Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by the selective loss of dopaminergic neurons in the substantia nigra pars compacta and the pathological accumulation ofα‑synuclein. Although extensive progress has been made in elucidating its pathogenesis, current therapeutic approaches remain largely symptomatic, and effective disease-modifying treatments are still unavailable. Increasing evidence indicates that PD is driven by the interaction of multiple pathological processes, including neuroinflammation, iron homeostasis dysregulation and ferroptosis, endoplasmic reticulum (ER) stress, mitochondrial dysfunction, oxidative stress, and impaired protein homeostasis, which together contribute to neuronal vulnerability and degeneration. Fibroblast growth factors (FGFs) comprise a family of 22 ligands that play important roles in neural development, stress responses, metabolic regulation, and the maintenance of nervous system homeostasis. Recent studies have shown that several FGF family members, such as FGF1, FGF2, FGF9, and FGF21, exert neuroprotective effects in cellular and animal models of PD. These effects include the regulation of inflammatory responses, oxidative stress, iron homeostasis, cellular stress adaptation, and neuronal survival. Compared with therapeutic strategies targeting a single pathogenic pathway, FGFs appear to influence multiple disease-related processes, suggesting their potential relevance to the complex pathophysiology of PD. Experimental evidence indicates that altered FGF signaling may contribute to dopaminergic neuron dysfunction through the coordinated regulation of several interconnected mechanisms. FGFs have been reported to modulate neuroinflammation by affecting the activation of microglia and astrocytes, thereby influencing the inflammatory environment in the central nervous system. In addition, FGFs are involved in the regulation of iron homeostasis and ferroptosis, partly through antioxidant signaling pathways associated with NRF2, SLC7A11, and GPX4. Moreover, FGFs can alleviate ER stress and mitochondrial dysfunction by activating intracellular signaling pathways such as PI3K/AKT, AMPK-PGC-1α, as well as SIRT1-dependent programs, which support cellular energy metabolism and redox balance. Recent advances in single-cell and spatial transcriptomic studies further suggest that FGF signaling is not limited to neuron-intrinsic mechanisms but also involves interactions among different glial cell types. Altered FGF ligand-receptor communication between astrocytes and oligodendrocytes has been observed in PD models and is associated with increased susceptibility of dopaminergic neurons to oxidative stress and ferroptosis. These findings indicate that the biological effects of FGFs are influenced by cell type and disease stage and may vary under different pathological conditions. In this review, we summarize recent progress in understanding the roles of FGF family members in PD, with a focus on their involvement in iron homeostasis dysregulation and ferroptosis, neuroinflammation, cellular stress responses, and neuronal protection and regeneration. By integrating current evidence, this review aims to provide a clearer understanding of how FGFs participate in PD pathogenesis and to offer a theoretical basis for future studies exploring their potential value in disease-modifying therapeutic strategies.

BACKGROUND:According to existing clinical studies,vertebroplasty treatment with both the external pedicle approach and the pedicle approach can improve the pain and quality of life of patients with spinal compression fractures.Compared with the pedicle approach,the external pedicle approach has a freer puncture angle,and good bone cement dispersion effect can be obtained by adjusting the puncture angle. OBJECTIVE:To compare the impact of vertebroplasty through individualized unilateral external pedicle approach and bilateral pedicle approach on the treatment of spinal compression fractures by quantifying the dispersion effect of bone cement. METHODS:A total of 80 patients with thoracolumbar compression fracture were divided into two groups by random number table method.The bilateral pedicle group(n=40)underwent vertebroplasty through a bilateral pedicle approach,while the unilateral external pedicle group(n=40)underwent individualized vertebroplasty through a unilateral external pedicle approach.Anteroposterior and lateral X-rays of the affected vertebrae from two groups of patients were photographed to assess effect and type of bone cement dispersion within 3 days after surgery.Visual analog scale score,tenderness threshold around fracture,and Oswestry dysfunction index were assessed before,1,7 days,and 1 month after surgery. RESULTS AND CONCLUSION:(1)Dispersion effect of bone cement in unilateral external pedicle group was better than that in bilateral pedicle group(P<0.001),and the amount of bone cement perfusion was higher than that in bilateral pedicle group(P<0.001).In the bilateral pedicle group,the bone cement dispersion types were mainly concentrated in type Ⅰ and type Ⅲ,while in the unilateral external pedicle group,the bone cement dispersion types were mainly concentrated in type I and type Ⅱ,and there was a significant difference in bone cement dispersion types between the two groups(P<0.001).(2)Postoperative visual analog scale scores and Oswestry disability index of both groups were lower than those before surgery(P<0.001),and postoperative tenderness threshold around fracture showed a trend of decreasing first and then increasing.At the same time point after treatment,there were no significant differences in visual analog scale score,Oswestry disability index,and tenderness threshold around fracture between the two groups(P>0.05).(3)The results indicate that individualized vertebroplasty via unilateral external pedicle approach can achieve better bone cement dispersion,and the treatment effect is consistent with the vertebroplasty via classical bilateral pedicle approach.

The purpose of this study was to clarify the effect of Huotan Jiedu Tongluo Decoction on atherosclerosis(AS) injury in ApoE~(-/-) mice by regulating the ferroptosis pathway. Seventy-five ApoE~(-/-) mice were randomly divided into model group, low-, medium-, and high-dose of Huotan Jiedu Tongluo Decoction groups, and evolocumab group(n=15), and 15 C57BL/6J mice were selected as the blank group. Mice in the blank group were fed with a normal diet, and those in the other groups were fed with a high-fat diet to induce AS. From the 9th week, mice in Huotan Jiedu Tongluo Decoction groups were administrated with Huotan Jiedu Tongluo Decoction at corresponding doses by gavage, and those in the blank group and the model group were given an equal volume of distilled water. Mice in the evolocumab group were treated with evolocumab 18.2 mg·kg~(-1 )by subcutaneous injection every 2 weeks. After 8 weeks of continuous intervention, oil red O staining and hematoxylin-eosin(HE) staining were employed to observe the lipid deposition and plaque formation in the aortic root. Masson staining was used to evaluate the collagen content in the aortic root. The serum levels of total cholesterol(TC), triglycerides(TG), high-density lipoprotein cholesterol(HDL-C), and low-density lipoprotein cholesterol(LDL-C) were determined by biochemical kits. The levels of Fe~(2+), superoxide dismutase(SOD), malondialdehyde(MDA), and glutathione(GSH) in the aorta were measured by colorimetry. The protein and mRNA levels of nuclear factor erythroid 2-related factor 2(Nrf2), glutathione peroxidase 4(GPX4), solute carrier family 7 member 11(SLC7A11), and acyl-CoA synthetase long chain family member 4(ACSL4) in the aorta were detected by Western blot and RT-qPCR, respectively. The expression of Nrf2, GPX4, and SLC7A11 was localized by immunofluorescence. The results showed that low-, medium-, and high-dose Huotan Jiedu Tongluo Decoction reduced the plaque formation of aortic root and increased the collagen content in AS mice. At the same time, Huotan Jiedu Tongluo Decoction improved the lipid metabolism by lowering the levels of TC, LDL-C, and TG and elevating the level of HDL-C in the serum. Huotan Jiedu Tongluo Decoction enhanced the antioxidant capacity by elevating the levels of GSH and SOD and lowering the level of MDA in the aorta and inhibiting the accumulation of Fe~(2+) in the aorta. In addition, Huotan Jiedu Tongluo Decoction up-regulated the protein and mRNA levels of Nrf2, GPX4, and SLC7A11, while down-regulating the protein and mRNA levels of ACSL4. In summary, Huotan Jiedu Tongluo Decoction can effectively alleviate AS lesions in ApoE~(-/-) mice by activating the Nrf2/GPX4 pathway, reducing lipid peroxidation, and inhibiting ferroptosis.
Animals ; Ferroptosis/drug effects* ; Atherosclerosis/metabolism* ; Drugs, Chinese Herbal/administration & dosage* ; NF-E2-Related Factor 2/genetics* ; Mice ; Mice, Inbred C57BL ; Apolipoproteins E/metabolism* ; Male ; Phospholipid Hydroperoxide Glutathione Peroxidase/genetics* ; Signal Transduction/drug effects* ; Humans ; Mice, Knockout

INTRODUCTION: The diagnosis of sarcopenia relies on key indicators such as handgrip strength, walking speed and muscle mass. Developing a composite index that integrates these measures could enhance clinical evaluation in older adults. This study aimed to standardise and combine these metrics to establish a z score for the sarcopenia composite index (ZoSCI) tailored for the ageing population. Additionally, we explore the risk factors associated with ZoSCI to provide insights into early prevention and intervention strategies. METHOD: This retrospective study analysed data between January 2017 and December 2021 from an elderly health programme in Taiwan, applying the Asian Working Group for Sarcopenia criteria to assess sarcopenia. ZoSCI was developed by standardising handgrip strength, walking speed and muscle mass into z scores and integrating them into a composite index. Receiver operating characteristic (ROC) curve analysis was used to determine optimal cut-off values, and multiple regression analysis identified factors influencing ZoSCI. RESULTS: Among the 5047 participants, the prevalence of sarcopenia was 3.7%, lower than the reported global prevalence of 3.9-15.4%. ROC curve analysis established optimal cut-off points for distinguishing sarcopenia in ZoSCI: -1.85 (sensitivity 0.91, specificity 0.88) for males and -1.97 (sensitivity 0.93, specificity 0.88) for females. Factors associated with lower ZoSCI included advanced age, lower education levels, reduced exercise frequency, lower body mass index and creatinine levels. CONCLUSION This study introduces ZoSCI, a new compo-site quantitative indicator for identifying sarcopenia in older adults. The findings highlight specific risk factors that can inform early intervention. Future studies should validate ZoSCI globally, with international collaborations to ensure broader applicability.
Humans ; Sarcopenia/physiopathology* ; Male ; Aged ; Female ; Retrospective Studies ; Hand Strength ; Taiwan/epidemiology* ; ROC Curve ; Aged, 80 and over ; Risk Factors ; Walking Speed ; Geriatric Assessment/methods* ; Prevalence ; Muscle, Skeletal ; Middle Aged

INTRODUCTION: The primary objective of this guideline is to establish evidence-based recommendations for the clinical use of parenteral nutrition (PN) in adult patients within the acute hospital setting in Singapore. METHOD: An expert workgroup, consisting of healthcare practitioners actively involved in clinical nutrition support across all public health institutions, systematically evaluated existing evidence and addressed clinical questions relating to PN therapy. RESULTS: This clinical practice guideline developed 30 recommendations for PN therapy, which cover these key aspects related to PN use: indications, patient assess-ment, titration and formulation of PN bags, access routes and devices, and monitoring and management of PN-related complications. CONCLUSION This guideline provides recommendations to ensure appropriate and safe clinical practice of PN therapy in adult patients within the acute hospital setting.
Humans ; Singapore ; Parenteral Nutrition/adverse effects* ; Adult

The current study aimed to clarify the roles of apolipoprotein A5 (ApoA5) and milk fat globule-epidermal growth factor 8 (Mfge8) in regulating myocardial lipid deposition and the regulatory relationship between them. The serum levels of ApoA5 and Mfge8 in obese and healthy people were compared, and the obesity mouse model induced by the high-fat diet (HFD) was established. In addition, primary cardiomyocytes were purified and identified from the hearts of suckling mice. The 0.8 mmol/L sodium palmitate treatment was used to establish the lipid deposition cardiomyocyte model in vitro. ApoA5-overexpressing adenovirus was used to observe its effects on cardiac function and lipids. The expressions of the fatty acid uptake-related molecules and Mfge8 on transcription or translation levels were detected. Co-immunoprecipitation was used to verify the interaction between ApoA5 and Mfge8 proteins. Immunofluorescence was used to observe the co-localization of Mfge8 protein with ApoA5 or lysosome-associated membrane protein 2 (LAMP2). Recombinant rMfge8 was added to cardiomyocytes to investigate the regulatory mechanism of ApoA5 on Mfge8. The results showed that participants in the simple obesity group had a significant decrease in serum ApoA5 levels (P < 0.05) and a significant increase in Mfge8 levels (P < 0.05) in comparison with the healthy control group. The adenovirus treatment successfully overexpressed ApoA5 in HFD-fed obese mice and palmitic acid-induced lipid deposition cardiomyocytes, respectively. ApoA5 reduced the weight of HFD-fed obese mice (P < 0.05), shortened left ventricular isovolumic relaxation time (IVRT), increased left ventricular ejection fraction (LVEF), and significantly reduced plasma levels of triglycerides (TG) and cholesterol (CHOL) (P < 0.05). In myocardial tissue and cardiomyocytes, the overexpression of ApoA5 significantly reduced the deposition of TG (P < 0.05), transcription of fatty acid translocase (FAT/CD36) (P < 0.05), fatty acid-binding protein (FABP) (P < 0.05), and fatty acid transport protein (FATP) (P < 0.05), and protein expression of Mfge8 (P < 0.05), while the transcription levels of Mfge8 were not significantly altered (P > 0.05). In vitro, the Mfge8 protein was captured using ApoA5 as bait protein, indicating a direct interaction between them. Overexpression of ApoA5 led to an increase in co-localization of Mfge8 with ApoA5 or LAMP2 in cardiomyocytes under lipid deposition status. On this basis, exogenous added recombinant rMfge8 counteracted the improvement of lipid deposition in cardiomyocytes by ApoA5. The above results indicate that the overexpression of ApoA5 can reduce fatty acid uptake in myocardial cells under lipid deposition status by regulating the content and cellular localization of Mfge8 protein, thereby significantly reducing myocardial lipid deposition and improving cardiac diastolic and systolic function.
Animals ; Humans ; Mice ; Myocytes, Cardiac/metabolism* ; Obesity/physiopathology* ; Male ; Apolipoprotein A-V/blood* ; Lipid Metabolism/physiology* ; Milk Proteins/blood* ; Myocardium/metabolism* ; Diet, High-Fat ; Antigens, Surface/physiology* ; Mice, Inbred C57BL ; Cells, Cultured ; Female

OBJECTIVE: Observational studies have found associations between inflammatory bowel disease (IBD) and the risk of dementia, including Alzheimer's dementia (AD) and vascular dementia (VD); however, these findings are inconsistent. It remains unclear whether these associations are causal. METHODS: We conducted a meta-analysis by systematically searching for observational studies on the association between IBD and dementia. Mendelian randomization (MR) analysis based on summary genome-wide association studies (GWASs) was performed. Genetic correlation and Bayesian co-localization analyses were used to provide robust genetic evidence. RESULTS: Ten observational studies involving 80,565,688 participants were included in this meta-analysis. IBD was significantly associated with dementia (risk ratio [ RR] =1.36, 95% CI = 1.04-1.78; I ² = 84.8%) and VD ( RR = 2.60, 95% CI = 1.18-5.70; only one study), but not with AD ( RR = 2.00, 95% CI = 0.96-4.13; I ² = 99.8%). MR analyses did not supported significant causal associations of IBD with dementia (dementia: odds ratio [ OR] = 1.01, 95% CI = 0.98-1.03; AD: OR = 0.98, 95% CI = 0.95-1.01; VD: OR = 1.02, 95% CI = 0.97-1.07). In addition, genetic correlation and co-localization analyses did not reveal any genetic associations between IBD and dementia. CONCLUSION Our study did not provide genetic evidence for a causal association between IBD and dementia risk. The increased risk of dementia observed in observational studies may be attributed to unobserved confounding factors or detection bias.
Humans ; Mendelian Randomization Analysis ; Inflammatory Bowel Diseases/complications* ; Dementia/etiology* ; Observational Studies as Topic ; Genome-Wide Association Study

Cognitive frailty, a novel concept in geriatric medicine, has become a focal point of recent research. Dual-task training, which innovatively integrates physical activity with cognitive rehabilitation, has shown promise in simultaneously enhancing motor function and cognitive performance in older adults with cognitive frailty. This review summarizes the concept of dual-task training, its application modalities, and its effectiveness in this population. It also proposes strategies for further implementation, aiming to provide a reference for future research and practical applications of dual-task training in cognitively frail older adults.

Aging is comprehensively influenced by multiple fac-tors such as internal genes,cellular metabolism,external envi-ronment,and lifestyle habits.Among them,epigenetic regula-tion plays a core role.Epigenetic modifications,including DNA methylation,histone modification,heterochromatin remodeling,and non-coding RNA regulation,act in concert with the three-di-mensional genome architecture to precisely regulate gene expres-sion.This review elaborates on the factors influencing epigenetic regulation,as well as the mechanisms of how epigenetics affects the occurrence of organismal aging and the corresponding inter-vention strategies,providing relevant insights for uncovering the mechanisms of aging and preventing/treating aging-related disea-ses.

To determine the optimal cultivation duration and harvest period for cultivated Notopterygium incisum and promote its industrial development, this study established a characteristic chromatographic profile of cultivated N. incisum and employed chemometrics combined with entropy-weighted grey correlation analysis to assess differences in agronomic traits and quality indicators across different cultivation years and harvest periods. By comparing with reference substances, ten common peaks were identified, including chlorogenic acid, p-coumaric acid, ferulic acid, marmesinin, nodakenin, isochlorogenic acid B, notopterol, phenethyl ferulate, isoimperatorin, and falcarindiol. The similarity between the characteristic chromatographic profiles of N. incisum at different cultivation years and the reference profile was all above 0.932. Principal component analysis(PCA) and orthogonal partial least squares discriminant analysis(OPLS-DA) revealed that the quality of 1-to 3-year-old cultivated N. incisum was highly dispersed and unstable, whereas the quality of 4-year-old cultivated N. incisum remained relatively stable across different harvest periods. This suggests that the accumulation of relevant compounds in the medicinal material had reached a plateau, confirming that the optimal cultivation period for N. incisum is four years. Entropy-weighted grey correlation analysis indicated that the quality of 4-year-old cultivated N. incisum across different harvest periods ranked from highest to lowest as follows: November, December, October, August, July, and September, demonstrating that November is the optimal harvest time. The findings of this study establish the suitable cultivation duration and optimal harvest period for N. incisum, providing a scientific basis for cultivation guidance and quality standardization.
Chromatography, High Pressure Liquid/methods* ; Apiaceae/chemistry* ; Entropy ; Chemometrics/methods* ; Drugs, Chinese Herbal/chemistry* ; Principal Component Analysis ; Quality Control