topical therapy of cutaneous melanoma, which avoided the systemic side-effect of oral administration and maintained a long local therapy effect. The OILs significantly improved the drug release capacity about 1.5-fold, and the formability and stability of FFSs (verified by AFM/PLM). The in vivo anti-tumor efficacy studies in melanoma tumor bearing mice showed that compared with the oral capsules, the topical application of the optimized imatinib FFS significantly (p < 0.01) increased tumor inhibition rate (67.54 ± 2.72%) and the amount of apoptotic cells. As confirmed by FT-IR and NMR, the partial protonation of OILs were demonstrated to have high hydrogen bond forming capacity, thus showing low polarity and good biocompatibility. More importantly, based on 13C-NMR study, OILs demonstrated higher hydrogen bond forming capacity, and formed bridge between drug ion-pair (O-H of counter-ion) and PVA (O-H), increased the molecular mobility of PVA, thus maintaining a long drug release capacity. Therefore, an imatinib FFS was developed with good therapeutic effect and the effect of drug ion-pair and OILs on increasing the drug skin retention and controlled release of imatinib FFS for topical therapy was clarified at the molecular level, which provided a safe and effective way for the treatment of cutaneous melanoma.

A skin pharmacokinetics study of permeation enhancers: The root cause of dynamic enhancement effect on in vivo drug permeation.

Skin pharmacokinetics (SPK) of permeation enhancers can answer the question of why enhancement effects different at the kinetic level. Herein, SPK of permeation enhancers were classified into two categories, namely, lateral elimination (elimination to surrounding stratum corneum (SC)) and longitudinal elimination (elimination to deep epidermal (EP)). They were evaluated with a specific parameter for permeation enhancers, diffusion ratio (DRSC-EP), according to results of tissue-distribution test, molecular dynamic (MD) simulation, and confocal laser scanning microscopy (CLSM). The linear relationship between ke-enahcer and Δ Cmax-drug (R2 = 0.92), MRTenhancer and Δ Tmax-drug (R2 = 0.97), AUCt-enhancer and Δ AUCt-drug (R2 = 0.90) suggesting that SPK of permeation enhancers precisely controlled dynamic process of drug permeation in vivo. The molecular mechanisms of the dynamic effect of SPK process on drug transdermal behaviors were characterized by modulated-temperature differential scanning calorimetry (MTDSC), dielectric spectroscopy, small-angle X-ray scattering (SAXS), solid-state NMR. Permeation enhancers with high molecular weight (M.W.) and high polar surface area (P.S.A.) had good compatibility and strong interaction strength with SC, leading their lateral-elimination behavior, causing their low DRSC-EP and resulting in low ke-enhancer, long MRTenhancer, and large AUCt-enhancer. Consequently, skin barrier can be rapidly opened fast and to a great extent. In summary, compared with SPK of permeation enhancers with longitudinal elimination, SPK of permeation enhancers with lateral elimination can enable more sustainable and greater drug permeation. The information about SPK of permeation enhancers offered a criterion to estimate its permeation-enhancement effect on the drug and its subsequent application in transdermal formulations.

Controlled Interfacial Polymer Self-Assembly Coordinates Ultrahigh Drug Loading and Zero-Order Release in Particles Prepared under Continuous Flow.

Microparticles are successfully engineered through controlled interfacial self-assembly of polymers to harmonize ultrahigh drug loading with zero-order release of protein payloads. To address their poor miscibility with carrier materials, protein molecules are transformed into nanoparticles, whose surfaces are covered with polymer molecules. This polymer layer hinders the transfer of cargo nanoparticles from oil to water, achieving superior encapsulation efficiency (up to 99.9%). To control payload release, the polymer density at the oil-water interface is enhanced, forming a compact shell for microparticles. The resultant microparticles can harvest up to 49.9% mass fraction of proteins with zero-order release kinetics in vivo, enabling an efficient glycemic control in type 1 diabetes. Moreover, the precise control of engineering process offered through continuous flow results in high batch-to-batch reproducibility and, ultimately, excellent scale-up feasibility.

Donepezil accelerates the release of PLGA microparticles via catalyzing the polymer degradation regardless of the end groups and molecular weights.

Poly (lactic-co-glycolic acid) (PLGA) is one of the most successful polymers for sustained parenteral drug products in the market. However, rational selection of PLGA in the formulations is still challenging due to the lack of fundamental studies. The present study aimed to investigate the influence of donepezil (DP) on the in-vitro and in-vivo performance of PLGA sustained microspheres. Three kinds of PLGAs with different end groups and molecular weights were selected. Then DP-loaded PLGA microspheres (DP-MSs) with similar particle size, drug loading, and encapsulation efficiency were prepared using an o/w emulsion-solvent evaporation method. Laser diffraction and scanning electron microscopy showed that the prepared DP-MSs were about 35 µm and spherical in shape. Differential scanning calorimetry and X-ray diffraction indicated that DP was in an amorphous state inside the microspheres. Unexpectedly, the molecular weight and end group of PLGAs did not significantly influence the in-vitro and in-vivo performance of the DP-MSs. The gel permeation chromatography indicated that the degradation rates of PLGAs were accelerated with the incorporation of DP into the microspheres, and the molecular weight of all three kinds of PLGAs sharply dropped to about 11,000 Da within the initial three days. The basic catalysis effect induced by DP might be responsible for the accelerated degradation of PLGAs, which led to similar in-vitro release profiles of DP from different PLGA matrices. A point-to-point level A correlation between the in-vitro release and the in-vivo absorption was observed, which confirmed the accelerated release of DP from the DP-MSs in-vivo. The results indicated that the influence of DP on the degradation of PLGA should be considered when developing DP-sustained microspheres.

Persistent Ventral Anterior Cingulate Cortex and Resolved Amygdala Hyper-responses to Negative Outcomes After Depression Remission: A Combined Cross-sectional and Longitudinal Study.

BACKGROUND: Major depressive disorder (MDD) is a highly prevalent mood disorder affecting more than 300 million people worldwide. Biased processing of negative information and neural hyper-responses to negative events are hallmarks of depression. This study combined cross-sectional and longitudinal experiments to explore both persistent and resolved neural hyper-responses to negative outcomes from risky decision making in patients with current MDD (cMDD) and remitted MDD (rMDD). METHODS: A total of 264 subjects participated in the cross-sectional study, including 117 patients with medication-naïve, first-episode current depression; 45 patients with rMDD with only 1 episode of depression; and 102 healthy control subjects. Participants completed a modified balloon analog risk task during functional magnetic resonance imaging. In the longitudinal arm of the study, 42 patients with cMDD were followed and 26 patients with rMDD were studied again after 8 weeks of antidepressant treatment. RESULTS: Patients with cMDD showed hyper-responses to loss outcomes in multiple limbic regions including the amygdala and ventral anterior cingulate cortex (vACC). Amygdala but not vACC hyperactivity correlated with depression scores in patients with cMDD. Furthermore, amygdala hyperactivity resolved while vACC hyperactivity persisted in patients with rMDD in both cross-sectional and longitudinal studies. CONCLUSIONS: These findings provide consistent evidence supporting differential patterns of amygdala and vACC hyper-responses to negative outcomes during depression remission. Amygdala hyperactivity may be a symptomatic and state-dependent marker of depressive neural responses, while vACC hyperactivity may reflect a persistent and state-independent effect of depression on brain function. These findings offer new insights into the neural underpinnings of depression remission and prevention of depression recurrence.

High drug-loading and controlled-release hydroxyphenyl-polyacrylate adhesive for transdermal patch.

Long-acting transdermal drug delivery system (TDDS) requires high drug-loading and drug controlled-release. To simultaneously improve drug-polymer miscibility and realize drug controlled-release, this work aimed to develop a new pressure sensitive adhesive modified with hydroxyphenyl (HP-PSA) by introducing doubly ionic H-bond into drug-PSA interaction. Eight model drugs divided into R3N, R2NH and no N type were chosen to understand the characteristics of the HP-PSA and inner mechanism. The results showed that the doubly ionic H-bond between R3N and R2NH type drugs and HP-PSA, differing from the ionic bond and neutral H-bond, was a reversible and relatively strong interaction. It could significantly enhance their drug-loading by 1.5 to 7 times and control drug release rate to its 1/5 to 1/2 without altering its total release properties, outperforming the commercial Duro-Tak® 87-2510 and Duro-Tak® 87-2852 adhesives. According to the pharmacokinetics results, the high drug-loading patches based on HP-PSA achieved a sustainable plasma drug concentration avoiding burst release, and over 2 times area under concentration-time curve (AUC) as well as 6 times mean residence time (MRT) revealed its potential to realize long-acting drug delivery. Additionally, its safety and mechanical features were satisfied. The mechanism study showed that the repulsion of the ionic drugs in HP-PSA increased drug-loading, and the relatively strong interaction could also control drug release. The incomplete H-bond transfer determined its reversibility, thus making the drug release percentage up to that of non-functional PSA. In conclusion, the high drug-loading efficiency and drug controlled-release capacity of HP-PSA, as well as its unique interaction, would contribute to the development of TDDS. Moreover, the construction of the doubly ionic H-bond would provide further inspiration for various drug delivery systems in the non-polar environment.

The role of hydrophilic/hydrophobic group ratio of polyvinyl alcohol on the miscibility of amlodipine in orodispersible films: From molecular mechanism study to product attributes.

The miscibility of the therapeutic drug in the polymer matrix is the key to the successful design and development of orodispersible films (ODFs). In the present study, four hydrolyzed polyvinyl alcohols (PVAs) with identical polymerization degree were investigated as carriers for Amlodipine (AML) ODFs systematically. The drug-polymer miscibility and the intermolecular interaction were investigated by Flory-Huggins theory, Gordon-Taylor theory, molecular simulation, FTIR, Raman and 1H NMR. The product attributes of ODFs were also studied. A pharmacokinetic study in rats was then conducted using the film product of PVA5-72, the best performer tested. The results revealed that the drug-polymer miscibility decreased linearly with the increase of hydrolyzed degree of PVA. Hydrogen bonds formed between the drug and the hydrophilic and hydrophobic groups of PVAs were the main intermolecular interaction that caused the differences in drug-polymer miscibility. Furthermore, drug-polymer interaction influenced the product attributes of ODFs, including dissolution profile, mechanical properties and physical stability. The pharmacokinetic study showed the ODFs disintegrated rapidly, and the amorphous AML dissolved and absorbed in the gastrointestinal tract, which was comparable to the commercial product. The research offered a foundation for development scientists in designing and formulating PVA films.

2023 China Guidelines for Lipid Management / 老年心脏病学杂志（英文版）

Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of death among urban and rural residents in China, and elevated low-density lipoprotein cholesterol (LDL-C) is a risk factor for ASCVD. Considering the increasing burden of ASCVD, lipid management is of the utmost importance. In recent years, research on blood lipids has made breakthroughs around the world, hence a revision of China guidelines for lipid management is imperative, especially since the target lipid levels in the general population vary in respect to the risk of ASCVD. The level of LDL-C, which can be regarded as appropriate in a population without frisk factors, can be considered abnormal in people at high risk of developing ASCVD. As a result, the "Guidelines for the prevention and treatment of dyslipidemia" were adapted into the "China Guidelines for Lipid Management" (henceforth referred to as the new guidelines) by an Experts' committee after careful deliberation. The new guidelines still recommend LDL-C as the primary target for lipid control, with CVD risk stratification to determine its target value. These guidelines recommend that moderate intensity statin therapy in adjunct with a heart-healthy lifestyle, be used as an initial line of treatment, followed by cholesterol absorption inhibitors or/and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, as necessary. The new guidelines provide guidance for lipid management across various age groups, from children to the elderly. The aim of these guidelines is to comprehensively improve the management of lipids and promote the prevention and treatment of ASCVD by guiding clinical practice.

Sleep-improving mechanisms of Jiu Wei Bu Xue Oral Liquid on regulating Glu/GABA balance in insomnia rats based on network pharmacology and experimental verification / 药学学报

This study aimed to investigate the mechanism of Jiu Wei Bu Xue Oral Liquid on insomnia rats combining the methods of network pharmacology, molecular docking and experimental verification. UPLC-Q-TOF-MS/MS method and TCMIP, TCMSP databases were used to collect the ingredients and targets of Jiu Wei Bu Xue Oral Liquid. Protein-protein interactions and network analysis were performed to screen the key network targets and putative active ingredients of Jiu Wei Bu Xue Oral Liquid in treatment of insomnia, and then following by biological function and KEGG pathway analysis. Then binding ability for key network targets and putative active ingredients were predicted with molecular docking. The prediction targets were validated in para-chlorophenylalanine (PCPA) induced insomnia rats with administration of Jiu Wei Bu Xue Oral Liquid (2, 4, 8 mL·kg-1) for 7 days. Pentobarbital sodium induced sleeping test were performed to evaluate the synergistic sleep-aiding effect of Jiu Wei Bu Xue Oral Liquid. Then glutamic acid (Glu), γ-aminobutyrate (GABA) content and glutamate decarboxylase 1 (GAD67) activity in hypothalamus or hippocampus were evaluated, and the expressions of GAD67, γ-aminobutyric acid receptor subunit α1 (GABRA1) and γ-aminobutyric acid receptor subunit β2 (GABRB2) in hippocampus were detected by qRT-PCR and Western blot methods. Animal experiments were approved by the Institutional Committee on Animal Care of Guangxi Institute of Chinese Medicine & Pharmaceutical Science (the number of permission: 2022060802). Results showed that 16 key network targets and 16 putative active ingredients were obtained by analyzing the herbs-ingredients-targets network of Jiu Wei Bu Xue Oral Liquid in treatment of insomnia. Network pharmacology and molecular docking all indicated these active ingredients, for example atractylenolide Ⅲ, showed better binding ability with GABRA1 and GABRB2. Animal study indicated that, compared to PCPA-induced insomnia model, Jiu Wei Bu Xue Oral Liquid remarkably shortened the sleeping latency and increased the sleeping duration, increased GAD67 activity and the production of GABA in hippocampus of insomnia rats, as well as the expressions of GAD67, GABRA1 and GABRB2, while decreased Glu content in hypothalamus, leading to decreasing of Glu/GABA ratio and recovery of Glu-GABA balance. These results indicated that Jiu Wei Bu Xue Oral Liquid improved insomnia symptoms and helped maintain the Glu-GABA balance within hypothalamus and hippocampus, and reduced the excitatory neurotoxicity within brain. The mechanism may due to the elevation of GAD67 expression and enzyme activity, and the enhancement of type-A GABA receptor (GABAAR)-mediated neurons inhibition.