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.

[Expression of CD10 in cancer-associated fibroblasts and its effect on initiation and progression of colorectal carcinoma].

Objective: To study CD10 expression in cancer-associated fibroblasts (CAF) and related effect on colorectal cancer initiation and progression. Methods: A total of 226 surgical removed colorectal cancer specimens were collected with patient follow-up data. A panel of immunohistochemical markers(CD10, Ki-67, p53, cyclin D1 and ß-catenin) were evaluated in carcinomas, adjacent adenomas and paired normal colorectal mucosa with correlation of clinicopathological parameters. Results: CD10 expression was not detected in the normal colorectal mucosa by immunohistochemistry. The percentages of CD10 expression in CAF were 80.1% (181/226) in carcinoma tissue and 58.4% (132/226) in adjacent adenomas, respectively. SMA was positive and desmin was negative. The proliferation index of Ki-67 was 84.1%(190/226) in tumor tissue, 63.7%(144/226)in adenoma zone, and 7.1% (16/226) in the normal mucosa. The rate of p53 mutation was 50.4% (114/226)in tumor tissue, 53.1%(120/226)in adenoma and 8.8%(20/226)in the normal mucosa. The expression rate of cyclin D1 was 83.6%(189/226) in tumor tissue, 48.7%(110/226)in adenoma zone, but negative in the normal mucosa. For normal tissue, the percentages of ß-catenin expression was 53.1%(120/226), 95.6%(216/226) and 10.6%(24/226) in the cell membrane, cytoplasm and nucleus, respectively.The ß-catenin expression in cell membrane, cytoplasm and nucleus was 17.7%(40/226), 100.0% (226/226) and 49.1% (111/226), respectively, in the tumor cells. The expression of Ki-67, p53, cyclin D1 and ß-catenin in the tumor cells was positively associated with CD10 in CAF (P<0.05). The CD10 expression was different in patients with different gender, age and differentiation degree (P<0.05), whereas the depth of invasion, lymph node metastasis and tumor emboli did not relate to it. Overall survival rates in CD10 negative group were higher than that in CD10 positive group. Conclusions: CD10 is only expressed in CAF. Significant correlation is found between CAF with high CD10 expression and neighboring tumor cells with p53, Ki-67 and cyclin D1 expression and nuclear ß-catenin expression. CD10-positive CAF and p53, ß-catenin, cyclin D1 and Ki-67-labelled colorectal cancer cells together with nuclear ß-catenin expression may provide helps for diagnosis of colorectal carcinoma from an angle of tumor interstitial microenvironment. CAF with CD10 expression may promote the initiation and progression of colon cancer cells by activating Wnt signaling pathway.