Circulating cytokines and vascular dementia: A bi-directional Mendelian randomization study.

Inflammatory responses are associated with the development of vascular dementia (VaD). Circulating cytokines modulate the inflammatory response and are important for the immune system. To further elucidate the role of the immune system in VaD, we used Mendelian randomization (MR) to comprehensively and bi-directionally assess the role of circulating cytokines in VaD. Using state-of-the-art genome-wide association studies, we primarily assessed whether different genetic levels of 41 circulating cytokines affect the risk of developing VaD and, in turn, whether the genetic risk of VaD affects these circulating cytokines. We used inverse variance weighting (IVW) and several other MR methods to assess the bidirectional causality between circulating cytokines and VaD, and performed sensitivity analyses. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) was inversely associated with VaD risk [odds ratio (OR): 0.74, 95 % confidence interval (CI): 0.60-0.92, P = 0.007, 0.007]. VaD was associated with seven circulating cytokines: macrophage inflammatory protein 1b (MIP-1 beta) [OR: 1.05, 95 % CI: 1.01-1.08, P = 0.009], Interleukin-12p70 (IL-12) [OR: 1.04, 95 % CI: 1.00-1.08, P = 0.047], Interleukin-17 (IL-17) [OR: 1.04, 95 % CI: 1.00-1.07, P = 0.038], Interleukin-7 (IL-7) [OR: 1.07, 95 % CI: 1.02-1.12, P = 0.009], Interferon gamma (IFN-γ) [OR: 1.03, 95 % CI: 1.00-1.07, P = 0.046], Granulocyte-colony stimulating factor (GCSF) [OR: 1.06, 95 % CI: 1.02-1.09, P = 0.001], Fibroblast growth factor (FGF) [P = 0.001], and Fibroblast growth factor (FGF) [P = 0.001]. Fibroblast growth factor basic (FGF-Basic) [OR: 1.04, 95 % CI: 1.01-1.08, P = 0.02] were positively correlated. Circulating cytokines are associated with VaD, and further studies are needed to determine whether they are effective targets for intervention to prevent or treat VaD.

Transition in metabolic health phenotypes across general adiposity categories and association with the risk of depression: a prospective analysis.

BACKGROUND: The association between obesity and depression may partly depend on the contextual metabolic health. The effect of change in metabolic health status over time on subsequent depression risk remains unclear. We aimed to assess the prospective association between metabolic health and its change over time and the risk of depression across body mass index (BMI) categories. METHODS: Based on a nationally representative cohort, we included participants enrolled at the wave 2 (2004-2005) of the English Longitudinal Study of Ageing and with follow-up for depression at wave 8 (2016-2017). Participants were cross-classified by BMI categories and metabolic health (defined by the absence of hypertension, diabetes, and hypercholesterolemia) at baseline or its change over time (during waves 3-6). Logistic regression model was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for the risk of depression at follow-up stratified by BMI category and metabolic health status with adjustment for potential confounders. RESULTS: The risk of depression was increased for participants with metabolically healthy obesity compared with healthy nonobese participants, and the risk was highest for those with metabolically unhealthy obesity (OR 1.62, 95% CI 1.18-2.20). Particularly hypertension and diabetes contribute most to the increased risk. The majority of metabolically healthy participants converted to unhealthy metabolic phenotype (50.1% of those with obesity over 8 years), which was associated with an increased risk of depression. Participants who maintained metabolically healthy obesity were still at higher risk (1.99, 1.33-2.72), with the highest risk observed for those with stable unhealthy metabolic phenotypes. CONCLUSIONS: Obesity remains a risk factor for depression, independent of whether other metabolic risk factors are present or whether participants convert to unhealthy metabolic phenotypes over time. Long-term maintenance of metabolic health and healthy body weight may be beneficial for the population mental well-being.

Metabolic-dysfunction associated steatotic liver disease-related diseases, cognition and dementia: A two-sample mendelian randomization study.

BACKGROUND: The results of current studies on metabolic-dysfunction associated steatotic liver disease (MASLD)-related diseases, cognition and dementia are inconsistent. This study aimed to elucidate the effects of MASLD-related diseases on cognition and dementia. METHODS: By using single-nucleotide polymorphisms (SNPs) associated with different traits of NAFLD (chronically elevated serum alanine aminotransferase levels [cALT], imaging-accessed and biopsy-proven NAFLD), metabolic dysfunction-associated steatohepatitis, and liver fibrosis and cirrhosis, we employed three methods of mendelian randomization (MR) analysis (inverse-variance weighted [IVW], weighted median, and MR-Egger) to determine the causal relationships between MASLD-related diseases and cognition and dementia. We used Cochran's Q test to examine the heterogeneity, and MR-PRESSO was used to identify outliers (NbDistribution = 10000). The horizontal pleiotropy was evaluated using the MR-Egger intercept test. A leave-one-out analysis was used to assess the impact of individual SNP on the overall MR results. We also repeated the MR analysis after excluding SNPs associated with confounding factors. RESULTS: The results of MR analysis suggested positive causal associations between MASLD confirmed by liver biopsy (p of IVW = 0.020, OR = 1.660, 95%CI = 1.082-2.546) and liver fibrosis and cirrhosis (p of IVW = 0.009, OR = 1.849, 95%CI = 1.169-2.922) with vascular dementia (VD). However, there was no evidence of a causal link between MASLD-related diseases and cognitive performance and other types of dementia (any dementia, Alzheimer's disease, dementia with lewy bodies, and frontotemporal dementia). Sensitivity tests supported the robustness of the results. CONCLUSIONS: This two-sample MR analysis suggests that genetically predicted MASLD and liver fibrosis and cirrhosis may increase the VD risk. Nonetheless, the causal effects of NAFLD-related diseases on VD need more in-depth research.

Treatment of diabetic foot ulcers with external application of Chinese herbal medicine: An overview of overlapping systematic reviews.

This overview of systematic reviews (SRs) and meta-analysis (MAs) aimed to systematically collate, appraise and synthesize evidence for the treatment of diabetic foot ulcers (DFUs) with the external application of Chinese herbal medicine (CHM). SRs/MAs of external application of CHM for DFUs were collected by searching Cochrane Library, Web of science, CNKI, PubMed, VIP, Embase and Wanfang. Two independent reviewers carried out the literature selection and data extraction. Subsequently, AMSTAR-2 tool, PRISMA, and GRADE system were applied by two reviewers independently to evaluate the methodological quality, reporting quality, and evidence quality of the included studies, respectively. Eight SRs/MAs met the eligibility criteria and were included. According to AMSTAR-2, a very low methodological quality assessment was given to the included SRs/MAs due to the flaws of items 2, 4 and 7. The PRISMA system identified protocol and registration weaknesses, as well as search method weaknesses. With GRADE, no high-quality evidence was identified to support the role of external application of CHM for DFUs, and the quality of evidence for the vast majority of outcomes was rated as low or moderate. In conclusion, low- to moderate-quality evidence supports the promise of external application of CHM for the treatment of DFUs. Due to the limitations of the evidence supporting external application of CHM for DFUs, rigorously designed and larger samples of high-quality studies are needed going forward before broad recommendations can be made.

Moxibustion Treatment of COVID-19 and Rehabilitation Period of COVID-19: A Scoping Review.

Objective: The aim of this study is to provide a scoping review of the clinical literature on moxibustion therapy for the treatment of Coronavirus disease 2019 (COVID-19). Design: The PubMed, Embase, Cochrane Library, MEDLINE, CNKI, Wanfang, and VIP databases were searched from January 1, 2020, to August 31, 2022. Essential data were extracted from each article, and the data were displayed using tables and graphs. The study did not require IRB approval. Results: This scoping review included 14 research articles: 8 observational studies, 5 randomized controlled trials, and 1 nonrandomized clinical trial. All the studies were published by Chinese scholars. The findings revealed that moxibustion can contribute to reducing the symptoms of patients with COVID-19, improving inflammation and immune indicators, and shortening the time of nucleic acid negative conversion. Moxibustion confers curative effects on patients of all ages and degrees of illness. In addition, moxibustion can optimize the prognosis of patients in the rehabilitation period. The most commonly chosen acupoints are ST36, RN4, RN8, and RN12. No side effect was mentioned in the included studies. Conclusion: Moxibustion can produce a good effect in the treatment and rehabilitation of patients with COVID-19. It is safe, effective, simple, and noninvasive and should be included as standard care.