Risk of major depressive increases with increasing frequency of alcohol drinking: a bidirectional two-sample Mendelian randomization analysis.

Introduction: A growing body of evidence suggests that alcohol use disorders coexist with depression. However, the causal relationship between alcohol consumption and depression remains a topic of controversy. Methods: We conducted a two-sample two-way Mendelian randomization analysis using genetic variants associated with alcohol use and major depressive disorder from a genome-wide association study. Results: Our research indicates that drinking alcohol can reduce the risk of major depression (odds ratio: 0.71, 95% confidence interval: 0.54~0.93, p = 0.01), while increasing the frequency of drinking can increase the risk of major depression (odds ratio: 1.09, 95% confidence interval: 1.00~1.18, p = 0.04). Furthermore, our multivariate MR analysis demonstrated that even after accounting for different types of drinking, the promoting effect of drinking frequency on the likelihood of developing major depression still persists (odds ratio: 1.13, 95% confidence interval: 1.04~1.23, p = 0.005). Additionally, mediation analysis using a two-step MR approach revealed that this effect is partially mediated by the adiposity index, with a mediated proportion of 37.5% (95% confidence interval: 0.22 to 0.38). Discussion: In this study, we found that alcohol consumption can alleviate major depression, while alcohol intake frequency can aggravate it.These findings have important implications for the development of prevention and intervention strategies targeting alcohol-related depression.

Effect of ion pair strategy on transdermal delivery of guanfacine: Which factor dominates drug permeation?

Ion pair is an effective chemical approach to promoting drug transdermal permeation, and the traditional interpretation for its enhanced permeation effect is mainly attributed to counterions altering the physicochemical properties of the drug (lipophilicity, melting point, etc.). In this work, guanfacine (GFC), a non-stimulant for anti-attention deficit and hyperactivity disorder (ADHD), was used as a model drug, and several organic or inorganic acids were designed thereby successfully constructing ion pairs. The transdermal permeation ability of ion pairs through isolated porcine skin was observed and ranked as follows: guanfacine caprylate (GFC-CA) > GFC > guanfacine laurate (GFC-LA) > guanfacine fumarate (GFC-FA) > guanfacine hydrochloride (GFC-HA) > guanfacine palmitate (GFC-PA). The effect of key physicochemical properties (octanol-water partition coefficient, molecular volume, melting point) on the transdermal permeation rate of the model drug was analyzed in detail. In addition, GFC-CA was observed to alter the lipid structure of the skin, suggesting the traditional explanation of the action of ion pair may be inadequate and underrated, and ion pair may also enhance permeation by disrupting skin structure. The intriguing phenomenon is expected to provide a novel approach to achieving precise transdermal drug delivery.

Bacterial Drug Delivery Systems for Cancer Therapy: "Why" and "How".

Cancer is one of the major diseases that endanger human health. However, the use of anticancer drugs is accompanied by a series of side effects. Suitable drug delivery systems can reduce the toxic side effects of drugs and enhance the bioavailability of drugs, among which targeted drug delivery systems are the main development direction of anticancer drug delivery systems. Bacteria is a novel drug delivery system that has shown great potential in cancer therapy because of its tumor-targeting, oncolytic, and immunomodulatory properties. In this review, we systematically describe the reasons why bacteria are suitable carriers of anticancer drugs and the mechanisms by which these advantages arise. Secondly, we outline strategies on how to load drugs onto bacterial carriers. These drug-loading strategies include surface modification and internal modification of bacteria. We focus on the drug-loading strategy because appropriate strategies play a key role in ensuring the stability of the delivery system and improving drug efficacy. Lastly, we also describe the current state of bacterial clinical trials and discuss current challenges. This review summarizes the advantages and various drug-loading strategies of bacteria for cancer therapy and will contribute to the development of bacterial drug delivery systems.

Design and evaluation of gastro-swelling/gastro-floating sustained-release tablets of brivaracetam for epilepsy therapy.

To prolong the absorption of the drug and achieve the effect of gastric retention, new brivaracetam tablets together with the characteristics of rapid swelling and sustained floating have been developed here. The tablets were optimized and prepared by direct compression techniques using Kollidon® SR and cross-linked polyvinylpyrrolidone (PVPP) XL as the matrix and disintegrant respectively, and carbomer 71G NF and polyethylene oxide (PEO) N60K as the gel materials to achieve sustained release effect. The characteristics of static expansion, floating time, drug release and dynamic swelling performance in vitro of the tablets were evaluated. The optimized formulations (F5 and F10) exhibited satisfactory swelling and floating properties, mechanical strength, and in vitro sustained-release characteristic with diffusion and matrix erosion mechanisms. X-ray images of beagle dogs showed that the tablet F5 could be retained in the stomach for more than 6 h. Furthermore, the pharmacokinetic studies in volunteers exhibited that the bioavailability of F5 and F10 was 95.70% (90% CI, 83.80%-109.28%) and 103.39% (90% CI, 87.61%-122.01%), respectively, relative to commercial tablets, with Tmax prolonged, demonstrating an excellent sustained-release effect. Therefore, the present system can reduce dosing frequency and improve patient compliance, which is expected to be a promising treatment option for epilepsy patients.

Emergency shelter allocation planning technology for large-scale evacuation based on quantum genetic algorithm.

Introduction: Shelter allocation is one of the most important measures in urban disaster prevention and mitigation planning. Meanwhile, it is essentially a comprehensive planning problem combining resource allocation and traffic routing. A reasonable allocation scheme can avoid congestion, improve evacuation efficiency, and reduce the casualty rate. Owing to the large region and large evacuation population demand, quickly solving the complex allocation problem is somewhat challenging, and thus, the optimal results are difficult to obtain with the increase of evacuation scale by traditional allocation methods. Methods: This article aims to establish a shelter allocation model for large-scale evacuation, which employs an improved quantum genetic algorithm (IQGA) based on spreading operation and considering the total evacuation distance, the capacity constraint of evacuation sites, and the dispersion of allocation results, and compare allocation schemes of the spreading model with those of models that consider different constraints. Results and discussion: Results show that the allocation model with the spreading operation has better allocation results than that without the spreading operation. For the allocation model with spreading operation, the spreading model with different spreading speeds is more reasonable than that with the same spreading speed, and the allocation results are closer to the ideal results with the increase of constraints. In addition, according to the allocation results, the evacuation route map and the evacuation heat map are drawn to intuitively understand the distribution scheme of each shelter.

Detection of Active Sacroiliitis with Ankylosing Spondylitis through Intravoxel Incoherent Motion Diffusion-Weighted MR Imaging.

OBJECTIVE: To confirm feasibility and assess intravoxel incoherent motion (IVIM) to differentiate active sacroiliitis and ankylosing spondylitis.. METHODS: Forty-one patients were divided into two groups, an active group (n = 20) and a chronic group (n = 21), according to the Bath Ankylosing Spondylitis (AS) Disease Activity Index (BASDAI) and laboratory parameters. In addition, 21 healthy volunteers were chosen as the control group. Tissue diffusivity (Dslow), perfusion fraction (f), and pseudo-diffusion coefficient (Dfast) values were obtained for all three groups. One-way analysis of variance and receiver operating characteristic analysis were performed for all parameters. RESULTS: There was good interobserver agreement on the measurements between the two observers. The optimal cut-off values (with respective AUC, sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio) between active and chronic groups were Dslow = 0.53 × 10(-3) mm(2)/s (0.976, 90%, 95.2%, 18.9, 0.10) and f = 0.09 (0.545, 20%, 95.5%, 4.2, 0.84), and between chronic and control groups were Dslow = 0.22 × 10(-3) mm(2)/s (0.517, 9.52%, 100%, no number, 0.9) and f = 0.09 (0.935, 95.24%, 80.95%, 5, 0.059). CONCLUSION: Dslow and f of IVIM diffusion-weighted (DW)-MRI in AS show a significant difference in the values of diffusion of water molecules and fractional perfusion-related volume among the three groups. KEY POINTS: • D slow can be used to differentiate the activity of AS. • With perfusion fraction, the sensitivity of differentiating the AS activity is improved. • IVIM DWI plays an important role in detecting the activity in patients with AS.