China Initiative for Multi-Domain Intervention (CHINA-IN-MUDI) to Prevent Cognitive Decline: Study Design and Progress.

BACKGROUND: Alzheimer's disease (AD), the most common type of irreversible dementia, is predicted to affect 152 million people by 2050. Evidence from large-scale preventive randomized controlled trials (RCTs) on modifiable risk variables in Europe has shown that multi-domain lifestyle treatments for older persons at high risk of dementia may be practical and effective. Given the substantial differences between the Chinese and European populations in terms of demographics and living conditions, direct adoption of the European program in China remains unfeasible. Although a RCT has been conducted in China previously, its participants were mainly from rural areas in northern China and, thus, are not representative of the entire nation.There is an urgent need to establish cohorts that represent different economic, cultural, and geographical situations in order to explore implementation strategies and evaluate the effects of early multi-domain interventions more comprehensively and accurately. MEDTODS: We developed an integrated intervention procedure implemented in urban neighborhood settings, namely China Initiative for Multi-Domain Intervention (CHINA-IN-MUDI). CHINA-IN-MUDI is a 2-year multicenter open-label cluster-randomised controlled trial centered around a Chinese-style multi-domain intervention to prevent cognitive decline. Participants aged 60-80 years were recruited from a nationally representative study, i.e. China Healthy Aging and Dementia Study cohort. An external harmonization process was carried out to preserve the original FINGER design. Subsequently, we standardized a series of Chinese-style intervention programs to align with cultural and socioeconomic status. Additionally, we expanded the secondary outcome list to include genomic and proteomic analyses. To enhance adherence and facilitate implementation, we leveraged an e-health application. RESULTS: Screening commenced in July 2022. Currently, 1,965 participants have been randomized into lifestyle intervention (n = 772) and control groups (n = 1,193). Both the intervention and control groups exhibited similar baseline characteristics. Several lifestyle and vascular risk factors were present, indicating a potential window of opportunity for intervention. The intervention will be completed by 2025. CONCLUSIONS: This project will contribute to the evaluation of the effectiveness and safety of intervention strategies in controlling AD risk and reducing clinical events, providing a basis for public health decision-making in China.

Germanene on single-layer ZnSe substrate: novel electronic and optical properties.

In this work, the structural, electronic and optical properties of germanene and ZnSe substrate nanocomposites have been investigated using first-principles calculations. We found that the large direct-gap ZnSe semiconductors and zero-gap germanene form a typical orbital hybridization heterostructure with a strong binding energy, which shows a moderate direct band gap of 0.503 eV in the most stable pattern. Furthermore, the heterostructure undergoes semiconductor-to-metal band gap transition when subjected to external out-of-plane electric field. We also found that applying external strain and compressing the interlayer distance are two simple ways of tuning the electronic structure. An unexpected indirect-direct band gap transition is also observed in the AAII pattern via adjusting the interlayer distance. Quite interestingly, the calculated results exhibit that the germanene/ZnSe heterobilayer structure has perfect optical absorption in the solar spectrum as well as the infrared and UV light zones, which is superior to that of the individual ZnSe substrate and germanene. The staggered interfacial gap and tunability of the energy band structure via interlayer distance and external electric field and strain thus make the germanene/ZnSe heterostructure a promising candidate for field effect transistors (FETs) and nanoelectronic applications.

The correlation analysis of human embryonic MMP-9 secretion and embryo quality.

OBJECTIVE: The correlation of the embryo matrix metalloproteinase-9 (MMP-9) secretion, embryonic development and clinical pregnancy was investigated. MATERIALS AND METHODS: The embryo culture from in vitro fertilization-embryo transfer (IVF-ET) patients were collected in the Xuzhou Central Hospital from January 2013 to September 2014. At the same time, the embryo grade was recorded. The secretion of the MMP-9 in the embryo culture was detected through hybridization (Dot-blot) and enzyme-linked immunosorbent assay (ELISA). The clinical pregnancy outcome was followed after one month of the embryo transfer. RESULTS: With the embryonic development from 2-cell to 8-cell, embryonic MMP-9 secretion increased gradually (p < 0.05). Though 8/I embryo, the secretion of MMP-9 are not identical. The quantitative detection of the MMP-9 secretion of the 8-cell embryo by ELISA is higher as is the embryo score, but the low secretion of embryo score is lower (p < 0.001). As 8/I embryos, the clinical pregnancy rate (77.3%) of the MMP-9 high secretion embryos is higher than the low secretion embryos (16.7%) (p < 0.001). CONCLUSIONS: The secretion of the embryonic MMP-9 is closely related to the quality of the embryo and embryo implantation. It is speculated that MMP-9 may become one of the criteria to evaluate the quality of the embryos.

Estimation of number of subjects required for comparison of drug versus control in adaptive designs.

INTRODUCTION: Adaptive designs have often been proposed as a way of using accruing data to affect future allocation scheme in clinical trials. The goal is to assign more patients to the better treatment. To implement clinical trials efficiently, sample size must be estimated in advance. In adaptive design, it is difficult to calculate the required sample size, because the allocation probabilities keep changing during the course of the trials. METHODS: We focus on the sample size of two-arm (drug versus control) clinical trials. Based on its asymptotic properties, a formula of calculating sample size is derived for the randomised play-the-winner rule. We also compare sample size and power between the randomised play-the-winner rule and equal allocation. Some simulation studies illustrate the operating characteristics of the designs. RESULTS AND DISCUSSION: The required sample size of the randomised play-the-winner rule is slightly larger than that of the equal allocation design in most cases. The randomised play-the-winner rule is recommended for ethical reasons.