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.

ObjectiveTo construct a risk prediction model for frequent acute exacerbations of chronic obstructive pulmonary disease （COPD） under disease-syndrome combination， thus providing decision support for precise clinical intervention. MethodsA total of 2 029 patients with acute exacerbations of COPD admitted to the First Affiliated Hospital of Anhui University of Chinese Medicine from January 2020 to August 2024 were retrospectively included. These patients were classified into groups of frequent acute exacerbations （≥2 times/year） and infrequent acute exacerbations （<2 times/year） according to the hospitalization times per year. Risk factors were screened by LASSO regression combined with logistic regression， and a nomogram model was constructed. The model performance was assessed based on the area under the curve （AUC）， calibration curves， and decision curve analysis （DCA）. ResultsThe differences in baseline characteristics between the frequent acute exacerbations group （1 196 cases） and infrequent acute exacerbations group （833 cases） were not statistically significant. LASSO regression combined with multivariate logistic regression screened the following independent risk factors： body mass index （BMI）， hospitalization days， number of smoking years， place of residence， use of noninvasive ventilators， oxygen-demanding therapy， liver cirrhosis， use of systemic glucocorticosteroids， and traditional Chinese medicine syndrome （phlegm and stasis obstructing the lung）. The nomogram model showed good discrimination and calibration in both the training set （AUC=0.748） and validation set （AUC=0.774）. ConclusionThe risk prediction model for frequent acute exacerbations of COPD， integrating traditional Chinese medicine syndrome， constructed in this study has high accuracy. It can provide a scientific basis for early clinical identification of high-risk patients and individualized intervention.

Objective:To explore the feasibility and effectiveness of full free-breathing cardiac magnetic resonance (CMR) in clinical practice.Methods:The study prospectively included patients who underwent full free-breathing CMR and traditional breath-holding cine imaging between June 1 and June 30, 2024. An analysis and comparison were conducted on the image acquisition time, image quality, and left ventricular function parameters under two scanning methods, including left ventricular ejection fraction (LVEF), left ventricular cardiac output (LVCO),left ventricular end diastolic volume (LVEDV), left ventricular end diastolic volume index (LVEDVI), left ventricular end systolic volume (LVESV), left ventricular end systolic volume index (LVESVI), left ventricular stroke volume (LVSV), and left ventricular mass (LVM). In addition, the study conducted both quantitative and qualitative analyses of other sequences in full free-breathing CMR, including T 1 mapping, T 2 mapping, flow imaging, and late gadolinium enhancement (LGE). Group comparisons were performed using the Wilcoxon signed-rank test or paired t-test. Consistency assessments included Bland-Altman analysis, intraclass correlation coefficient ( ICC), and linear regression analysis. Results:Totally, 150 patients were recruited into the study. The average acquisition time of full free-breathing CMR was (22.1±3.1) min, with an average short axis cine sequence examination time of (2.7±0.4) min; The average acquisition time of short axis images in a breath-holding state was (4.9±1.4) min, which was significantly longer than the cine scan in the free-breathing state ( P0.001). The cine and LGE images quality scores obtained from full free-breathing CMR were 4 (4, 4) points and 5 (4, 5) points, respectively, while the cine image quality score obtained in a breath-holding state was 5 (4, 5) points. Compared with traditional breath-hold CMR, free-breathing CMR measurements showed slightly higher LVESV, and LVESVI, while LVEDV, LVEDVI, LVSV, LVCO, LVEF, and LVM were slightly lower, except for LVSV and LVCO, which showed no statistically significant difference, the differences in other cardiac function parameters were statistically significant ( P0.05). However, the two methods demonstrated good consistency( ICC0.947) and correlation (0.808 r0.993, P0.001). The Bland-Altman analysis showed that the bias for all cardiac function parameters was within 8.0%. The Native T 1 and T 2 values for free-breathing CMR were (1 277.5±57.0) ms and 40.1 (38.5, 41.4) ms, respectively, and the results of flow imaging and echocardiography were basically consistent. Conclusions:Free-breathing CMR is feasible and effective in clinical practice, showing a high level of consistency with left ventricular functional parameters obtained from traditional breath-hold scanning. It significantly shortens examination time and holds great clinical value for the promotion and widespread use of CMR.

Background:To compare the efficacy and safety of monthly administrations of gonadotropin releasing hormone (GnRH) agonists LY01005 and Zoladex ? in Chinese patients with premenopausal breast cancer. Methods:From October 2020 to November 2021, 188 premenopausal breast cancer patients were enrolled in 34 hospitals and randomized 1:1 to receive either LY01005 or Zoladex ? every 28 days for a total of three injections. All patients concomitantly received oral tamoxifen (TAM). The primary efficacy endpoint was cumulative probability of maintaining menopausal level [oestradiol (E2) ≤30 pg/ml] from day 29 to day 85. The second efficacy endpoint included changes in E2, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) compared with the baseline. Pharmacokinetics (PK), pharmacodynamics (PD), and safety were analyzed. The study also evaluated the pharmacokinetic and pharmacodynamic characteristics of LY01005. Results:A total of 188 patients were randomised and 187 patients received either LY01005 or Zoladex ?. Cumulative probabilities of maintaining menopausal level (E2≤30 pg/ml) from day 29 to day 85 were 93.1% for LY01005 and 86.3% for Zoladex ?. The between-group difference was 6.8% (95% CI: -2.3%, 15.9%) and primary efficacy in the LY01005 group was not inferior to that in the Zoladex ? group. Changes in E2, LH, and FSH levels compared with the baseline were equivalent between the two groups (E2: 89.34% to 90.23% vs. 82.11% to 85.02%; LH: 88.89% to 95.52% vs. 89.70% to 97.02%; FSH: 75.36% to 80.85% vs.73.07% to 80.24%, respectively). After three consecutive doses of LY01005, the LH and FSH levels of the subjects showed a transient increase after the first dose, reached a peak on the second day and then started to decrease. The LH and FSH reached a lower level and remained at or below that level until the 85th day. Both treatments were well-tolerated. Conclusion:LY01005 is as effective as Zoladex ? in suppressing E2 to menopausal levels in Chinese patients with premenopausal breast cancer, with a similar safety profile.

Objective:To analyze the influencing factors of low fall alertness in elderly inpatients,construct a risk prediction model and validate it,providing a reference for clinical medical staff to identify elderly inpatients with low fall alertness in the early stage.Methods:A total of 605 elderly inpatients treated in Yijishan Hospital affiliated to Wannan Medical College from Oct 2023 to Mar 2024 were enrolled and randomly divided into the training group(n=423)and validation group(n=182)at a ratio of 7∶3.The patients were evaluated using a general information questionnaire,the Social Frailty Screening Tool(HALFT),the Tilburg Frailty Indicator(TFI),and the Self-Awareness of Falls in Elderly scale(SAFE).Multivariate logistic analysis was used to determine the influencing factors of low fall alertness in elderly inpatients.RStudio was used to construct a risk prediction model of low fall alertness.The discrimination,calibration,and clinical net benefit of the model were verified using the receiver operating characteristic(ROC)curves,calibration plots,and decision curve analysis(DCA).Results:Multivariate logistic analysis showed that the history of falls,monthly income,previous physical activity time,social frailty score and TFI score were independent risk factors for low fall alertness in elderly inpatients.The Hosmer-Lemeshow χ2 test showed that χ2=8.863,P=0.354,indicating good calibration of the prediction model.The area under the ROC curve of the training group and the validation group were 0.860(95%CI:0.815-0.904)and 0.937(95%CI:0.888-0.986),respectively,and the maximum Youden indices of the model was 0.576 and 0.788,respectively,indicating good discrimination of the model.The DCA decision curve showed that the model had good clinical effectiveness.Conclusion:The constructed model has a good prediction effect and can help clinical medical staff quickly and effectively screen out elderly inpatients at risk of low fall alertness.

Objective Through in vitro experiments,biomechanical data of the transtibial pullout suture(TPS),tendon reconstruction(TR),and tendon reconstruction with suture augmentation(TRS)were collected,so as to evaluate the biomechanical effectiveness of tendon reconstruction for repairing medial meniscus posterior root tear(MMPRT).Methods Eighteen porcine knee joint models were divided into TPS,TR,and TRS groups.Sutures were used to fix the meniscal root in TPS group.Tendons were passed through an incision at the meniscal root in TR group.Tendons were passed through an incision at the meniscal root and secured at tendon-meniscus contact area with additional sutures in TRS group.The sutures and tendons were pulled out through tibial tunnels and fixed at the anteromedial tibia.All groups underwent failure load tests,and ultimate failure load,displacement at failure load,load at clinical failure,stiffness,and failure modes of the samples were recorded.Results The maximum failure load in TPS group was significantly higher than that in TR group(P＜0.05),but there was no significant difference between TPS group and TRS group(P＞0.05).The maximum failure load in TRS group was significantly higher than that in TR group(P＜0.05).The displacement under failure load in TR group and TRS group was significantly lower than that in TPS group(P＜0.05),but there was no significant difference between TR group and TRS group(P＞0.05).There were no significant differences in the load under clinical failure among the 3 groups(P＞0.05).The stiffness of TRS group was significantly greater than that of TPS group(P＜0.05),but no significant difference was observed between TR group and TPS group,as well as between TR group and TRS group(P＞0.05).All failures were caused by suture or tendon cutting through the meniscus.Conclusions The tendon reconstruction techniques is superior to the TPS in terms of failure displacement and stiffness,while the TRS further enhances the stability of the repair.

Objective To explore the clinical efficacy of the medicated stick massage at meridian knot points in treating Qi stagnation and blood stasis type lumbar disc herniation(LDH)based on the meridian theory.Methods The patients with LDH in the ward 5 of orthopedics department in this hospital from Sep-tember 2024 to April 2025 were selected as the research subjects.On the basis of routine treatment and care,the control group adopted the medicated stick massage at points,while the experimental group adopted the medicated stick massage at meridian knots.The visual analogue scale(VAS)scores,Japanese Orthopaedic So-ciety(JOA)score,TCM syndrome scores and TCM syndrome therapeutic effects before intervention and in two weeks after intervention were compared between the two groups.Results The VAS scores,each item score and total score of JOA,TCM syndrome scores and TCM therapeutic effects after 2-week intervention in the experimental group all were superior to those in the control group,and the differences were statistically significant(P＜0.05).Conclusion Selecting the medicated stick massage at the meridian knots under the guidance of meridian theory could significantly improve the pain symptoms,lumbar function,TCM syndrome scores,the therapeutic effects are definite,and is worthy of clinical promotion and application.

Objective:To evaluate the role of the TANK-binding kinase 1 (TBK1)/receptor-interacting protein kinase 1 (RIPK1) signaling pathway in postoperative cognitive dysfunction (POCD) in aged mice.Methods:Fifty SPF healthy male C57BL/6 mice, aged 18 months, weighing 20-25 g, were divided into 5 groups ( n=10 each) using a table of random numbers: control group (group C), POCD group, dimethyl sulfoxide group, GSK group and GSK+ Nec-1 group. A mouse model of POCD was established by the closed reduction internal fixation of the left tibial fracture in anesthetized animals. Dimethyl sulfoxide, TBK1 inhibitor GSK8612 and RIPK1 inhibitor Nec-1 (0.5 μl/side) were stereotactically injected into the hippocampal CA1 region at 30 min before operation. Cognitive function was assessed using the contextual fear conditioning test before operation and at 3 days after operation. The mice were then anesthetized and sacrificed, and the hippocampal tissues were obtained for determination of the expression of TBK1, RIPK1, interleukin-lbeta (IL-1β), tumor necrosis factor-alpha (TNF-α), activator protein 1 (AP-1) and Nestin (by Western blot), the expression of Bcl-2, Bax and caspase-3 mRNA (by fluorescent quantitative real-time polymerase chain reaction) and for examination of TBK1/RIPK1 molecular interactions and neural stem cell proliferation in the hippocampal dentate gyrus (DG) region (by immunofluorescent staining). Results:Compared with C group, the percentage of freezing time was significantly decreased at 3 days after operation, the expression of Bax mRNA, caspase-3 mRNA, RIPK1, IL-1β, TNF-α and AP-1 was up-regulated, the expression of TBK1, Bcl-2 mRNA and Nestin was down-regulated, and the proliferation of neural stem cells in the hippocampal DG region was decreased in POCD group ( P<0.05 or 0.01). Compared with POCD group, the percentage of freezing time was significantly decreased at 3 days after operation, the expression of Bax mRNA, caspase-3 mRNA, IL-1β, TNF-α and AP-1 was up-regulated, the expression of TBK1, Bcl-2 mRNA and Nestin was down-regulated, and the proliferation of neural stem cells in the hippocampal DG region was decreased in GSK group ( P<0.05 or 0.01). Compared with GSK group, the percentage of freezing time was significantly increased at 3 days after operation, the expression of Bax mRNA, caspase-3 mRNA, IL-1β, TNF-α and AP-1 was down-regulated, the expression of TBK1, Bcl-2 mRNA and Nestin was up-regulated, and the proliferation of neural stem cells in the hippocampal DG region was increased in GSK+ Nec-1 group ( P<0.05 or 0.01). Conclusions:The TBK1/RIPK1 signaling pathway is involved in the pathogenesis of POCD in aged mice.

Objective:To analyze the evolution of ceftazidime/avibactam (CZA) resistance phenotyes and clinical features of 11 ST11-KL64 carbapenem-resistant Klebsiella pneumoniae (CRKP) isolates carrying bla KPC. Methods:Eleven CRKP isolates, designated K01 to K11, obtained from infected liver transplant patients from June to September 2024 were retrospectively studied. Broth microdilution method, whole genome sequencing (WGS) and plasmid conjugation assays were employed to investigate the antimicrobial susceptibility, resistance mechanisms, and genetic structural characteristics of these CRKP isolates. Clinical data were simultaneously collected and organized to analyze the correlation between bla KPC gene mutations and the clinical efficacy of antimicrobial therapy. Results:All eleven isolates of CRKP exhibited multidrug resistance phenotypes. Among them, K01-K09 and K11 were sensitive to CZA and resistant to carbapenems, while K10 was resistant to CZA and displayed sensitivity or intermediate resistance to carbapenems. WGS analysis showed that all 11 CRKP isolates belonged to the ST11-KL64 clonal type. Among these isolates, the K01-K09 and K11 isolates carry the bla KPC-2 gene, whereas the K10 isolate carries the bla KPC-33 gene. A single nucleotide mutation in bla KPC-2 (G532T) resulted in a substitution of tyrosine (Y) for aspartic acid (D) at Ambler position 179 (D179Y), causing resistance of CRKP to CZA and reduced sensitivity to Imipenem and Meropenem. The conjugative plasmid was successfully constructed, and compared to the parental strain, its minimum inhibitory concentration (MIC) to CZA increased 32 folds. Clinical data revealed that the patient developed the bla KPC-33 mutation after 51 days of CZA treatment. Conclusions:The bla KPC-33 mutation following CZA treatment for CRKP infection exhibits a considerable delay. It is essential to dynamically monitor the evolution of CRKP resistance to ensure timely adjustment of therapeutic strategies in case of the occurrence of mutations such as bla KPC-33.

Objective:To compare the efficacy of cannulated screw internal fixation combined with quadratus femoris bone flap with preservation of the posterior superior retinaculum and cannulated screw internal fixation alone in the treatment of femoral neck fracture in young and middle-aged patients.Methods:A retrospective cohort study was conducted to analyze the clinical data of 83 young and middle-aged patients with femoral neck fracture admitted to the 920th Hospital of Joint Logistic Support Force of PLA from January 2018 to January 2023, including 56 males and 27 females, aged 28-55 years [(42.7±3.2)years]. According to Garden classification, the fractures were classified as type III in 22 patients and type IV in 61. Based on Pauwels classification, the fractures were classified as type I in 15 patients, type II in 38 and type III in 30. Forty patients were treated with cannulated screw internal fixation combined with modified quadratus femoris bone flap (cannulated screw combined with bone flap group) and 43 with cannulated screw internal fixation alone (cannulated screw group). The two groups were compared in terms of the operation time, intraoperative blood loss, time to weight-bearing, length of hospital stay, and wound healing. The visual analogue scale (VAS) scores and Harris hip function scores at 1, 3, 6, 12 months after surgery and at the last follow-up. The postoperative complication rate was detected.Results:All the patients were followed up for 20-70 months [(40.0±1.2)months]. The operation time and intraoperative blood loss were (105.2±2.7)minutes and (100.6±16.3)ml in the cannulated screw combined with bone flap group, which were longer or more than (92.4±4.7)minutes and (92.5±14.6)ml in the cannulated screw group ( P<0.01). The time to weight-bearing was (12.1±1.4)weeks in the cannulated screw combined with bone flap group, shorter than (23.6±1.2)weeks in the cannulated screw group ( P<0.01). There was no statistically significant difference in the length of hospital stay between the two groups (P>0.05). The incisions in both groups were healed by first intention. At 1 month after surgery, no statistically significant difference was observed in VAS scores between the two groups ( P>0.05); at 3, 6, 12 months after surgery and at the last follow-up, the VAS scores were (6.6±0.2)points, (4.5±0.3)points, (3.2±0.5)points, and (2.6±0.4)points in the cannulated screw combined with bone flap group, lower than (7.0±0.1)points, (5.2±0.2)points, (3.9±0.4)points, and (3.3±0.1)points in the cannulated screw group ( P<0.05 or 0.01). At 1 and 3 months after surgery, no statistically significant difference was observed in the Harris hip function scores between the two groups ( P>0.05); at 6, 12 months after surgery and at the last follow-up, the Harris hip function scores were (82.2±1.7)points, (90.0±1.4)points, and (91.6±1.0)points in the cannulated screw combined with bone flap group, higher than (75.2±1.7)points, (83.4±1.9)points, and (85.2±0.7)points in the cannulated screw group ( P<0.01). At the last follow-up, in the cannulated screw combined with bone flap group, the Harris hip function was rated excellent in 32 patients, good in 5, and fair in 3, with an excellent and good rate of 92.5%, while in the cannulated screw group, the Harris hip function was rated excellent in 20 patients, good in 13, and fair in 10, with an excellent and good rate of 76.7% ( P<0.05). The postoperative complication rate was 5.0% (2/40) in the cannulated screw combined with bone flap group, significantly lower than 23.2% (10/43) in the cannulated screw group ( P<0.05). Conclusion:Compared with cannulated screw internal fixation alone, cannulated screw internal fixation combined with quadratus femoris bone flap with preservation of the posterior superior retinaculum has the advantages of earlier weight-bearing, less pain, better recovery of hip joint function, and lower incidence of postoperative complications in the treatment of femoral neck fracture in young and middle-aged patients, despite longer operation time and more intraoperative blood loss.