ObjectiveTo analyze the research hotspot and future trend of non-invasive brain stimulation (NIBS) in Alzheimer's disease. MethodsRelevant literature on application of NIBS in Alzheimer's disease from January, 2014 to October, 2024 was retrieved from the Web of Science Core Collection database. CiteSpace 6.4.R1 was used to perform a bibliometric analysis and to create knowledge maps, including annual publication volume, countries, institutions, authors, keywords and co-cited references. ResultsA total of 731 articles were included, showing an increasing trend in annual publication volume. The United States was the leading country in publication volume, Harvard University was the most productive institution, and Giacomo Koch was the most prolific author. Brain Stimulation was the most frequently cited journal. Highly focused keywords included cognitive impairment, memory, dementia, transcranial magnetic stimulation and transcranial direct current stimulation. Bursting keywords in the past two years included transcranial alternating current stimulation, functional magnetic resonance imaging, brain-derived neurotrophic factor and oxidative stress. ConclusionResearch interest in NIBS within the field of Alzheimer's disease has been steadily increasing. The research hotspots include the effect and mechanism of NIBS on cognitive function and the impact of stimulating different brain regions on cognitive outcome. Future research may focus on integrating NIBS with techniques such as functional magnetic resonance imaging to achieve individualized and precise stimulation.

The development of bone in human body and the maintenance of bone mass in adulthood are regulated by a variety of biological factors. Myocyte enhancer factor 2C (MEF2C), as one of the many factors regulating bone tissue development and balance, has been shown to play a key role in bone development and metabolism. However, there is limited systematic analysis on the effects of MEF2C on bone tissue. This article reviews the role of MEF2C in bone development and metabolism. During bone development, MEF2C promotes the development of neural crest cells (NC) into craniofacial cartilage and directly promotes cartilage hypertrophy. In terms of bone metabolism, MEF2C exhibits a differentiated regulatory model across different types of osteocytes, demonstrating both promoting and other potential regulatory effects on bone formation, with its stimulating effect on osteoclasts being determined. In view of the complex roles of MEF2C in bone tissue, this paper also discusses its effects on some bone diseases, providing valuable insights for the physiological study of bone tissue and strategies for the prevention of bone diseases.
Humans ; MEF2 Transcription Factors/physiology* ; Bone and Bones/metabolism* ; Animals ; Bone Development/physiology* ; Osteogenesis/physiology* ; Myogenic Regulatory Factors/physiology*

Medical institutions, with their clinical practice foundation and abundant human use experience data, have become important carriers for the inheritance and innovation of traditional Chinese medicine(TCM) and the "cradles" of the preparation of new TCM. To effectively promote the transformation of new TCM originating from the TCM clinical practice in medical institutions and establish an effective evaluation index system for the transformation of new TCM conforming to the characteristics of TCM, consensus experts adopted the literature research, questionnaire survey, Delphi method, etc. By focusing on the policy and technical evaluation of new TCM originating from the TCM clinical practice in medical institutions, a comprehensive evaluation from the dimensions of drug safety, efficacy, feasibility, and characteristic advantages was conducted, thus forming a comprehensive evaluation system with four primary indicators and 37 secondary indicators. The expert consensus reached aims to encourage medical institutions at all levels to continuously improve the high-quality research and development and transformation of new TCM originating from the TCM clinical practice in medical institutions and targeted at clinical needs, so as to provide a decision-making basis for the preparation, selection, cultivation, and transformation of new TCM for medical institutions, improve the development efficiency of new TCM, and precisely respond to the public medication needs.
Medicine, Chinese Traditional/standards* ; Humans ; Consensus ; Drugs, Chinese Herbal/therapeutic use* ; Surveys and Questionnaires

Post-stroke cognitive impairment(PSCI)is a prevalent functional impairments following stroke that seriously affects patients'quality of life and daily activities.Studies indicate a close relationship between intestinal microflora dysbiosis and central nervous system diseases.Intestinal microflora profoundly impacts on human physiological health,contributing to the stability of nervous,metabolic and immune systems through regulation of the gut-brain axis.An increasing number of studies confirmed the important role of the gut microbiome-gut-brain axis in the occurrence and development of stroke and its associated PSCI,and regulation of microbiome-gut-brain could be potential target to treatment of PSCI.This review summarizes research progress on gut microbiome-gut-brain axis and PSCI to provide a reference for exploration of related mechanisms and clinical prevention and treatment strategies.

Objective: To investigate the effects of 3-phosphoinositide-dependent protein kinase-1(PDK1) on the purkinje cells(PCs) in aging mice. Methods: The footprint test, elevated beam-walk test and rotarod test were used to measure the gait traits, motor balance and motor coordination of mice. Immunoflourescence was used to detect the structure of the cerebellum and the morphology of cells in the cerebellum. The expression level of PDK1, protein kinase C gamma(PKCγ) and protein kinase B(also known as AKT) and the phosphorylation of ribosomal protein S6(rpS6) in the cerebellum were detected by Western blot. Results: The mice showed motor defects in the overlap between forelimb and hindlimb, motor balance and motor coordination ability in an age-dependent manner. Furthermore, the cerebellum and the soma size of the PCs decreased in an age-dependent manner. However, the density of the PCs was not affected by age. Additionally, the expression level of the PDK1, PKCγ, AKT and the phosphorylation of rpS6 in the cerebellum were reduced with age. Conclusion The cerebellar size and the cell soma size of PCs decrease in the old mice. These effects may contribute to the reduction of the expression of PKCγ and AKT and the phosphorylation of rpS6 in the old mice, ultimately affecting the cerebellar motor coordination.

Objective To explore the relationship and internal path between activities of daily living(ADL),sleep quality and mental health of community elderly people in Shanghai.Methods A questionnaire survey was conducted among community residents aged 60 years and older seeing doctors in community health care center of five streets in Shanghai during Sept to Dec,2021 using convenience sampling.Activities of Daily Living(ADL),Pittsburgh Sleep Quality Index(PSQI)and 10-item Kessler Psychological Distress Scale(K10)were adopted in the survey.Single factor analysis,correlation analysis and multiple linear regression were used to analyze the data.The effect relationship between the variables was tested using Bootstrap's mediated effects test.Results A total of 1 864 participants were included in the study.The average score was 15.53±4.47 for ADL,5.60±3.71 for PSQI and 15.50±6.28 for K10.The rate of ADL impairment,poor sleep quality,poor and very poor mental health of the elderly were 23.6%,27.3%,11.9%and 4.9%,respectively.ADL and sleep quality were all positively correlated with mental health(r=0.321,P＜0.001;r=0.466,P＜0.001);ADL was positively correlated with sleep quality(r=0.294,P＜0.001).Multiple linear results of factors influencing mental health showed that ADL(β= 0.457,95%CI:0.341-0.573),sleep quality(β =0.667,95%CI:0.598-0.737)and mental health were positively correlated(P＜0.001).Sleep quality partially mediated the relationship between ADL and mental health(95%CI:0.078-0.124)with an effect size of 33.0%.Conclusion Sleep quality is a mediator between ADL and mental health among community elderly people.Improving ADL and sleep quality may improve mental health in the population.

Osteoporosis leads to an imbalance in bone remodelling, where bone resorption is greater than bone formation and osteoclast degradation increases, resulting in severe bone loss. Autophagy is a lysosomal degradation pathway that regulates the proliferation, differentiation, and apoptosis of various bone cells (including osteoblasts, osteoclasts, and osteoclasts), and is deeply involved in the bone remodelling process. In recent years, the role of autophagy in the progression of osteoporosis and related bone metabolic diseases has received more and more attention, and it has become a research hotspot in this field. Summarising the existing studies, it is found that senile osteoporosis is the result of a combination of factors. On the one hand, it is the imbalance of bone remodelling and the increase of bone resorption/bone formation ratio with ageing, which causes progressive bone loss. On the other hand, aging leads to a general decrease in the level of autophagy, a decrease in the activity of osteoblasts and osteoclasts, and an inhibition of osteogenic differentiation. The lack of oestrogen leads to the immune system being in a low activation state, and the antioxidant capacity is weakened and inflammatory response is increased, inducing autophagy-related proteins to participate in the transmission of inflammatory signals, excessive accumulation of reactive oxygen species (ROS) in the skeleton, and negatively regulating bone formation. In addition, with aging and the occurrence of related diseases, glucocorticoid treatments also mediate autophagy in bone tissue cells, contributing to the decline in bone strength. Exercise, as an effective means of combating osteoporosis, improves bone biomechanical properties and increases bone density. It has been found that exercise induces oxidative stress, energy imbalance, protein defolding and increased intracellular calcium ions in the organism, which in turn activates autophagy. In bone, exercise of different intensities activates messengers such as ROS, PI3K, and AMP. These messengers signal downstream cascades, which in turn induce autophagy to restore dynamic homeostasis in vivo. During exercise, increased production of AMP, PI3K, and ROS activate their downstream effectors, AMPK, Akt, and p38MAPK, respectively, and these molecules in turn lead to activation of the autophagy pathway. Activation of AMPK inhibits mTOR activity and phosphorylates ULK1 at different sites, inducing autophagy. AMPK and p38 up-regulate per-PGC-1α activity and activate transcription factors in the nucleus, resulting in increased autophagy and lysosomal genes. Together, they activate FoxOs, whose transcriptional activity controls cellular processes including autophagy and can act on autophagy key proteins, while FoxOs proteins are expressed in osteoblasts. Exercise also regulates the expression of mTORC1, FoxO1, and PGC-1 through the PI3K/Akt signalling pathway, which ultimately plays a role in the differentiation and proliferation of osteoblasts and regulates bone metabolism. In addition, BMPs signaling pathway and long chain non-coding RNAs also play a role in the proliferation and differentiation of osteoblasts and autophagy process under exercise stimulation. Therefore, exercise may become a new molecular regulatory mechanism to improve osteoporosis through the bone autophagy pathway, but the specific mechanism needs to be further investigated. How exercise affects bone autophagy and thus prevents and treats bone-related diseases will become a future research hotspot in the fields of biology, sports medicine and sports science, and it is believed that future studies will further reveal its mechanism and provide new theoretical basis and ideas.

Objective We aimed to assess the serum levels of the glycolysis-related protein hypoxia-inducible factor-1α(HIF-1α)and cytokines in patients with relapsing-remitting multiple sclerosis(RRMS)before and after treatment with the traditional Chinese medicine Yishen Daluo Decoction,as well as their correlation with clinical parameters,and explore the immune regulatory mechanism of Yishen Daluo Decoction on multiple sclerosis.Methods Twenty-eight patients with RRMS in remission recruited from May 2018 to January 2022 in the Multiple Sclerosis Clinic at Dongzhimen Hospital,Beijing University of Chinese Medicine were retrospectively included.Comparisons were made with paired samples from 13 of them before and after Yishen Daluo Decoction treatment.A total of 20 gender-and age-matched healthy controls(HCs)were also recruited.Clinical information was collected from all of the subjects,and the neurological impairments of RRMS patients were assessed with the Expanded Disability Status Scale(EDSS)score.ELISA and SP-X multiplex cytokine assays were used to measure the serum levels of HIF-1 α and 10 cytokines(IL-1β,IL-4,IL-5,IL-6,IL-8,IL-10,IL-12p70,IL-22,IFN-γ,and TNF-α),respectively.Spearman's method was used to analyze the correlation between the serum levels of HIF-1α and cytokines,and the correlation between the serum levels of HIF-1α and cytokines and patients'clinical indicators,including disease duration,the number of attacks,and the EDSS score.Results Serum HIF-1α,IL-4,IL-6,IL-8,IL-10,IL-12p70,IFN-γ,and TNF-α levels in the RRMS group were significantly higher than those in the HC group(P＜0.05).Serum levels of HIF-1α,IL-4,IL-6,and IL-12p70 in the Yishen Daluo Decoction-pre group were significantly higher than those in the Yishen Daluo Decoction-post group(P＜0.05).In addition,the serum HIF-1α level was positively correlated with IL-6(r=0.452,P=0.016)and TNF-α(r=0.524,P=0.004)levels in patients with RRMS.The IFN-γ level was negatively correlated with the EDSS score(r=-0.423,P=0.025),the IL-4 level was negatively correlated with disease duration(r=-0.385,P=0.043),and the TNF-α level was positively correlated with disease duration(r=0.397,P=0.037).Conclusion The regulatory mechanism of Yishen Daluo Decoction on immune imbalance in RRMS may be related to its ability to reduce the serum levels of the glycolysis-related protein HIF-1α in RRMS patients.It is also related to the levels of various inflammatory cytokines.

AIM: Yi Qi Yang Yin Decoction (YQYY) has been used to treat patients with rheumatoid arthritis (RA) and achieved good results in clinical applications, but the mechanism still needs to be explored. The purpose was to investigate the mechanism of YQYY in rats with collagen-induced arthritis. METHODS: The possible treatment target and signaling pathway were predicted by bioinformatics and network pharmacology analysis. Elisa,quantitative real-time polymerase chain reaction, and Western Blot were used to verify the mechanism of YQYY in treating RA. RESULTS: FABP4, MMP9 and PTGS2 were the most common predicational therapeutic targets. The results of pathology and CT showed that YQYY could improve ankle swelling, synovitis and bone erosion in CIA rats. Compared with the model group, YQYY or YQYY+MTX can significantly reduce the secretion of CRP, TNF-α, IL-1β and FABP4 in serum of CIA rats (P<0.05 or P<0.01), meanwhile, reduce the mRNA of FABP4, IKKα and p65 in synovial tissue (P<0.01), PPARγ was increased (P<0.01). YQYY could significantly reduce the expression of FABP4, IKKα and pp65 proteins in synovium, and suppress the activate of NF - κB signaling pathway. CONCLUSION: FABP4, MMP9 and PTGS2 may be the targets of YQYY decoction for RA treatment. YQYY can relieve joint symptoms in CIA rats, and regulate inflammation by inhibiting FABP4 / PPARγ/NF - κB signaling pathway, playing a role in the treatment of RA. The effect of YQYY combined with MTX was more prominent. This provided experimental evidence for the efficacy of YQYY decoction in clinical practice.