Driven by the global trend of population aging， the prevalence of neurodegenerative diseases， including Alzheimer’s disease （AD）， Parkinson’s disease （PD）， Huntington’s disease （HD）， and amyotrophic lateral sclerosis （ALS）， has been rising consistently. The pathogenic mechanisms of these disorders are complex， and effective disease-modifying therapies remain an unmet clinical need. Ferroptosis， a regulated cell death modality driven by iron-dependent lipid peroxidation， has been widely implicated in the occurrence and evolution of the aforementioned conditions. Under pathological states， both perturbed iron metabolism and reactive oxygen species （ROS） accumulation can precipitate ferroptosis. Specifically， iron overload exacerbates oxidative injury via the Fenton reaction， disrupts the glutathione （GSH）-based antioxidant defense system， and induces extensive peroxidation of polyunsaturated fatty acids （PUFAs）， ultimately culminating in neuronal damage. Furthermore， ferroptosis interacts synergistically with other pathological hallmarks， such as oxidative stress， neuroinflammation， aberrant protein aggregation， and apoptosis， thereby accelerating disease progression. A synthesis of current evidence indicates that disrupted iron homeostasis， enhanced lipid peroxidation， GSH depletion， and impaired glutathione peroxidase 4 （GPX4） activity constitute the common basis for ferroptosis in these neurodegenerative diseases. Concurrently， ferroptosis also displays certain disease‑specific characteristics by engaging distinct pathogenic proteins and regulatory pathways in each disorder. In this review， we delineate the molecular regulatory framework of ferroptosis， summarize its research progress in AD， PD， HD， and ALS， and highlight both shared mechanisms and divergent regulatory pathways across these diseases， with the goal of informing future investigations into disease pathogenesis and the discovery of novel strategies.

Driven by the global trend of population aging， the prevalence of neurodegenerative diseases， including Alzheimer’s disease （AD）， Parkinson’s disease （PD）， Huntington’s disease （HD）， and amyotrophic lateral sclerosis （ALS）， has been rising consistently. The pathogenic mechanisms of these disorders are complex， and effective disease-modifying therapies remain an unmet clinical need. Ferroptosis， a regulated cell death modality driven by iron-dependent lipid peroxidation， has been widely implicated in the occurrence and evolution of the aforementioned conditions. Under pathological states， both perturbed iron metabolism and reactive oxygen species （ROS） accumulation can precipitate ferroptosis. Specifically， iron overload exacerbates oxidative injury via the Fenton reaction， disrupts the glutathione （GSH）-based antioxidant defense system， and induces extensive peroxidation of polyunsaturated fatty acids （PUFAs）， ultimately culminating in neuronal damage. Furthermore， ferroptosis interacts synergistically with other pathological hallmarks， such as oxidative stress， neuroinflammation， aberrant protein aggregation， and apoptosis， thereby accelerating disease progression. A synthesis of current evidence indicates that disrupted iron homeostasis， enhanced lipid peroxidation， GSH depletion， and impaired glutathione peroxidase 4 （GPX4） activity constitute the common basis for ferroptosis in these neurodegenerative diseases. Concurrently， ferroptosis also displays certain disease‑specific characteristics by engaging distinct pathogenic proteins and regulatory pathways in each disorder. In this review， we delineate the molecular regulatory framework of ferroptosis， summarize its research progress in AD， PD， HD， and ALS， and highlight both shared mechanisms and divergent regulatory pathways across these diseases， with the goal of informing future investigations into disease pathogenesis and the discovery of novel strategies.

Triple-negative breast cancer (TNBC) is a subtype of breast cancer that is challenging to treat and lacks targeted therapeutic drugs in the clinic. Natural active ingredients provide promising opportunities for discovering and developing targeted therapies for TNBC. This study investigated the effects of daurisoline on TNBC and elucidated its potential mechanisms. Using network pharmacology, a correlation was identified between daurisoline, derived from Menispermum dauricum, and breast cancer, particularly involving the Notch signaling pathway. The effects of daurisoline on the proliferation, migration, and apoptosis of MDA-MB-231 and MDA-MB-468 cells were evaluated in vitro. Additionally, the impact of daurisoline on the growth of MDA-MB-231 xenograft tumors in nude mice was assessed through in vivo experiments. Expression levels of Notch signaling pathway-related proteins, including Notch-1, NICD, PSEN-1, Bax, and Bcl-2, were examined using molecular docking and Western blotting to explore the underlying mechanisms of daurisoline’s anti-breast cancer effects. It was revealed that daurisoline could effectively inhibit the proliferation and migration of MDA-MB-231 and MDA-MB-468 cells and promote apoptosis. Furthermore, it significantly reduced the growth of subcutaneous tumors in nude mice. Notably, daurisoline could reduce the hydrolytic activity of γ-secretase by binding to the catalytic core PSEN-1, thereby inhibiting activation of the γ-secretase/Notch axis and contributing to its anti-TNBC effects.This study supported the development of naturally targeted drugs for TNBC and provided insights into the research on dibenzylisoquinoline alkaloids, such as daurisoline.

Objective To investigate predictive factors of malignant risk for follicular thyroid neoplasms(FTN)with a maximum diameter≤4 cm,providing evidence for preoperative diagnosis and individualized treatment for FTN patients.Methods We retrospectively analyzed clinical data of FTN patients with a maximum tumor diameter≤4 cm treated at our hospital between January 2018 and December 2023.Based on postoperative pathological diagnosis,the patients were divided into follicular thyroid carcinoma(FTC)group and follicular thyroid adenoma(FTA)group.Univariate and multivariate logistic regression analyses were performed to explore predictive factors of malignant risk of FTN.Results A total of 870 patients were included,comprising of 745 patients(85.6%)in the FTA group and125 patients(14.4%)in the FTC group.The univariate analysis showed thatage,gender,BMI,comorbidity of Hashimoto's thyroiditis,number and location of nodules,the maximum diameter of nodules,internal structure of nodules,and internal blood flow signals had no significant differences(P>0.05),while nodule echogenicity,margins,halo,taller-than-wide shape,and calcification had significant differences(P<0.05).Multivariate logistic regression analysis revealed that irregular margins(OR=3.061,95%CI:1.653-5.667,P=0.000),uneven thickness of the halo(OR=5.868,95%CI:1.258-27.377,P=0.024),and peripheral rim calcification(OR=4.364,95%CI:1.329-14.333,P=0.015)were predictive factors of malignant risk for FTC.Conclusions Ultrasound features have certain value for evaluating benign or malignant nature of FTN.Careful assessment of nodule margins,halo,and calcification can facilitate early diagnosis and treatment of small FTN.

Objective:To investigate the association between serum 25-hydroxyvitamin D [25(OH)D] levels and 24-h urinary calcium excretion (24-h UCaE) and hypercalciuria in Chinese adults.Methods:This cross-sectional study was conducted from March 2022 to March 2023 in nine cities in China and included 1 239 residents. Demographic characteristics were collected through questionnaires and physical examinations, fasting blood samples were assessed for bone metabolism indicators, and 24-h urine samples were used to determine the 24-h UCaE. Multiple linear regression analysis was used to explore the relationship between serum 25(OH)D and 24-h UCaE and bone metabolism indexes. The relationship between serum 25(OH)D and hypercalciuria was analyzed using a multiple logistic regression model combined with restricted cubic spline modeling.Results:The mean participant age was (47.9±18.1) years, of which 453 (36.6%) were male. The percentages of vitamin D sufficiency, insufficiency, and deficiency were 7.6% (94/1 239), 29.0% (359/1 239), and 63.4% (786/1 239), respectively. The multiple linear regression model showed that after adjusting for the covariates the 24-h UCaE gradually increased with higher levels of 25(OH)D ( P overall <0.001, P nonlinear <0.001). The logistic regression analysis revealed that compared with the vitamin D deficient group, the OR for the prevalence of hypercalciuria in the vitamin D sufficient and vitamin D insufficient groups were 3.290 (95% CI 1.745 to 6.202) and 3.742 (95% CI 2.458 to 5.697), respectively. The results of the restricted cubic spline modeling showed a positive nonlinear relationship between 25(OH)D and the prevalence of hypercalciuria ( P overall <0.001, P nonlinear <0.001). The prevalence of hypercalciuria increased when 25(OH)D was >17.00 μg/L and peaked at 26.71 μg/L, after which there was a decreasing trend in the prevalence of hypercalciuria with increasing 25(OH)D. Conclusion:Associations between serum 25(OH)D levels and urinary calcium excretion and the prevalence of hypercalciuria were observed in the Chinese adult population.

Objective:To investigate the clinical characteristics, prevalent serum groups, and drug sensitivity test results of epidemic cerebrospinal meningitis in children in Shanghai area.Methods:The study was a retrospective case-control study. The children hospitalized for epidemic cerebrospinal meningitis in Children′s Hospital of Fudan University from January 2003 to December 2023 were enrolled. Clinical data were collected, including demographic characteristics, clinical manifestations, pathogen detection results, strain typing, and drug sensitivity test results.Results:A total of 77 children with confirmed epidemic cerebrospinal meningitis were hospitalized, including 50 males (64.94%) and 27 females (35.06%). The age was 24(8, 60) months, with 16 cases (20.78%) aged 0 to five months, nine cases (11.69%) aged six to 11 months, 21 cases (27.27%) aged 12 to 35 months, 16 cases (20.78%) aged three to five years, 13 cases (16.89%) aged six to 11 years, and two cases (2.60%) aged 12 years. The highest number of cases was in spring, with 36 cases (46.75%), followed by winter with 25 cases (32.47%). Thirty-three cases (42.86%) had vaccinated with meningococcal vaccine. The clinical symptoms included fever in all 77 cases (100.00%), skin petechiae and ecchymosis in 58 cases (75.32%), vomiting in 56 cases (72.73%), respiratory symptoms in 12 cases (15.58%), convulsions in 17 cases (22.08%), conscious disturbance in 24 cases (31.17%), shock in 38 cases (49.35%), circulatory failure in 13 cases (16.88%), and respiratory failure in seven cases (9.09%). Among the 77 children, fifty-seven cases (74.03%) were common type and 20 cases (25.97%) were fulminant type, with seven deaths (9.09%). Neisseria meningitidis (Nm) was detected in 55 cases (71.43%), with the positive rates of skin petechiae smear and cerebrospinal fluid smear of 23.26%(10/43) and 19.44%(14/72), respectively. The positive rates of cerebrospinal fluid culture and blood culture were 36.51%(23/63) and 31.51% (23/73), respectively. The positive rate of polymerase chain reaction detection was 79.17%(38/48). The serogroups were determined in the 38 Nm strains, including 18 cases (47.37%) of group B, 14 cases (36.84%) of group C, five cases (13.16%) of group A, and one case (2.63%) of group Y. Among the 29 Nm strains tested for antimicrobial susceptibility, one strain (3.45%) was resistant to penicillin, two strains (6.90%) were resistant to cefotaxime, 21 strains (72.41%) were resistant to ciprofloxacin, and 25 strains (86.21%) were resistant to sulfamethoxazole/trimethoprim. All strains were sensitive to ceftriaxone, azithromycin, meropenem, rifampicin, chloramphenicol, and minocycline. Conclusions:Epidemic cerebrospinal meningitis presents a low prevalence trend in children in Shanghai area. Infants and toddlers remain the major susceptible individuals. Nm has reduced sensitivity to penicillin, but remains sensitive to ceftriaxone. Ceftriaxone is recommended as the first-line choice for antibiotic therapy. The prevalent serogroups are Group B, Group C, Group A and Group Y in sequence. Immunization plan adjustment should be suggested. Vaccination covering the current epidemic serum population as early as possible should be recommended.

AIM To investigate the effects of Changpu Yujin Decoction(CPYJD)on striatal mitophagy and PINK1/Parkin signaling pathway in a rat model of Tourette syndrome(TS).METHODS Thirty-six SPF male SD rats were randomly assigned to the control group(n=9)and the TS modeling group(n=27).Rats in the modeling group received daily intraperitoneal injections of 3,3'-iminodipropionitrile(IDPN)(300 mg/kg)for 7 consecutive days to establish the TS model.Post-modeling,successfully induced TS rats were re-randomized into model group(no treatment),tiapride group(47.91 mg/kg)and CPYJD group(77.28 g/kg).All groups received their respective interventions via intragastric administration daily for 28 days.Following drug administration,behavioral scores were assessed in each group.Pathological alterations in the striatum were examined using HE staining,while ultrastructural changes were evaluated by transmission electron microscopy(TEM).Neuronal apoptosis was quantified via TUNEL staining,and ROS levels in striatum were measured by ELISA.Co-localization of PINK1 and LC3B was assessed using immunofluorescence(IF).Finally,mRNA and protein expressions of PINK1,Parkin,Beclin-1,P62 and LC3B(LC3B-Ⅱ/Ⅰ ratio)were analyzed by RT-qPCR and Western blot.RESULTS Compared to the control group,the model group demonstrated significantly increased behavioral scores(P＜0.01),elevated neuronal apoptosis rate and higher ROS levels in the striatum(P＜0.01);severe neuronal and mitochondrial damage in the striatum;significantly reduced mRNA and protein expressions of PINK1,Parkin,Beclin-1 and LC3B(LC3B-Ⅱ/Ⅰ ratio)in the striatum(P＜0.01);markedly upregulated P62 mRNA and protein expressions(P＜0.01).Compared to the model group,both the tiapride and CPYJD intervention groups exhibited significantly reduced behavioral scores(P＜0.01);decreased neuronal apoptosis rate and lower ROS levels(P＜0.01);improved pathological alterations in the striatal neurons and mitochondria;increased mRNA and protein expressions of PINK1,Parkin and Beclin-1 in the striatum(P＜0.05,P＜0.01);and decreased P62 mRNA and protein expressions(P＜0.01).Furthermore,the rats in the CPYJD group specifically showed elevated LC3B mRNA level and LC3B-Ⅱ/Ⅰ protein ratio in striatum(P＜0.05,P＜0.01).CONCLUSION The effect of CPYJD intervention in TS rats may involve activation of mitophagy through regulation of the PINK1/Parkin signaling pathway,improving mitochondrial function,reducing ROS levels,and thereby protecting neurons.

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.

Poly(lactic-co-glycolide)(PLGA)is a key excipient in long-acting sustained-release preparations,and its degradation properties directly affect the drug release behavior.In this study,PLGA microspheres were prepared by microfluidic techniques,and the morphology changes of the microspheres were observed by scanning electron microscopy(SEM).In alkaline environment,due to the accelerated hydrolysis of ester bonds,the surface of the microspheres was rapidly dissolved and eroded,and the degradation rate was significantly higher than that in acidic environment.High temperature accelerated the degradation of PLGA microspheres.Under neutral and alkaline conditions,the microspheres showed aggregation and adhesion.Under acidic conditions,the microspheres gradually decomposed into irregular fragments.The high ionic strength further promoted the surface corrosion of the microspheres,especially under extreme pH conditions.Simultaneously,PLGA microspheres encapsulating coumarin were prepared to simulate the microsphere formulation.The release rate of coumarin after degradation of the microspheres under different conditions was observed by measuring the absorbance with ultraviolet-visible spectrophotometry.The results were consistent with those of the blank microspheres.This study revealed that the degradation of PLGA microspheres was significantly pH-dependent,temperature sensitive and ion strength responsive.These findings not only helped to understand and optimize the long-term stability and controlled release performance of drug-carrying microspheres,but also provided a theoretical basis for further improvement of PLGA-based drug carrier design.

6-Thioguanine(6-TG)is an antineoplastic agent used in treatment of acute leukemia.However,significant interindividual variability in dosing regimens and frequent clinical manifestations of hepatotoxicity and myelosuppression as adverse effects have affected its therapeutic efficacy.Consequently,the development of rapid analytical methods for 6-TG in clinical samples,enabling continuous therapeutic drug monitoring of plasma concentrations,holds substantial significance in optimizing dosage regimens,mitigating adverse reactions,and investigating drug metabolism mechanisms.In this study,multi-tipped gold nanostars(AuNSs)were prepared.With bis-(p-sulfonylphenyl)phenylphosphine molecule as the protecting agent and internal standard molecule,the AuNSs were assembled onto a highly sensitive surface-enhanced Raman(SERS)substrate for developing a ratio-based SERS quantitative analysis method for 6-TG in serum.The AuNSs containing multiple tips and gaps exhibited strong local surface plasmon resonance effect and SERS activity,ensuring the sensitivity of the analytical method.Furthermore,the introduction of internal standard molecules could improve the reproducibility,which guaranteed this method suitable for rapid analysis of drug molecules in complex samples.Quantitative analysis of 6-TG was achieved with linear detetion range of 1.0×10?4-1.0 mmol/L.In the spiked recovery experiments of serum,the RSD was less than 5.32%,and the recoveries were 94%-104%,which proved that this method could be used for rapid quantitative determination of 6-TG in serum.This method provided a powerful tool for studying drug pharmacokinetics,which could promote the optimization of the usage methods of anti-cancer drugs,and it was expected to further enhance the clinical efficacy and safety of 6-TG,enabling it to achieve the best therapeutic effect.