ObjectiveMultiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS); however, its underlying neurological pathogenic mechanisms remain incompletely understood. Endogenous formaldehyde (FA), a metabolic byproduct of methylation-demethylation cycles, has recently been implicated in neurotoxicity, oxidative damage, and cognitive impairment. This study aimed to investigate whether excessive FA contributes to myelin sheath demyelination in mice and to evaluate the protective effects and mechanisms of two FA-elimination strategies: sodium bisulfite (NaHSO₃), a classical FA scavenger, and polyethylene glycol-modified astaxanthin nanoparticles (PEG-ATX@NPs), a brain-targeted nano-antioxidant formulation. MethodsA chronic demyelination model was established by feeding female C57BL/6J mice a diet containing 0.2% cuprizone (CPZ) for four weeks, followed by a two-week intervention period. Eighty mice were randomly assigned to four groups: NS (normal saline), CPZ+NS, CPZ+NaHSO₃, and CPZ+PEG-ATX@NPs. Behavioral tests, including open-field, Y-maze, and pole-climbing assays, were conducted to assess locomotor activity, motor coordination, and working memory. FA levels in serum, corpus callosum, and spinal cord were measured using an Na-FA fluorescent probe and quantified via in vivo and ex vivo fluorescence imaging. Neuroinflammatory responses were evaluated by measuring TNF-α, IL-1β, and IL-6 levels using ELISA, while oxidative stress was assessed by reactive oxygen species (ROS) fluorescence intensity. Demyelination was examined via Luxol fast blue staining, and microglial activation was analyzed by Iba1 immunofluorescence. Correlation analyses were performed to explore relationships among FA levels, inflammatory cytokines, ROS intensity, and behavioral parameters. ResultsCompared with the NS group, mice in the CPZ+NS group exhibited significant weight loss, impaired motor coordination and memory, and markedly reduced myelin regeneration (P<0.05). FA levels and pro-inflammatory cytokines were significantly elevated in serum, corpus callosum, and spinal cord (P<0.05). FA-associated fluorescence in brain and spinal tissues, as well as ROS intensity across all tissues examined, also increased substantially (P<0.05). CPZ treatment induced pronounced microglial activation and severe demyelination in the corpus callosum (P<0.01). Both NaHSO₃ and PEG-ATX@NPs effectively reduced FA accumulation in the brain and spinal cord, attenuated demyelination, suppressed microglial activation, decreased inflammatory cytokine levels, and improved motor and cognitive performance. These results confirm that CPZ induced severe demyelination accompanied by oxidative stress, neuroinflammation, and abnormal FA accumulation. Following intervention with either NaHSO₃ or PEG-ATX@NPs, endogenous FA levels in the CNS were substantially reduced. Both treatments alleviated demyelination and significantly decreased the number of activated microglia. Levels of TNF-α, IL-1β, and IL-6 in serum, corpus callosum, and spinal cord were downregulated. Behavioral performance improved significantly, as evidenced by enhanced locomotor activity, better coordination, and improved memory function. These findings indicate that both FA-scavenging agents mitigate CPZ-induced biochemical and behavioral abnormalities. ConclusionThis study demonstrates that excessive endogenous FA is closely associated with cognitive impairment, inflammatory dysregulation, and demyelination in a CPZ-induced chronic demyelination mouse model. Clearing abnormally elevated FA effectively reduces neuroinflammation, suppresses microglial overactivation, decreases oxidative stress, and alleviates demyelination, ultimately improving motor and cognitive outcomes in mice. These results suggest that targeting endogenous FA represents a promising therapeutic strategy for MS and other demyelinating disorders. Further investigations are warranted to explore the long-term safety, dosage optimization, and molecular pathways involved in FA-mediated neurotoxicity.

ObjectiveMultiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS); however, its underlying neurological pathogenic mechanisms remain incompletely understood. Endogenous formaldehyde (FA), a metabolic byproduct of methylation-demethylation cycles, has recently been implicated in neurotoxicity, oxidative damage, and cognitive impairment. This study aimed to investigate whether excessive FA contributes to myelin sheath demyelination in mice and to evaluate the protective effects and mechanisms of two FA-elimination strategies: sodium bisulfite (NaHSO₃), a classical FA scavenger, and polyethylene glycol-modified astaxanthin nanoparticles (PEG-ATX@NPs), a brain-targeted nano-antioxidant formulation. MethodsA chronic demyelination model was established by feeding female C57BL/6J mice a diet containing 0.2% cuprizone (CPZ) for four weeks, followed by a two-week intervention period. Eighty mice were randomly assigned to four groups: NS (normal saline), CPZ+NS, CPZ+NaHSO₃, and CPZ+PEG-ATX@NPs. Behavioral tests, including open-field, Y-maze, and pole-climbing assays, were conducted to assess locomotor activity, motor coordination, and working memory. FA levels in serum, corpus callosum, and spinal cord were measured using an Na-FA fluorescent probe and quantified via in vivo and ex vivo fluorescence imaging. Neuroinflammatory responses were evaluated by measuring TNF-α, IL-1β, and IL-6 levels using ELISA, while oxidative stress was assessed by reactive oxygen species (ROS) fluorescence intensity. Demyelination was examined via Luxol fast blue staining, and microglial activation was analyzed by Iba1 immunofluorescence. Correlation analyses were performed to explore relationships among FA levels, inflammatory cytokines, ROS intensity, and behavioral parameters. ResultsCompared with the NS group, mice in the CPZ+NS group exhibited significant weight loss, impaired motor coordination and memory, and markedly reduced myelin regeneration (P<0.05). FA levels and pro-inflammatory cytokines were significantly elevated in serum, corpus callosum, and spinal cord (P<0.05). FA-associated fluorescence in brain and spinal tissues, as well as ROS intensity across all tissues examined, also increased substantially (P<0.05). CPZ treatment induced pronounced microglial activation and severe demyelination in the corpus callosum (P<0.01). Both NaHSO₃ and PEG-ATX@NPs effectively reduced FA accumulation in the brain and spinal cord, attenuated demyelination, suppressed microglial activation, decreased inflammatory cytokine levels, and improved motor and cognitive performance. These results confirm that CPZ induced severe demyelination accompanied by oxidative stress, neuroinflammation, and abnormal FA accumulation. Following intervention with either NaHSO₃ or PEG-ATX@NPs, endogenous FA levels in the CNS were substantially reduced. Both treatments alleviated demyelination and significantly decreased the number of activated microglia. Levels of TNF-α, IL-1β, and IL-6 in serum, corpus callosum, and spinal cord were downregulated. Behavioral performance improved significantly, as evidenced by enhanced locomotor activity, better coordination, and improved memory function. These findings indicate that both FA-scavenging agents mitigate CPZ-induced biochemical and behavioral abnormalities. ConclusionThis study demonstrates that excessive endogenous FA is closely associated with cognitive impairment, inflammatory dysregulation, and demyelination in a CPZ-induced chronic demyelination mouse model. Clearing abnormally elevated FA effectively reduces neuroinflammation, suppresses microglial overactivation, decreases oxidative stress, and alleviates demyelination, ultimately improving motor and cognitive outcomes in mice. These results suggest that targeting endogenous FA represents a promising therapeutic strategy for MS and other demyelinating disorders. Further investigations are warranted to explore the long-term safety, dosage optimization, and molecular pathways involved in FA-mediated neurotoxicity.

OBJECTIVE To establish the UPLC fingerprint and the method for multi-component content determination in Jingangteng capsules， and to evaluate its quality by combining chemical pattern recognition analysis. METHODS An UPLC method was established. Separation was performed on a Zorbax SB-C 18 Rapid Resolution HD column， with acetonitrile-0.1% formic acid as the mobile phase for gradient elution.Using the Similarity Evaluation System for Chromatographic Fingerprints of Traditional Chinese Medicines （2012 edition）， UPLC fi ngerprints were established for 10 batches of Jingangteng capsules， and similarity was evaluated. SPSS 22.0 and SIMCA 14.1 software were used to perform hierarchial-cluster analysis and orthogonal partial least squares discriminant analysis （OPLS-DA）， respectively. The same UPLC method was employed to determine the contents of chlorogenic acid， 3，5-dihydroxy-2-methylbenzoic acid-3- O -glucoside （M1）， caffeic acid， astilbin， oxyresveratrol， quercitrin and resveratrol in the 10 batches of samples. RESULTS A total of 17 common peaks were identified in UPLC fingerprints of the 10 batches of samples， of which 7 were identified as chlorogenic acid， M1， caffeic acid， astilbin， oxyresveratrol， quercitrin， and resveratrol. The similarities of 10 batches of samples ranged from 0.820 to 0.985. The results of hierarchial-cluster analysis showed that 10 batches of samples were grouped into four categories： S1-S4 formed one group， S5 and S6 formed another， S7， S8 and S10 formed a third， and S9 formed a fourth， consistent with the OPLS-DA results； the variable importance projection values for peaks 7， 10， 2， 16 （resveratrol）， 13 （oxyresveratrol）， 11， 6 （caffeic acid）， 5 （M1） and 15 （quercitrin） were ＞1. Quantitative analysis results showed that the contents of chlorogenic acid， M1， caffeic acid， astilbin， oxyresveratrol， quercitrin， and resveratrol were 1.650 8-4.213 7， 0.636 2-2.161 7， 0.031 0-0.086 5， 0.239 1-1.069 3， 0.211 9-1.104 0， 0.488 8-2.399 2， and 0.164 0-0.699 8 mg/g， respectively. CONCLUSIONS UPLC fingerprint and content determination methods established in this study are simple to operate， accurate， reliable and reproducible； when combined with chemical pattern recognition analysis， they can be used to evaluate the quality of Jingangteng capsules. Nine components， such as resveratrol， oxyresveratrol， caffeic acid， M1 and quercitrin， may serve as markers of quality variation.

ObjectiveTo explore the vascular endothelial injury in male mice caused by exposure to polystyrene microplastics （PS-MPs） and the intervention effect of luteolin on vascular remodeling. Additionally， to investigate the mechanism through the oxidative system and metabolomics. MethodsThirty-two C57BL/6 mice （6-8 weeks old） were randomly divided into the saline group （saline group）， the 0.1 mg/kg PS-MPs exposure group （0.1PS-MPs group）， the 1 mg/kg PS-MPs exposure group （1PS-MPs group）， and the 1 mg/kg PS-MPs + luteolin treatment group （1PS-MPs + Lut group）， with 8 mice in each group. After 8 weeks of intervention， the body weight， blood pressure， aortic organ coefficient， and aortic histopathological changes of mice in each group were detected； the total cholesterol （TC）， triglyceride （TG）， and high-density lipoprotein cholesterol （HDL-C） lipid metabolism-related indicators in the aorta of mice were detected； the reactive oxygen species （ROS）， glutathione （GSH）， and malondialdehyde （MDA） oxidative stress-related indicators were detected； the endothelin （ET-1）， nitric oxide （NO）， vascular endothelial growth factor A （VEGF-A）， vascular cell adhesion molecule-1 （VCAM-1/CD106）， and intercellular adhesion molecule-1 （ICAM-1/CD54） endothelial function-related indicators and serum metabolomics were detected. ResultsCompared to the saline group， exposure to PS-MPs resulted in pathological thickening of the mouse aorta， increased aortic organ coefficient， and elevated blood pressure. Lipid metabolism-related indicators， including TC and TG， were elevated， while HDL-C was reduced， indicating lipid metabolism disorder in mice. Oxidative stress markers such as ROS and MDA increased， whereas GSH decreased， demonstrating oxidative damage. Vascular endothelial inflammation and injury markers， including ET-1， VEGF-A， VCAM-1， and ICAM-1， were upregulated， while the vasodilatory substance NO was downregulated， confirming endothelial injury. Furthermore， serum metabolomics results revealed that PS-MPs exposure induced endothelial damage by disrupting metabolic pathways such as the citrate cycle. Compared to the PS-MPs group， luteolin significantly reversed these effects， attenuating oxidative stress and lipid metabolism disorders， and effectively repairing endothelial injury. ConclusionPS-MPs induce vascular toxicity through oxidative stress and lipid metabolism. Luteolin effectively alleviates endothelial damage and vascular remodeling.

Objective To analyze the risk factors for chronic cough following pulmonary surgery in patients with non-small cell lung cancer (NSCLC). Methods A retrospective analysis was conducted on 427 NSCLC patients who underwent pulmonary surgery in the Department of Thoracic Surgery, The First Affiliated Hospital of the University of Science and Technology of China, between January 2021 and June 2023. Patients were categorized into a chronic cough group (103 patients) and a non-chronic cough group (324 patients) based on the presence of cough at 8 weeks post-surgery. A comparative analysis was performed between the two groups, considering gender, age, smoking history, comorbidities, preoperative pulmonary function indicators, pleural adhesion, anesthesia duration, surgical site, operative techniques, lymph node dissection methods, tumor maximum diameter, and postoperative chest tube duration. Factors showing statistical significance in univariate analysis underwent multivariate logistic regression analysis. Results Among the 427 patients undergoing pulmonary surgery, there were 165 males and 262 females, with an average age of (59.93±12.11) years. The incidence of chronic cough was 24.12%. Univariate analysis revealed significant differences in smoking history, preoperative pulmonary function indicators, pleural adhesion, anesthesia duration ≥135.5 minutes, surgical site, operative techniques, lymph node dissection methods, tumor maximum diameter, and postoperative chest tube duration (P<0.05). Multivariate logistic regression analysis indicated that the surgical site (right upper lung), operative techniques (lobectomy), lymph node dissection, and anesthesia time ≥135.5 minutes were independent risk factors for chronic cough following pulmonary surgery. Conclusion Patients undergoing right upper lung surgery, lobectomy, lymph node dissection, and experiencing anesthesia duration ≥135.5 minutes are at a higher risk of developing chronic cough post-pulmonary surgery.

ObjectiveTo explore the safety and efficacy of robot-assisted minimally invasive esophagectomy （robot-assisted minimally invasive esophagectomy， RAMIE） and thoracic laparoscopy combined with minimally invasive esophageal resection （minimal invasive esophagectomy， MIE）. MethodsThe data of 188 patients treated with Da Vinci robot assisted minimally invasive esophageal resection （RAMIE） from April 2021 to December 2022 were analyzed. In the RAMIE group， 69 patients， 49 males and 20 female， age （67.2 ± 7.2）； 119 in the MIME group， respectively， 89 males and 30 female， age （69.1 ± 7.0）. At 1 ∶ 1， including 58 patients in the RAMIE group and 58 patients in the MIE group. The t-test， Wilcoxon rank-sum test， χ² test， and so on. ResultsAfter PSM treatment， the clinical data between the two groups. There was no significant difference in operation time， postoperative tube days， and total number of lymph node dissection between the RAMIE and MIE groups （P <0.05）； the RAMIE group was better in terms of intraoperative bleeding and the MIE group， statistically significant （P <0.05）； the MIE group was better in drainage flow and lymph node dissection for three days （P <0.05）. In terms of postoperative complications， there was no statistical difference between RAMIE and MIE groups （P>0.05）. ConclusionThe recent efficacy of robot-assisted minimally invasive esophagectomy is comparable to that of thoracic laparoscopy and minimally invasive Mckeown esophagectomy； robotic-assisted minimally invasive esophagectomy can reduce intraoperative bleeding and have more advantages in left recurrent laryngeal nerve lymph node dissection.

Objective: To explore the effect and mechanism of lycorine on oxaliplatin ( OXA) induced chemotherapy pain in mice． Methods : 40 mice were randomly divided into 4 groups，10 mice per group，which were respectively divided into control group，model group，administration group，and inhibitor group．A mouse model of chemotherapy induced pain was established by intraperitoneal injection of OXA for 5 consecutive days．Intrathecal administration of lycorine was performed．Behavioral changes and expression levels of inflammatory related proteins were detected . Results : Compared with control group，model group mice exhibited the increased number of spontaneous flinches，decreased mechanical nociceptive threshold，decreased movement distance and latency，and up-regulated expression levels of interleukin-1 β (IL-1 β) ，astrocytic marker glial fibrillary acidic protein ( GFAP) ，cyclooxygenase-2( COX-2) ，NOD-like receptor protein 3 ( NLRP3 ) ，cysteinyl aspartate and specific proteinase 1 ( Caspase- 1) ．Compared with model group，lycorine administration reduced the number of spontaneous flinches，increased mechanical nociceptive threshold ，enhanced the movement distance and latency ，bound and reduced COX-2 expression，down-regulated the expression levels of IL-1 β , GFAP ，NLRP3 and Caspase-1． Conclusion Lycorine reduces COX-2 expression，inhibits NLRP3 inflammasome activation，suppresses spinal inflammation，consequently alleviates pain behaviors and improved motor ability of mice.

BACKGROUND: Pre-operative accuracy of subcentimeter ground glass nodules (SGGNs) is a difficult problem in clinical practice, but there are few clinical studies on the benign and malignant prediction model of SGGNs. The aim of this study was to help identify benign and malignant lesions of SGGNs based on the imaging features of high resolution computed tomography (HRCT) and the general clinical data of patients, and to build a risk prediction model. METHODS: This study retrospectively analyzed the clinical data of 483 patients with SGGNs who underwent surgical resection and were confirmed by histology from the First Affiliated Hospital of University of Science and Technology of China from August 2020 to December 2021. The patients were divided into the training set (n=338) and the validation set (n=145) according to 7:3 random assignment. According to the postoperative histology, they were divided into adenocarcinoma group and benign lesion group. The independent risk factors and models were analyzed by univariate analysis and multivariate Logistic regression. The receiver operator characteristic (ROC) curve was constructed to evaluate the model differentiation, and the calibration curve was used to evaluate the model consistency. The clinical application value of the decision curve analysis (DCA) evaluation model was drawn, and the validation set data was substituted for external verification. RESULTS: Multivariate Logistic analysis screened out patients' age, vascular sign, lobular sign, nodule volume and mean-CT value as independent risk factors for SGGNs. Based on the results of multivariate analysis, Nomogram prediction model was constructed, and the area under ROC curve was 0.836 (95%CI: 0.794-0.879). The critical value corresponding to the maximum approximate entry index was 0.483. The sensitivity was 76.6%, and the specificity was 80.1%. The positive predictive value was 86.5%, and the negative predictive value was 68.7%. The benign and malignant risk of SGGNs predicted by the calibration curve was highly consistent with the actual occurrence risk after sampling 1,000 times using Bootstrap method. DCA showed that patients showed a positive net benefit when the predictive probability of the predicted model probability was 0.2 to 0.9. CONCLUSIONS Based on preoperative medical history and preoperative HRCT examination indicators, the benign and malignant risk prediction model of SGGNs was established to have good predictive efficacy and clinical application value. The visualization of Nomogram can help to screen out high-risk groups of SGGNs, providing support for clinical decision-making.
Humans ; Retrospective Studies ; Lung Neoplasms/surgery* ; Adenocarcinoma ; China ; Hospitals ; Multiple Pulmonary Nodules

Background Dibutyl phthalate (DBP) is a common plasticizer in daily life and has been proved to be related to the exacerbation of allergic asthma. Domestic and foreign studies have shown that lipid peroxidation is closely related to the severity of asthma, which can be used as a basis for the diagnosis and treatment of asthma. Whether DBP can induce lipid peroxidation in allergic asthma remains to be further studied. Objective To investigate whether DBP aggravates allergic asthma by inducing lipid peroxidation in allergic asthma mice. Methods Eighty male BALB/c mice were randomly divided into 4 groups, namely control group, DBP group (40 mg·kg⁻¹), 50 μg ovalbumin (OVA) group (allergic asthma model group), and DBP+OVA group. The DBP group and the DBP+OVA group were given DBP by gavage from Day 1 to 28, and the OVA group and the DBP+OVA group were sensitized by intraperitoneal injection of OVA, once every 3 d, a total of 5 injections, from Day 9 to 21. From Day 29 to 35, the OVA group and the DBP+OVA group were challenged by OVA atomization. After the exposure, samples of blood and lung were collected. The airway hyperresponsiveness of mice was observed by lung function analysis. The serum contents of immunoglobulin E (IgE), OVA-specific immunoglobulin E (OVA-IgE), and lung homogenate levels of interleukin 4 (IL-4) were detected by enzyme-linked immunosorbent assay (ELISA) to evaluate airway allergic inflammation. The pathological changes of lung tissues were observed after hematoxylin-eosin (HE) staining and collagen fiber (Masson) staining. The contents of reactive oxygen species (ROS), lipid ROS, glutathione peroxidase 4 (GPX4), reduced glutathione (GSH), malondialdehyde (MDA), and 4-hydroxynonenal (4-HNE) in lung homogenates were detected by ELISA to evaluate lipid peroxidation. Results The results of lung function analysis showed that compared with the control group, the inspiratory resistance (Ri) and expiratory resistance (Re) of the OVA group and the DBP+OVA group were increased, and the lung compliance (Cldyn) was decreased. The DBP + OVA group was more severe, and the difference between the OVA group and the DBP + OVA group was statistically significant (P<0.05 or P<0.01). Compared with the control group, the contents of IgE, OVA-IgE, and IL-4 in the OVA group and the DBP+OVA group were increased (P<0.05 or P<0.01), which indicated more severe allergic airway inflammation. The HE sections of the OVA group and the DBP+OVA group showed inflammatory cell infiltration around the airway, airway wall hyperplasia and thickening, and severe airway deformation, and the presentation of the DBP+OVA group was the most serious. After Masson staining, the OVA group and the DBP+OVA group showed depositions of a large number of collagen fibers, and the blue collagen fibrosis in the DBP+OVA group was even more serious. ROS, lipid ROS, MDA, and 4-HNE levels increased and GSH and GPX4 levels decreased in the OVA and DBP+OVA groups (P<0.05 or P<0.01), with the most severe effect in the DBP+OVA group. Conclusion DBP may induce lipid peroxidation in mice allergic asthma by producing excessive ROS which may aggravate the allergic asthma in mice.

BACKGROUND: Small pulmonary nodules are usually difficult to identify during thoraco-scopic resection, and preoperative computed tomography (CT)-guided percutaneous puncture assisted localization can be helpful. The purpose of this study is to compare the localization effect and complication rates of two different methods by microcoil placement and sclerosing agent injection (Lauromacrogol). METHODS: A retrospective analysis of the clinical data of 371 patients with preoperative pulmonary nodules percutane us puncture localization was performed. According to the use of different materials, they were divided into the microcoil group (167 cases with 196 localized nodules ) and the sclerosing agent group (204 cases with 239 localized nodules). The localization effect, complication, pathological results and operation relates data were statistically analyzed. RESULTS: The localization failure rate (2.4%) was higher in the microcoil group than in the sclerosing agent group (0.5%) (P=0.011), and the localization time of sclerosing agent group was significantly shorter than the microcoil group [(18.78±6.91) min vs (11.99±3.77) min, P=0.000], but the distance between the selected localized nodules and the pleura was deeper in the microcoil group than in the sclerosing agent group [(9.59±8.62) mm vs (8.13±6.49)mm, P=0.002]. The overall complications in the microcoil group were significantly higher than those in the sclerosing agent group (P=0.000), in which pneumothorax was the most common. Through the analysis of related risk factors, we revealed that different positioning methods was independent risk factors. Wedge resection was the main type of surgical method and non-invasive carcinomas were the majority of postoperative pathological results. CONCLUSIONS Our study suggests that both microcoil placement and sclerosing agent injection are suitable for preoperative pulmonary nodule localization equivalently, however, compared with microcoils placement, injection of lauromacrogol, the sclerosing agent, had lower failure rate, less complications, shorter localization time and it is worthy of promotion also by easy operation and low cost.