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 explore the clinical efficacy and mechanism of Bupi Qingfei prescription （BPQF） in treating stable bronchiectasis in the patients with syndromes of lung-spleen Qi deficiency and phlegm-heat accumulation in the lungs. MethodsA randomized， double-blind， placebo-controlled trial was conducted. Patients were randomized into BPQF and placebo control （PC） groups. On the basis of conventional Western medicine treatment， the BPQF granules and placebo were respectively administered at 10 g each time， twice a day， for a course of 24 weeks. The TCM symptom scores， Quality of Life Questionnaire for Bronchiectasis （QOL-B） scores， lung function indicators， T lymphocyte subsets， level of inflammatory factors in the sputum， level of neutrophil elastase （NE） in the sputum， and occurrence of adverse reactions were observed before and after treatment in the two groups. ResultsA total of 64 patients completed the study， encompassing 32 in the BPQF group and 32 in the PC group. After treatment， the BPQF group showed decreased TCM symptom scores （P<0.01）， increased QOL-B scores （P<0.01）， and declined levels of tumor necrosis factor （TNF）-α and NE （P<0.05， P<0.01）. The PC group showed decreased TCM symptom （except spleen deficiency） scores （P<0.01）， increased the QOL-B health cognition and respiratory symptom domain scores （P<0.05， P<0.01）， and a declined TNF-α level （P<0.01）. Moreover， the BPQF group had lower TCM symptom （except chest tightness） scores （P<0.05， P<0.01）， higher QOL-B （except treatment burden） scores （P<0.05， P<0.01）， and lower levels of interleukin-6 and TNF-α （P<0.05） than the PC group. Neither group showed serious adverse reactions during the treatment process. ConclusionBPQF can ameliorate the clinical symptoms of stable bronchiectasis patients who have lung-spleen Qi deficiency or phlegm-heat accumulation in the lungs by regulating the immune balance and inhibiting airway inflammatory responses.

Objective To compare the efficacy and safety of transurethral blue laser vaporization of the prostate, transurethral resection of the prostate (TURP) or plasmakinetic resection of the prostate in the treatment of benign prostatic hyperplasia (BPH). Methods The domestic and foreign clinical studies on transurethral blue laser vaporization of the prostate (observation group), TURP or plasmakinetic resection of the prostate (control group) in the treatment of BPH during Jan. 2015 and Mar. 2025 were retrieved. The data were extracted with Cochrane systematic review method. The operation time, decrease in hemoglobin, bladder irrigation time, catheter indwelling time, total complication rate, retrograde ejaculation rate and urinary incontinence rate of the two groups were compared with RevMan 5.3.0 statistical software. Results A total of 5 Chinese studies involving 491 patients (248 in the observation group and 243 in the control group) were included in the Meta-analysis. Compared with the control group, the observation group had shorter operation time [MD=-20.80, 95%CI:-26.88—-14.72, P＜0.00001], less decrease in hemoglobin [MD=-10.61, 95%CI: -20.21—-1.01, P=0.03], shorter bladder irrigation time [MD=-17.85, 95%CI: -32.62—-3.09, P=0.002], shorter catheter indwelling time [MD=-1.71, 95%CI: -2.81—- 0.62, P=0.002], lower total complication rate [OR=0.11, 95%CI: 0.06—0.21, P＜0.00001], lower retrograde ejaculation rate [OR=0.05, 95%CI: 0.02—0.16, P＜0.00001] and lower urinary incontinence rate [OR=0.24, 95%CI: 0.07—0.79, P=0.02]. There were no significant differences in other complications between the two groups (P＞0.05). The international erectile function score (IIEF-5) of the observation group was significantly higher than that of the control group [MD=1.87, 95%CI:1.16—2.57, P＜0.00001]. There were no significant differences in international prostate symptom score (IPSS), maximum urinary flow rate (Qmax) and post-voiding residual (PVR) between the two groups (P＞0.05). Conclusion All three surgical procedures can effectively improve the lower urinary tract symptoms of BPH patients. Compared with TURP or plasmakinetic resection of the prostate, transurethral blue laser vaporization of the prostate has obvious advantages in terms of perioperative recovery, reduction of total complications, urinary incontinence and retrograde ejaculation rates, and preservation of sexual function.

Objective The study aimed to elucidate the population composition and seasonal distribution characteristics of mosquitoes in Laoshan District, Qingdao City, providing a scientific basis for the prevention and control of mosquito-borne infectious diseases. Methods Mosquito surveillance was conducted in Laoshan District in Qingdao City using light traps from April to November 2020-2022. Dominant mosquito species were identified using the Berger-Parker dominance index(I)and mosquito density was compared using the Kruskal-Wallis H test. The seasonal distribution characteristics of adult mosquitoes were analyzed using concentration and circular distribution method. Spearman rank correlation analysis was used to study the relationship between mosquito populations and meteorological factors with mean monthly temperature, mean monthly relative humidity, and mean monthly rainfall. Results The mean mosquito density for the trapping period was 9.771 females/(trap·night)in 2020,9.771 in 2021, and 9.427 in 2022. There was no statistically significant difference in mosquito density between different years(H = 0.095, P = 0.954). In total, 2 781 adult female mosquitoes comprising five species from four genera were captured over three years. Culex pipiens(I = 0.654), Aedes albopictus(I = 0.202), and Aedes aegypti(I = 0.118)were identified as dominant species. Seasonal fluctuations in the adult mosquitoes were unimodal, and primarily concentrated from June to September. The peak period of adult mosquito varied between years with statistical significance. (F = 3.838, P ＜ 0.05). Mosquito density was highly correlated with mean monthly temperature, mean monthly relative humidity and mean monthly precipitation(P＜ 0.05). Conclusions Cx. pipiens pallens, Ae. albopictus, and Ar. inamoratus are the dominant mosquito species in the Laoshan District of Qingdao City. The activity of adult mosquitoes is seasonal, and primarily concentrated in summer and autumn, during which the risk of mosquito-borne diseases such as dengue fever is increased.

Background: and Purpose Limited evidence exists on the effectiveness of endovascular treatment (EVT) for acute posterior circulation tandem lesion (PCTL). This study aimed to explore the role of extracranial vertebral artery (VA) stenting in patients with PCTL stroke undergoing EVT. Methods: Individual patient data were pooled from the BASILAR (EVT for Acute Basilar Artery Occlusion Study) and PERSIST (Posterior Circulation Ischemic Stroke) registries. Patients with PCTLs who underwent EVT were included in the present cohort and divided into the stenting and nonstenting groups based on the placement of extracranial VA stents. The primary efficacy outcome was the modified Rankin Scale (mRS) scores at 90 days and 1 year. Safety outcomes included 24-hour symptomatic intracranial hemorrhage (sICH) and all-cause mortality at 90 days and 1 year post-surgery. Results: A combined dataset of 1,320 patients with posterior circulation artery occlusion, including 263 (19.9%) with tandem lesions, of whom 217 (median age, 65 years; 82.9% male) met the inclusion criteria for the analysis. The stenting group had 84 (38.7%) patients, while the non-stenting group had 133 (61.3%). After adjustment for the potential confounders, extracranial VA stenting was associated with favorable shifts in mRS scores at both 90 days (adjusted common odds ratio [OR], 2.30; 95% confidence interval [CI], 1.23–4.28; P<0.01) and 1 year (adjusted OR [aOR], 2.04; 95% CI [1.05–3.97]; P=0.04), along with lower rate of mortality at both 90 days (aOR, 0.45; 95% CI [0.21–0.93]; P=0.01) and 1 year (aOR, 0.36; 95% CI [0.16–0.79]; P=0.01), with no significant difference in sICH incidence (aOR, 0.35; 95% CI [0.06–1.98]; P=0.24). Conclusion Extracranial VA stenting during EVT may improve functional outcomes and reduce mortality in patients with PCTL strokes.

In this study, RAW264.7 cells were employed to investigate the effects of honey-processed Astragalus on their energy metabolism and polarization, and explore the scientific connotation of the enhanced efficacy of honey-processed Astragalus on invigorating spleen-stomach and replenishing Qi. The medicated sera were prepared by intragastric administration of rats with water extracts of crude and honey-processed Astragalus, and the composition changes of medicated sera of crude and honey-processed Astragalus were analyzed by using LC-MS technology. The cell survival rates were detected and the concentrations of medicated sera were screened through CCK-8 assay. The differences of cell phagocytic rates, ATP energy metabolism, and NO secretion between crude and honey-processed Astragalus were evaluated by using neutral red phagocytosis assay, ATP detection kit, and NO detection kit. The effects of crude and honey-processed Astragalus on TNF-α secretion of RAW264.7 cells were detected by employing ELISA kit. The effects of crude and honey-processed Astragalus on polarization of RAW264.7 cells were evaluated by utilizing flow cytometry. The differential metabolites related to glycolysis in cell lysates and culture media were screened by using LC-MS technology. The experiment was approved by the experimental animal ethics committee from Shanxi University of Chinese Medicine (No. AWE202407352). The results showed that the contents of betaine, amino acids, and ononin in the prepared medicated sera of rats treated by intragastric administration with water extracts of honey-processed Astragalus increased compared to those in crude one. The results of CCK-8 experiment showed that there were no cytotoxic effects on RAW264.7 cells in the medicated sera of crude and honey-processd Astragalus at different concentration. The phagocytic index and ATP yield both increased to varying degrees after administration of the medicated sera to cells. The secretion of NO in normal and inflammatory cells increased and decreased respectively, and the effect of honey-processed Astragalus was better than that of crude one. The results of ELISA kit showed that the medicated sera of both crude and honey-processed Astragalus could promote the secretion of TNF-α in a concentration-dependent manner, and the promoting effect of honey-processed Astragalus was stronger than that of crude one. The results of flow cytometry showed that the medicated sera of both crude and honey-processed Astragalus could promote M1-type polarization and inhibit M2-type polarization of RAW264.7 cells, and the effect of honey-processed Astragalus was better than that of crude one. Compared to crude Astragalus, the metabolites related to glycolysis in the cell lysates and culture media of the medicated sera of honey-processed Astragalus were generally on the rise, indicating that the effect on promoting glycolysis of honey-processed Astragalus was better than that of crude one. In summary, honey-processed Astragalus can promote the polarization and energy metabolism of RAW264.7 cells, and participate in positive immune regulation, which is correlated with its enhanced effect of invigorating spleen-stomach and replenishing Qi.

Objective:An in vivo mammalian hepatocyte Unscheduled DNA Synthesis(UDS)test was used to evaluate the genotoxicity of Cross-linked Sodium Hyaluronate Gel and Bone Repair Materials,providing experimental evidence for establishing a UDS testing method for medical devices and materials.Methods:0.9％sodium chloride injection and cottonseed oil were used as the solvent for test materials and negative control,respectively.N-dimethylnitrosamine(NDMA)was used as the positive control for the early sampling times,and 2-acetylaminofluorene(2-AAF)was used as the positive control for the late sampling times.SD rats were administered a single dose for toxic exposure,and liver tissues were collected at 4 h and 16 h,respectively.Hepatocytes were isolated using collagenase perfusion.After labeling with 5-ethynyl-2'-deoxyuridine(EdU),and the net average fluorescence intensity(NAFI)of cell nuclei and nucleoplasm was measured by fluorescence microscope.Data from 50 cells were used to analyze the DNA repair level.Results:Compared with the negative control groups,the positive control groups(NDMA and 2-AAF)showed highly statistically significant differences in NAFI(P＜0.01),indicating successful induction of DNA damage.There was no statistically significant differences between the cross-linked sodium hyaluronate gel groups,bone repair material groups and the negative control group(P＞0.05),suggesting that these materials did not significantly induce DNA damage under the experimental conditions.Conclusion:This study first applied EdU labeling technology to the in vivo hepatic UDS assay,achieving non-radioactive labeling through click chemistry reactions.Under the conditions of this study,cross-linked sodium hyaluronate gel and bone repair materials did not exhibit genotoxicity.In the follow-up,the sample range can be expanded and the observation period can be prolonged to further improve the genotoxicity evaluation system of medical devices.

Aim To investigate the effect of eplerenone(EPL)on the alleviation of rheumatoid arthritis(RA)based on voltage-gated potassium channel 1.3(Kv1.3)/B-cell lymphoma-2(Bcl-2)/nuclear factor-κB(NF-κB)to inhibit macrophage M1 polarization in mice.Methods Bioinformatics technology was used to screen disease pathways and targets,and the binding affinity and stability of EPL-Kv1.3 complex system were calculated.A mouse model of RA was established and treated with EPL by intragastric administration for 42 days.The indicators reflecting drug remission of RA were recorded and detected.RAW264.7 cells were treated with EPL to detect the indicators reflecting the effect of drugs on macrophage M1 polarization,and to verify the upstream and downstream key targets of re-lated signaling pathways mediated by drugs.Results Bioinformatics analysis showed that the disease targets were mainly involved in inflammatory response and NF-κB signaling pathway,and EPL-Kv1.3 had high affinity and stable binding.In animal experiments,the detec-tion of anti-cyclic citrullinated peptide antibody(CCP-Ab)and joint score indicated the successful establish-ment of the model.Compared with the model group,EPL could reduce the toe redness and swelling score,alleviate the plantar redness and swelling,synovial swelling,and reduce fibrosis and inflammatory cell in-filtration in mice.The medium-dose and high-dose EPL groups reduced the HE staining score(P＜0.05,P＜0.01),and the high-dose EPL group reduced the serum RF in mice(P＜0.01).CCK-8 results showed that low,medium and high doses of EPL had no effect on the activity of RAW264.7 macrophages(P＞0.05).Compared with the model group,EPL treatment significantly reduced the contents of IL-6,TNF-α and NO in supernatant of the cells(P＜0.01),reduced the nuclear translocation of NF-KB-p65 in the high-dose EPL group,reduced the M1 polarization and increased the proportion of M2 polarization in the medium and high-dose EPL groups(P＜0.01).The mRNA levels of MyD88,IκB-α,NF-κB-p65,NF-KB-p50,IL-1 β and iNOS were significantly reduced in each dose group of EPL(P＜0.01).EPL significantly increased the pro-tein expression of Bcl-2(P＜0.01)and decreased the protein expression of Kv1.3,MyD88,p-IκB-α/IκB-α,p-p65/p65,IL-1 β and iNOS(P＜0.05).Conclusion EPL may play an immunomodulatory role in relieving RA in mice by regulating Kv1.3/Bcl-2/NF-κB path-way,reducing macrophage M1 polarization and amelio-rating macrophage-associated inflammatory response.

Aging is the result of the accumulation of various molecular and cellular damages over time,encompassing 12 characteristic hallmarks divided into three categories.These include primary hallmarks such as genomic instability,telomere attrition,epigenetic alterations,loss of proteostasis,and disabled macroautophagy;antagonistic hallmarks like deregulated nutrient sensing,mitochondrial dysfunction,and cellular senescence;and integrative hallmarks including stem cell exhaustion,altered intercellular com-munication,chronic inflammation and dysbiosis.Therefore,investigating cellular signaling factors within a single pathway is insufficient to comprehensively understand the complex mechanisms underlying aging.Casein kinase Ⅱ(CK2),one of the earliest identified protein kinases,is capable of phosphorylating ser-ine/threonine/tyrosine residues on hundreds of substrates.It exhibits highly constitutive expression and activity,and is extensively involved in the regulation of cellular processes such as proliferation,differenti-ation,apoptosis,stress response,metabolism,and immune function.CK2 plays a unique role in coordi-nating the cross-talk and integration of various signaling pathways,which is crucial for maintaining cell survival and homeostasis.Recent studies have revealed that CK2 exhibits perturbations in both expression levels and enzymatic activity during aging process,with notable heterogeneity observed across different animals,tissues and cellular models.Overall,the downregulation of CK2 expression not only promotes the development of primary hallmarks but also alleviates antagonistic hallmarks and ameliorates integrative hallmarks of aging,demonstrating dual effect and interconnected mechanisms.Notably,aberrant activa-tion in CK2 expression and activity are associated with various aging-related diseases,including cancer,cardiovascular diseases,chronic metabolic disorders,neurodegenerative diseases and skeletal degenera-tive conditions.Therefore,maintaining CK2 homeostasis may represent an effective strategy for delaying aging.This review summarizes the latest advances in CK2 and aging research,providing not only deeper insights into the common mechanisms underlying aging and aging-related diseases,but also a theoretical foundation for identifying potential targets for the early prevention of aging-related diseases.

Objective To systematically review and quantitatively analyze the safety of biologic agents for the clinical treatment of psoriasis during pregnancy and lactation.Methods The literature from start of database to June 27,2023,was searched in MEDLINE(PubMed),Embase,Cochrane Library,and Web of Science by two researcher.Quality of included studies was assessed by the quality evaluation tool of case series from Australian JBI Evidence Based Healthcare Centre.According to Preferred Reporting Items for Systematic Reviews and Meta-Analyses(PRISMA),a systematic review and was conducted to assess pregnancy or breastfeeding outcomes in psoriasis patients exposed to biologics within 3 months prior to pregnancy,during pregnancy or breastfeeding.Data on pregnancy and exposure characteristics were pooled,and the prevalence of adverse pregnancy outcome was summarized using a random effects model.Results A total of 54 studies involving 1206 pregnancies in 1177 female patients with psoriasis exposed to biologic agents were included in the analysis.Systematic review results demonstrated that the majority of the exposures were limited to early pregnancy,with pooled spontaneous abortion rates,elective abortion rates,overall mortality,preterm birth rates,incidence of low birth weights,and congenital anomalies similar to those of general population(P>0.05).Furthermore,no serious adverse reactions were reported during lactation.Conclusions The use of biologic agents in pregnant and breastfeeding women with psoriasis does not significantly increase the risk of adverse pregnancy outcomes and does not affect neonatal health or growth.However,the limited available safety data underscores the necessity of further studies to establish the relationship between psoriasis,biologic agents,and pregnancy/lactation outcomes,thereby providing comprehensive guidance for clinical practice.