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.

Aim To investigate the effect of Rtv(a P-gp inhibitor and inducer)on the pharmacokinetics of Y101(P-gp substrate)via P-gp.Methods In short-term studies,rats received a single dose of Rtv,where-as in long-term studies they received continuous dosing for seven days.Following this treatment,Y101 was o-rally administered to analyze its blood concentration in rats.Subsequently,the mechanism by which Rtv af-fected Y101 pharmacokinetics was investigated through the everted gut sac model(in vitro),cellular uptake studies,and so on.Results Short-term administra-tion of Rtv significantly increased Y101's AUC,liver-to-plasma partition coefficient,the everted gut sac model(in vitro),and cellular accumulation.Although long-term Rtv treatment had no effect on Y101 pharma-cokinetics or hepatic distribution,it markedly reduced Y101 cellular accumulation in Caco-2 cells,concomi-tant with an upregulation of P-gp expression.Conclu-sions Short-term Rtv administration acts as a compet-itive P-gp inhibitor,enhancing Y101 intestinal absorp-tion and hepatic distribution.In contrast,the plasma pharmacokinetics and hepatic distribution of Y101 are not altered after long-term administration of Rtv,po-tentially attributable to Rtv's dual modulatory effects on P-gp involving both induction and inhibition.Hence,the potential Rtv and Y101 interaction should be close-ly monitored in the clinic.

Objective:To analyze the clinical and ultrasonographic characteristics of papillary thyroid carcinoma(PTC)and explore their correlation with cervical lymph node metastasis(CLNM),thereby constructing a nomogram pre-diction model for assessing the risk of CLNM in PTC.Methods:A total of 553 patients(corresponding to 553 nod-ules)with papillary thyroid carcinoma(PTC),confirmed by postoperative pathology,who underwent ultrasonography and had complete clinical data at the Second Hospital of Shandong University between December 2019 and December 2022,were included.228 patients(228 nodules)hadcervical lymph node metastasis,and 325 patients(325 nodules)were without cervical lymph node metastasis.All patients were categorized into metastasis and non-metastasis groups based on the presence or absence of cervical lymph node metastasis.These groups were then randomly di-vided into training and validation sets in a 7:3 ratio.Differences in clinical and ultrasonographic characteristics between the two groups were compared,and a nomogram was constructed.Results:Univariate analysis revealed statistically significant differences between the metastasis group and the non-metastasis group in terms of age,presence of Hashimoto's thyroiditis,multifocality,taller-than-wide shape,calcification,capsular contact,and blood flow(P<0.05).Logistic regression analysis in the training set indicated that age,presence of Hashimoto's thyroiditis,multifocality,taller-than-wide shape,calcification,and blood flow were associated with lymph node metastasis in papillary thyroid carcinoma(PTC)(P<0.05).These indicators were incorporated into a nomogram model,which demonstrated high predictive performance,good calibration,and significant clinical utility in both the training and validation sets.Conclu-sion:The nomogram prediction model,constructed based on clinical and ultrasonographic features,effectively predicts the risk of cervical lymph node metastasis(CLNM)in patients with papillary thyroid carcinoma(PTC).Patients who were older,had concomitant Hashimoto's thyroiditis,or exhibited a nodule aspect ratio≥1 were less likely to have concurrent CLNM.Conversely,patients presenting with multiple nodules,nodules with microcalcifications,or nodules demonstrating central or rich/peripheral vascularity were more likely to have concurrent CLNM.

Objective:To understand the prevalence of frailty and the importance of its influencing factors in adult population in Shaanxi Province.Methods:The data were from Shaanxi baseline survey of natural population cohort study in northwest China during 2018-2019. The frailty index (FI) was constructed to evaluate the frailty status of the population, and XGboost model combined with Shapley method was used to analyze the importance of the sociodemographic and life behavior factors affecting the prevalence of frailty by gender and age.Results:A total of 25 079 subjects were included, in whom 964 (3.8%) had frailty, and there was no significant difference in the overall prevalence of frailty between women (3.9%) and men (3.8%) ( P=0.629), but there was a gender specific difference in the distribution of FI ( P<0.001), and the proportion of the pre-frailty in men was higher than that in women. The prevalence of frailty increased with age ( P<0.001), the prevalence of frailty were 1.3%, 2.5% and 7.8% in young, middle-aged and elderly women, respectively, and 1.9%, 2.7% and 5.5% in young, middle-aged and elderly men, respectively. Sociodemographic characteristics and lifestyle patterns were both influencing factors for the prevalence of frailty, but their importance varied with gender and age. The top five contributing factors were education level, staying up late, annual family income level, sedentary time and marital status in young women, and staying up late, smoking, annual family income level, sedentary time and drinking in young men. The top five contributing factors were education level, annual family income level, passive exposure to smoking, staying up late, and sedentary time in middle-aged women, and annual family income level, education level, sedentary time, staying up late and drinking in middle-aged men. The top five contributing factors were annual family income level, passive exposure to smoking, sedentary time, marital status, and smartphone use in elderly women, and education level, annual family income level, smoking, smartphone use and sedentary time in elderly men. Conclusions:There are gender specific differences in the distribution of FI in Shaanxi. The prevalence of frailty increased with age, but young and middle-aged people also have frailty risk. The prevalence of frailty in young men was mainly related to unhealthy life behaviors, such as staying up late, smoking, sedentary behavior and drinking, while the prevalence of frailty in middle-aged and elderly men and women were more affected by sociodemographic factors, such as education level, economic status and marital status.

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

Jiuwei Xifeng Granules have become a Chinese patent medicine in the market. Because the formula contains Os Draconis, a top-level protected fossil of ancient organisms, the formula was to be improved by replacing Os Draconis with Ostreae Concha. To evaluate whether the improved formula has the same effectiveness and safety as the original formula, a randomized, double-blind, parallel-controlled, equivalence clinical trial was conducted. This study enrolled 288 tic disorder(TD) of children and assigned them into two groups in 1∶1. The treatment group and control group took the modified formula and original formula, respectively. The treatment lasted for 6 weeks, and follow-up visits were conducted at weeks 2, 4, and 6. The primary efficacy endpoint was the difference in Yale global tic severity scale(YGTSS)-total tic severity(TTS) score from baseline after 6 weeks of treatment. The results showed that after 6 weeks of treatment, the declines in YGTSS-TSS score showed no statistically significant difference between the two groups. The difference in YGTSS-TSS score(treatment group-control group) and the 95%CI of the full analysis set(FAS) were-0.17[-1.42, 1.08] and those of per-protocol set(PPS) were 0.29[-0.97, 1.56], which were within the equivalence boundary [-3, 3]. The equivalence test was therefore concluded. The two groups showed no significant differences in the secondary efficacy endpoints of effective rate for TD, total score and factor scores of YGTSS, clinical global impressions-severity(CGI-S) score, traditional Chinese medicine(TCM) response rate, or symptom disappearance rate, and thus a complete evidence chain with the primary outcome was formed. A total of 6 adverse reactions were reported, including 4(2.82%) cases in the treatment group and 2(1.41%) cases in the control group, which showed no statistically significant difference between the two groups. No serious suspected unexpected adverse reactions were reported, and no laboratory test results indicated serious clinically significant abnormalities. The results support the replacement of Os Draconis by Ostreae Concha in the original formula, and the efficacy and safety of the modified formula are consistent with those of the original formula.
Adolescent ; Child ; Child, Preschool ; Female ; Humans ; Male ; Double-Blind Method ; Drugs, Chinese Herbal/therapeutic use* ; Tic Disorders/drug therapy* ; Treatment Outcome

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

This study reports the diagnosis and treatment of six cases of post-transplant lymphoproliferative disorder (PTLD) in liver transplant recipients, confirmed at the Affiliated Hospital of Qingdao University between August 2017 and May 2023. The report includes details on anti-rejection therapy, Epstein-Barr virus (EBV) and cytomegalovirus (CMV) infections, imaging findings, histopathological results, treatment courses, and prognoses. By summarizing the clinical experience in the diagnosis and management of PTLD following liver transplantation, this study aims to provide valuable insights and references for the clinical diagnosis and treatment of this condition.