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.

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 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.

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.

A method was developed for determination of dilauryl thiodipropionate(DLTDP)in fried foods by coupling solid-phase extraction(SPE)pretreatment with reverse-phase liquid chromatography-tandem mass spectrometry(RPLC-MS/MS)detection.Samples were extracted with n-hexane as the solvent,purified using a neutral alumina SPE cartridge,and finally analyzed by RPLC-MS/MS.Quantitative analysis was performed using matrix-matched calibration curves combined with an external standard method under optimal experimental conditions.The results showed that DLTDP exhibited good linearity in the range of 2.0-50.0 μg/L,with a correlation coefficient(R2)≥0.999.The limit of detection(LOD)and the limit of quantification(LOQ)of the method were 0.15 mg/kg and 0.5 mg/kg,respectively.The mean recoveries at three fortification levels(0.5,1.0,and 200 mg/kg)in different samples ranged from 84.8%to 96.8%,with the relative standard deviations(RSDs)all less than 8.0%.The developed method was highly sensitive,accurate and reliable,and easy to operate,making it well suited for the routine quantitative analysis of DLTDP in fried foods.

Objective To establish a rapid screening and analysis method for etomidate and its ana-logues using a portable mass spectrometer equipped with a thermal desorption-atmospheric pressure chemical ionization source-linear ion trap.Methods A 10 μL aliquot of a standard solution at a con-centration of 1 μg/mL was taken,and after the solvent evaporated,the sample was inserted into the in-let of the portable mass spectrometer for detection.By adjusting the collision-induced dissociation pa-rameters,the molecular ion peak and fragment ion peak information of the standard were obtained and used to establish a reference database.In addition,the method was applied to 29 seized liquid and plant samples.Results A screening system for etomidate and its analogues was established based on the portable mass spectrometer and the corresponding mass spectrometry library.The system enables qualitative screening analysis by identifying primary protonated molecular ions and secondary product ions of etomidate and its analogues.The limits of detection for etomidate and its 12 analogues ranged from 0.1 to 10 μg/mL.Etomidate and its analogues were detected in all 29 liquid and plant samples.However,this method could not distinguish between isomeric imidazole esters,such as isopropoxate and propoxate.Additionally,when testing 2-SH-etomidate,there was a false positive for the detection of etomidate.Conclusion This study established a rapid screening method for etomidate and its ana-logues using a portable mass spectrometer.The method combines the high sensitivity of mass spectrome-try with the on-site applicability of portable devices,significantly improving detection efficiency and meeting the on-site detection needs of etomidate and its analogues.

OBJECTIVE: To elucidate the specific mechanisms by which electroacupuncture (EA) alleviates anxiety and fear behaviors associated with posttraumatic stress disorder (PTSD), focusing on the role of lipocalin-2 (Lcn2). METHODS: The PTSD mouse model was subjected to single prolonged stress and shock (SPS&S), and the animals received 15 min sessions of EA at Shenmen acupoint (HT7). Behavioral tests were used to investigate the effects of EA at HT7 on anxiety and fear. Western blotting and enzyme-linked immunosorbent assay were used to quantify Lcn2 and inflammatory cytokine levels in the prefrontal cortex (PFC). Additionally, the activity of PFC neurons was evaluated by immunofluorescence and in vivo electrophysiology. RESULTS: Mice subjected to SPS&S presented increased anxiety- and fear-like behaviors. Lcn2 expression in the PFC was significantly upregulated following SPS&S, leading to increased expression of the proinflammatory cytokines tumor necrosis factor-α and interleukin-6 and suppression of PFC neuronal activity. However, EA at HT7 inhibited Lcn2 release, reducing neuroinflammation and hypoexcitability in the PFC. Lcn2 overexpression mitigated the effects of EA at HT7, resulting in anxiety- and fear-like behaviors. CONCLUSION EA at HT7 can ameliorate PTSD-associated anxiety and fear, and its mechanism of action appears to involve the inhibition of Lcn2-mediated neural activity and inflammation in the PFC. Please cite this article as: Yang YD, Zhong W, Chen M, Tang QC, Li Y, Yao LL, et al. Electroacupuncture alleviates behaviors associated with posttraumatic stress disorder by modulating lipocalin-2-mediated neuroinflammation and neuronal activity in the prefrontal cortex. J Integr Med. 2025; 23(5):537-547.
Electroacupuncture ; Stress Disorders, Post-Traumatic/metabolism* ; Animals ; Lipocalin-2/metabolism* ; Prefrontal Cortex/physiopathology* ; Male ; Mice ; Neurons/physiology* ; Disease Models, Animal ; Fear ; Behavior, Animal ; Mice, Inbred C57BL ; Neuroinflammatory Diseases/metabolism* ; Anxiety/therapy* ; Acupuncture Points

OBJECTIVE: Recent studies have overturned the traditional concept of the lung as a "sterile organ" revealing that pulmonary microbiota dysbiosis and abnormal surfactant proteins (SPs) expression are involved in the progression of silicosis. This study aimed to investigate the relationship between abnormal SPs expression and dysbiosis of lung microbiota in silica-induced lung fibrosis, providing insights into mechanisms of silicosis. METHODS: Lung pathology, SPs expression, and microbiota composition were evaluated in silica-exposed mice. A mouse model of antibiotic-induced microbiota depletion was established, and alveolar structure and SPs expression were assessed. The roles of the lung microbiota and SPs in silicosis progression were further evaluated in mice with antibiotic-induced microbiota depletion, both with and without silica exposure. RESULTS: Silica exposure induced lung inflammation and fibrosis, along with increased expression of SP-A expression. Antibiotics (Abx)-induced microbiota depletion elevated SP-A and SP-D expression. Furthermore, silica exposure altered lung microbiota composition, enriching potentially pathogenic taxa. However, antibiotic-induced microbiota depletion prior to silica exposure reduced silica-mediated lung fibrosis and inflammation. CONCLUSION Lung microbiota is associated with silica-induced lung injury. Overproduction of SP-A and SP-D, induced by Abx-induced microbiota depletion, may enhance the resistance of mouse lung tissue to silica-induced injury.
Animals ; Silicosis/prevention & control* ; Lung/metabolism* ; Mice ; Anti-Bacterial Agents/pharmacology* ; Microbiota/drug effects* ; Silicon Dioxide/toxicity* ; Mice, Inbred C57BL ; Male ; Pulmonary Surfactant-Associated Proteins/genetics*