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.

Introduction: The 2021 IDF-DAR risk calculator had been previously evaluated in multiple studies and subsequently widely accepted and applied in clinical practice as a practical standardized tool for patient risk stratification. Recently updated, the 2026 IDF-DAR Risk calculator enables a more individualized, evidence-related evaluation of patientrelated and disease-related risk factors, incorporating modern diabetes technologies, including continuous glucose monitoring (CGM), automated insulin delivery (AID) systems, and advanced insulin formulations to enhance risk stratification. This tool allows medical professionals to tailor Ramadan practices based on overall factors toward promoting safe fasting. Methodology: This prospective multicentre observational study recruited adults with Type 1 and Type 2 diabetes attending public hospitals nationwide. People with diabetes (PwD) intending to perform Ramadan fasting were invited to participate and assessed using the 2026 IDF-DAR Risk Calculator in the 6-week pre-Ramadan period between 30th January and 19th March 2026. Results: A total of 458 PwD were evaluated and stratified into low (15.7%), moderate (41%), and high risk (43.3%) categories. Most participants had Type 2 diabetes (83.6%), with 60.3% having a disease duration exceeding 10 years and 43% exhibiting poor glycemic control (hemoglobin A1c >9%). Insulin therapy was used by 76.4% of participants, including two individuals with Type 1 diabetes using AID systems. Most participants reported no recent hypoglycemia (76.4%), 81.0% performed glucose monitoring, and 3.3% used CGM. Severe comorbidities were uncommon, with 1.1% having unstable macrovascular disease and 4.4% advanced chronic kidney disease (estimated glomerular filtration rate <30). Notably, 72.2% received structured Ramadan education. Conclusion Majority of PwD attending tertiary diabetes clinics were in the moderate- to high-risk category and intended to fast despite medical advice against fasting in some cases. Although most participants were on insulin therapy, hypoglycemia was low in the pre-Ramadan period. Integration of modern technologies, advanced insulin therapies, and structured education may support safer fasting practices.
Risk Assessment ; Diabetes Mellitus ; Hospitals ; Fasting

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.

objective:To investigate the factors influencing failure of preoperative optimisation with exclusive enteral nutrition(EEN)in patients with Crohn's disease(CD)and to construct a predictive model.Methods:Clinical data of 161 patients with Crohn's disease who underwent surgical treatment after preoperative EEN optimization at the Inflammatory Bowel Disease Center of General Surgery of the Eastern Theater General Hospital from June 2021 to November 2023 were retrospectively analyzed.Patients were divided into two groups according to the preoperative EEN optimisation effect:optimisation success and optimisation failure.Logistic regression analysis was used to determine the factors influencing optimisation failure,and a column line graphical model was constructed using R4.4.0 software.Results:After at least 4 weeks of EEN treatment,a total of 44 patients(27.33%)failed preoperative optimization.Multifactorial analysis showed that FC>500 μg/g and use of corticosteroids were independent risk factors for failure of preoperative optimization,and an increase in prealbumin after 1 week of treatment was a protective factor for successful preoperative optimization.Based on the results of the multivariate analysis,a column graph was constructed,and the C-index was 0.873(95%CI=0.783～0.964).The calibration curve shows that the probability of failure predicted by the nomogram model prior to optimization is in good agreement with the actual probability.The clinical decision curve confirms that the risk threshold is between 0.03～0.96,and the nomogram model can be used to predict the failure of preoperative EEN optimization over other treatment options.Conclusion:FC>500μg/g and history of corticosteroid use were independent risk factors for failure of preoperative optimization,and an increase in prealbumin after 1 week of treatment was a protective factor for successful preoperative optimization.The nomogram constructed on the basis of these results has a good predictive value and is clinically applicable.

Integrated metabolomic and lipidomic profiling,utilizing liquid chromatography coupled with high-resolution mass spectrometry(LC-HRMS),has emerged as a pivotal strategy for biomarker discovery.However,the inherent polarity disparity between metabolites and lipids complicates simultaneous analysis.To address this,a dual-stationary phase polarity-extended liquid chromatography(PELC)system was developed,which surpassed conventional one-dimensional LC(1D-LC)by enabling comprehensive coverage of both polar and non-polar compounds within a single injection.This system enhanced chromatographic resolution,peak capacity,and throughput while minimizing analytical variability.Extracellular vesicles(EVs),lipid bilayer-enclosed nanoparticles ubiquitously present in biofluids,had gained prominence as reservoirs of cancer biomarkers due to their cargo stability and pathophysiological relevance.Herein,the application of PELC-HRMS for concurrent metabolome-lipidome profiling in EVs was pioneered.A total of 193 metabolites were identified using this technique coupled with MS-DIAL software and Human Metabolome Database.Subsequently,this technique was employed to explore potential biomarkers for prostate cancer(PCa).Multivariate analysis identified 17 differentially abundant metabolites in PCa,implicating dysregulated pathways including purine metabolism,starch and sucrose metabolism,galactose metabolism,cysteine and methionine metabolism,and biosynthesis of unsaturated fatty acids.Notably,creatine(AUC=0.92)and DG 42:5(AUC=0.80)demonstrated robust diagnostic efficacy,attributable to their broad polarity ranges and EV-specific enrichment.This study established PELC as a high-fidelity platform for multi-omics integration in complex biospecimens,advancing mechanistic insights into metabolic rewiring and disease pathophysiology.

OBJECTIVE: To retrospectively analyze the clinical data of newly diagnosed acute myeloid leukemia (AML) patients treated with venetoclax combined with azacitidine (Ven/Aza) or standard "3+7" regimen and similar regimens, collect real-world study data, compare the treatment response and adverse events between the two regimens, as well as perform survival analysis. METHODS: To retrospectively analyze the efficacy, survival, and adverse reactions of newly diagnosed AML patients treated with Ven/Aza (24 cases) and "3+7" regimens (117 cases ) in our hospital from September 2009 to March 2023, as well as factors influencing outcomes. A propensity score matching (PSM) was performed on age and Eastern Cooperative Oncology Group performance status (ECOG PS) to obtain a 1:1 matched cohort of 20 pairs, and the efficacy and survival before and after the matching were compared. RESULTS: The median age of patients in the Ven/Aza group was 69 years, while that in the "3+7" group was 56 years (P <0.001). Objective remission rate (ORR) was 62.5% in Ven/Aza group and 74.8% in "3+7" group (P >0.05). The median overall survival (OS) in the Ven/Aza group was 522 days, while that in the "3+7" group was 1 002 days (P >0.05). After controlling the two variables of age and ECOG PS, a PSM cohort of 20 pairs was obtained, in which the ORR was 65% in Ven/Aza group and 60% in "3+7" group (P >0.05). The median OS was 522 days and 629 days, and median progression-free survival (PFS) was 531 days and 198 days between the two groups, respectively. There were no statistically significant differences in OS and PFS between the two groups (both P >0.05). Additionally, the incidence of adverse events in the Ven/Aza group was significantly reduced. CONCLUSION The overall cohort shows that the "3+7" regimen has advantages in efficacy and survival, but Ven/Aza regimen is relatively safer. After performing PSM on age and ECOG PS, the Ven/Aza group showed improved efficacy, and a longer median PFS compared to "3+7" group.
Humans ; Leukemia, Myeloid, Acute/drug therapy* ; Retrospective Studies ; Sulfonamides/administration & dosage* ; Azacitidine/administration & dosage* ; Bridged Bicyclo Compounds, Heterocyclic/administration & dosage* ; Aged ; Middle Aged ; Male ; Female ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Treatment Outcome

OBJECTIVE: To establish a three-dimensional finite element model of a digital wire loop space maintainer for the mandible and primary tooth loss, in order to investigate the stress, deformation, and shear force experienced by patients with the loss of the second primary molar when wearing the wire loop space maintainer. METHODS: Cone beam computed tomography (CBCT) scans were performed on the patients to create a digital model of the mandible with the absence of the second primary molar using Mimics 21.0 software. A digital model integrating the crown's retention and the wire loop structure of the full crown and ring wire loop space maintainer was constructed using pediatric space maintainer design software, utilizing three different materials: cobalt-chromium alloy, polyether ether ketone (PEEK), and titanium alloy. In ANSYS Work Beach 2023 R2 software, vertical loads of 70 N, tilted 45° along the long axis of the tooth loads of 70 N, and a 10 N load on the surface of the wire loop were applied to the occlusal surfaces of models 46 and 84, simulating centric and lateral occlusions during chewing with the wire loop space maintainer in place. The stress states of the wire loop space maintainer and supporting teeth were analyzed. RESULTS: Under various loading conditions, the maximum principal stress of the ring wire loop space maintainer was significantly lower than that of the full crown. Stress contour maps indicated that the peak of the maximum principal stress occurred at the junction of the wire loop and crown structure, indicating that this area was more susceptible to fracture. The ring wire loop space maintainer made from PEEK material exhibited the lowest maximum shear stress on the internal organizational surfaces, with equivalent stresses of 23.18 MPa and 36.35 MPa for models 46 and 84, respectively. Stress contour maps demonstrated that the maximum stress on tooth 46 was located at its mesial, while the maximum stress on tooth 84 was situated near the root area on its distal, in contact with the wire loop space maintainer. CONCLUSION In cases of second primary molar loss, wearing the digital ring wire loop space maintainer can effectively distribute stress, and the ring wire loop space maintainer made from PEEK material reduces the stress experienced by supporting teeth to some extent, demonstrating its superiority in clinical application.
Finite Element Analysis ; Humans ; Tooth, Deciduous ; Cone-Beam Computed Tomography ; Space Maintenance, Orthodontic/methods* ; Imaging, Three-Dimensional ; Orthodontic Wires ; Dental Stress Analysis ; Mandible ; Stress, Mechanical

Debates persist regarding the efficacy and safety of azvudine, particularly its real-world outcomes. This study involved patients aged ≥60 years who were admitted to 25 hospitals in mainland China with confirmed SARS-CoV-2 infection between December 1, 2022, and February 28, 2023. Efficacy outcomes were all-cause mortality during hospitalization, the proportion of patients discharged with recovery, time to nucleic acid-negative conversion (T _NANC), time to symptom improvement (T _SI), and time of hospital stay (T _HS). Safety was also assessed. Among the 5884 participants identified, 1999 received azvudine, and 1999 matched controls were included after exclusion and propensity score matching. Azvudine recipients exhibited lower all-cause mortality compared with controls in the overall population (13.3% vs. 17.1%, RR, 0.78; 95% CI, 0.67-0.90; P = 0.001) and in the severe subgroup (25.7% vs. 33.7%; RR, 0.76; 95% CI, 0.66-0.88; P < 0.001). A higher proportion of patients discharged with recovery, and a shorter T _NANC were associated with azvudine recipients, especially in the severe subgroup. The incidence of adverse events in azvudine recipients was comparable to that in the control group (2.3% vs. 1.7%, P = 0.170). In conclusion, azvudine showed efficacy and safety in older patients hospitalized with COVID-19 during the SARS-CoV-2 omicron wave in China.

Transarterial radioembolization (TARE) is a widely utilized therapeutic approach for hepatocellular carcinoma (HCC), however, the clinical implementation is constrained by the stringent preparation conditions of radioembolization agents. Herein, we incorporated the superstable homogeneous iodinated formulation technology (SHIFT), simultaneously utilizing an enhanced solvent form in a carbon dioxide supercritical fluid environment, to encapsulate radionuclides (such as ¹³¹I,¹⁷⁷Lu, or ¹⁸F) with lipiodol for the preparation of radiolipiodol. The resulting radiolipiodol exhibited exceptional stability and ultra-high labeling efficiency (≥99%) and displayed notable intratumoral radionuclide retention and in vivo stability more than 2 weeks following locoregional injection in subcutaneous tumors in mice and orthotopic liver tumors in rats and rabbits. Given these encouraging findings, ¹⁸F was authorized as a radiotracer in radiolipiodol for clinical trials in HCC patients, and showed a favorable tumor accumulation, with a tumor-to-liver uptake ratio of ≥50 and minimal radionuclide leakage, confirming the feasibility of SHIFT for TARE applications. In the context of transforming from preclinical to clinical screening, the preparation of radiolipiodol by SHIFT represents an innovative physical strategy for radionuclide encapsulation. Hence, this work offers a reliable and efficient approach for TARE in HCC, showing considerable promise for clinical application (ChiCTR2400087731).