ObjectiveThis study aims to systematically analyze the blood-absorbed components and metabolic profiles of Xiebaisan（XBS） in normal and chronic bronchitis （CB） mice using ultra performance liquid chromatography-quadrupole-electrostatic field orbitrap high resolution mass spectrometry（UPLC-Q-Exactive Orbitrap MS）， while comparing differences between the two states. MethodsThirty female BABL/c mice were randomly divided into the normal group， the normal drug administration group， the CB group， the CB drug administration group and the dexamethasone group， with 6 mice in each group. The CB mouse model was established by inducing with ovalbumin （OVA）. The mice in the normal drug administration group and the CB drug administration group started to be gavaged with XBS（13.2 g·kg^-1） from the 21^st day， and the dexamethasone group mice were simultaneously gavaged with dexamethasone （0.5 mg·kg^-1） until the end of the 35^th day of the experiment. Subsequently， serum samples were collected and evaluated for their efficacy， based on the pharmacological evaluation indicators， to determine the efficacy of XBS in treating CB. Then the UPLC-Q-Exactive Orbitrap MS was employed to identify and analyze the chemical constituents， blood-absorbed components， and metabolites of XBS. Chemometric analysis was conducted to reveal metabolic profile differences under "dual states". Concurrently， Real-time PCR technology was utilized to detect the expression levels of key liver metabolic enzymes CYP2E1， CYP3A1， UGT1A1， and UGT1A6. ResultsA total of 28 prototype components and 158 metabolites （including 48 phase Ⅰ metabolites and 110 phase Ⅱ metabolites） of XBS were unambiguously identified in the serum of normal mice. Additionally， a comprehensive characterization was performed on a total of 32 prototype components and 178 metabolites （including 50 phase Ⅰ metabolites and 128 phase Ⅱ metabolites） of XBS in the serum of CB mice. Among them， 27 prototype components were detected in both states， including 12 flavonoids， 2 alkaloids， 3 triterpenes， 4 organic acids， 3 amides， 1 stilbene and 2 other compounds. The chemometrics analysis revealed no significant difference in the prototype components and metabolites of XBS between normal and CB mice； however， there was a significant increase in the in-vivo exposure of XBS in CB mice. Compared to normal mice， the levels of phase Ⅰ metabolites such as oxidation， reduction and methylation of blood components of XBS as well as phase Ⅱ metabolites of glucuronidation showed significant changes in CB mice. Real-time PCR further confirmed that these alterations were attributed to the upregulation of CYP2E1 （P<0.05）， CYP3A1 （P>0.05）， UGT1A1 （P<0.01） and UGT1A6 （P<0.01） enzymes expression in the liver of CB mice. ConclusionThis study elucidated the disparities in the levels of the blood-absorbed components and metabolic profiles of XBS in normal and CB mice， especially in oxidation， reduction， methylation in phase Ⅰ metabolism and glucoaldehyde acidification in phase Ⅱ metabolism. And there are related to the differences in the expression levels of phase Ⅰ and phase Ⅱ metabolic enzymes CYP2E1， CYP3A1， UGT1A1 and UGT1A6 in the liver.

ObjectiveThis paper aims to investigate the role of NDC80 kinetochore complex component （NUF2） and magnesium homeostasis in ovarian cancer cell apoptosis， as well as the regulatory mechanism of gypenoside L （Gyp-L） on NUF2 and magnesium homeostasis. MethodsOvarian cancer OVCAR3 cells were divided into a blank control group， a low-concentration Gyp-L group （50 µmol·L^-1）， a high-concentration Gyp-L group （100 µmol·L^-1）， and a cisplatin （15 µmol·L^-1） group. The migration， proliferation， and apoptosis capabilities of OVCAR3 cells were evaluated through cell scratch assays， clonal experiments， and terminal-deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay （TUNEL） staining. Differentially expressed genes of ovarian cancer were screened by using the Gene Expression Omnibus （GEO） database. The interaction relationships of differentially expressed genes and proteins were analyzed via the Search Tool for Recurring Instances of Neighbouring Genes （STRING） database. The prognostic survival analysis was performed by using the Tumor Immune Estimation Resource （TIMER） database， and the differential expression levels of genes were validated with the Gene Expression Profiling Interactive Analysis （GEPIA） database. The mRNA expression levels of NUF2， magnesium homeostasis-related indicators， such as magnesium transporter 1 （MAGT1）， non-imprinted in Prader-Willi/Angelman syndrome 1 （NIPA1）， NIPA-like domain containing 1 （NIPAL1）， as well as apoptosis-related indicators B cell lymphoma-2 （Bcl-2） and Bcl-2-associated X protein （Bax） in OVCAR3 cells， were detected by real-time quantitative polymerase chain reaction （Real-time PCR）. The protein expression levels of NUF2， MAGT1， NIPA1， NIPAL1， Bcl-2， and Bax in OVCAR3 cells were quantitatively analyzed by ProteinSimple WES. A model of overexpression of NUF2 was constructed， and Gyp-L intervention was performed. The molecular mechanism by which Gyp-L induces ovarian cancer cell apoptosis by regulating NUF2 and influencing magnesium homeostasis was quantitatively analyzed and detected through cell cloning， TUNEL staining， Real-time PCR， and ProteinSimple WES. Finally， the Mg²⁺ content and protein synthesis efficiency were detected by immunofluorescence. ResultsGyp-L significantly inhibited the migration and proliferation capabilities of OVCAR3 cells and promoted their apoptosis （P<0.05）. Overexpression of NUF2 markedly increased the expression levels of MAGT1， NIPA1， NIPAL1， and Bcl-2， while reducing the expression level of Bax （P<0.05）. It also significantly elevated intracellular Mg²⁺ content and protein synthesis efficiency and simultaneously inhibited apoptosis （P<0.05）. Gyp-L could reverse the magnesium homeostasis imbalance and apoptosis inhibition caused by the overexpression of NUF2， downregulating the expression levels of NUF2， MAGT1， NIPA1， NIPAL1， and Bcl-2 （P<0.05）， while upregulating the expression level of Bax （P<0.05）. ConclusionGyp-L can inhibit the occurrence of ovarian cancer， and its mechanism may involve inhibiting the expression of NUF2 to maintain magnesium homeostasis and inducing apoptosis of ovarian cancer cells.

Objective: To explore the association between mental health and muscle strength among Chinese adolescents aged 13- 18, providing a theoretical foundation and intervention strategies for mental health promotion. Methods: Data were obtained from the 2019 Chinese National Survey on Students Constitution and Health, including 98 631 Chinese adolescents aged 13- 18. Psychological distress was assessed by using the Kessler Psychological Distress Scale (K10), and mental well being was measured with the Warwick-Edinburgh Mental Well being Scale (WEMWBS). Based on the gender and age specific Z scores of various test items [grip strength, standing long jump, pull ups (for males), and sit ups (for females)], muscle strength index (MSI) was constructed to evaluate the comprehensive level of muscle strength in adolescents. According to the Dual factor Model (DFM) of mental health, participants were categorized into four groups:troubled, symptomatic but content, vulnerable, and complete mental health. Gender differences were analyzed by using Chi-square tests, trends were tested with Cochran-Armitage tests, and multinomial Logistic regression models were applied to assess associations between muscle strength and mental health among adolescents. Results: In 2019, 37.4% of Chinese adolescents aged 13-18 were reported of high mental distress, and 59.9% were reported of low mental well being. Boys had significantly lower rates of high mental distress (35.3%) and low mental well being (55.6%) compared to girls (39.4%, 64.3%), and the differences were of statistical significance ( χ 2=176.13, 780.42, both P <0.05). In 2019, the rate of complete mental health among adolescents showed a downward trend with increasing age ( χ 2 trend = 258.47) and a gradual upward trend with increasing muscle strength levels ( χ 2 trend =123.14)，and both boys and girls exhibited similar trends ( χ 2 trend =103.83, 168.46; 57.00 , 67.34) (all P <0.05). The results of the unordered multiclass Logistic regression model showed that after controlling for confounding factors such as age and gender, when the completely pathological group as a reference, for every 1 unit increase in MSI in adolescents, the likelihood of being in a completely mental health state increased by 29% ( OR = 1.29); for every unit increase in the Z-score for pull ups, the likelihood of being in a completely mental health state increased by 6% ( OR =1.06) among boys; for every 1 unit increase in sit up Z score, the likelihood of being in a completely mental health state increased by 19% ( OR =1.19) among girls (all P <0.05). Conclusions The mental health status of Chinese adolescents is not good enough. Muscle strength is positively associated with mental health.

Objective: To systematically review the development and changes in mental health policies within the National Outline for Children s Development in China from 1992 to 2030, providing a reference basis for future formulation of mental health policies among children and adolescent in China. Methods: Based on the four editions of the National Outline for Children s Development in China across different periods from 1992 to 2030, word frequency analysis was used to reveal shifts in policy priorities, and an internationally recognized framework for adolescent health policy analysis was applied to conduct a textual review. Results: Word frequency analysis revealed that the term "psychological" appeared 6 times in the National Outline for Children s Development in China (2001-2010) but increased to 20 times in the National Outline for Children s Development in China (2021-2030) (abbreviated as the National Outline of 2021), while the term "health" rose from 4 times in the National Outline for Children s Development Plan in China in the 1990s to 68 times in the National Outline of 2021. The scope of mental health policy interventions expanded to encompass five key areas:health, safety, education, welfare and legal protection. Textual analysis highlighted that the policies of the National Outline for Children s Development in China were demand driven, prioritized vulnerable groups and continuously broadened their coverage, emphasizing sustainability and appropriateness, and monitoring/evaluation mechanisms. By 2023, 42.3% of primary schools and 64.8% of secondary schools employed full time mental health education teachers. However, the National Outline for Children s Development in China lacked direct evidence of children and adolescents participation in policy formulation, and publicly available mental health data disaggregated by age and gender remained limited. Conclusion Mental health policies of children and adolescents in China have evolved from nonexistence to gradual refinement, yet institutionalized channels for youth involvement in policy development and evaluation remain insufficient, and transparency in age and gender specific mental health data needs improvement.

OBJECTIVE: To explore the preparation of nano-silver acupuncture needles and evaluate the appearance, structure and properties. METHODS: Stainless steel acupuncture needles were pretreated by polishing with sandpaper and cleaning with ultrapure water and absolute ethanol. As the working electrodes, the needles were placed in an electrolyte solution contained silver nitrate (AgNO₃), potassium nitrate (KNO₃), and polyvinylpyrrolidone (PVP); and the silver nanoparticles were deposited at a constant voltage of -0.2 V for 1 200 s. The heat-treatment was conducted at 600 ℃ for 15 min in an argon atmosphere to strengthen the adhesion between the nanoparticles and the substrate. The surface appearance and structure of nano-silver acupuncture needles were characterized by scanning electron microscopy (SEM), X-ray diffraction (XRD) and X-ray photoelectron spectroscopy (XPS). The electrical conductivity, thermal conductivity and biocompatibility of the needles were evaluated. The cytotoxicity and biocompatibility of the sample were assessed using the CCK-8 assay. According to the national standard, Acupuncture Needles (GB 2024-2016), the other physicochemical performances of nano-silver acupuncture needles were tested. RESULTS: ①By controlling the AgNO₃ concentration and the molar ratio of AgNO₃ to PVP, it was found that at an AgNO₃ concentration of 2 mmol/L and a molar ratio of 5∶1, silver nanoparticles with the diameter of 50-100 nm, regular appearance, and uniform distribution were obtained. At a lower concentration, the size of silver nanoparticles was smaller and unevenly distributed particles, whereas a higher concentration tended to produce a dendritic structure. ②By sandpaper polishing, acid etching pretreatment, and heat-treatment at 600 ℃ under argon for 15 min, the adhesion of silver nanoparticles on the surface of the needle body was strengthened, and the simulated pig skin puncture test showed the intact coating without shedding. ③SEM found that the silver nanoparticles were uniformly deposited, forming a nanofilm approximately 1.5 μm thick; XRD analysis showed the diffraction peaks corresponding to cubic crystal silver (111), (200), (220) and (311); and XPS detected characteristic peaks of Ag 3d3/2 and Ag 3d5/2, confirming the successful deposition and good crystallinity of the silver nanoparticles. ④Resistivity measurements indicated that the nano-silver acupuncture needles exhibited a resistivity of approximately 0.15 Ω·cm, about three times lower than that of unmodified stainless steel needles. The infrared thermography demonstrated that their thermal conductivity was superior to that of traditional acupuncture needles. In vitro CCK-8 cytotoxicity assay showed that the nano-silver acupuncture needles had no adverse effects on human skin fibroblasts and possessed good biocompatibility. ⑤ The key parameters such as needle tip performance, hardness, and the adhesion between the needle body and handle were in compliance with the requirements in Acupuncture Needles (GB 2024-2016), ensuring a quality guarantee provided for clinical applications. CONCLUSION The preparation of nano-silver acupuncture needles effectively overcomes the insufficient toughness of traditional silver needles and improves the electrical and thermal conductivity of stainless acupuncture needles.
Silver/chemistry* ; Needles ; Acupuncture Therapy/instrumentation* ; Metal Nanoparticles/chemistry* ; Humans ; Electric Conductivity ; Animals

BACKGROUND: Epoxyeicosatrienoic acids (EETs), which are metabolites of arachidonic acid catalyzed by cytochrome P450 epoxygenase, are degraded into inactive dihydroxyeicosatrienoic acids by soluble epoxide hydrolase (sEH). Many studies have revealed that sEH gene deletion exerts protective effects against diabetes. Vascular calcification is a common complication of diabetes, but the potential effects of sEH on diabetic vascular calcification are still unknown. METHODS: The level of aortic calcification in wild-type and Ephx2-/- C57BL/6 diabetic mice induced with streptozotocin was evaluated by measuring the aortic calcium content through alizarin red staining, immunohistochemistry staining, and immunofluorescence staining. Mouse vascular smooth muscle cell lines (MOVAS cells) treated with β-glycerol phosphate (0.01 mol/L) plus advanced glycation end products (50 mg/L) were used to investigate the effects of sEH inhibitors or sEH knockdown and EETs on the calcification of vascular smooth muscle cells, which was detected by Western blotting, alizarin red staining, and Von Kossa staining. RESULTS: sEH gene deletion significantly inhibited diabetic vascular calcification by increasing levels of EETs in the aortas of mice. EETs (especially 11,12-EET and 14,15-EET) efficiently prevented the osteogenic transdifferentiation of MOVAS cells by decreasing nidogen-2 (NID2) expression. Interestingly, suppressing sEH activity by small interfering ribonucleic acid or specific inhibitors did not block osteogenic transdifferentiation of MOVAS cells induced by β-glycerol phosphate and advanced glycation end products. NID2 overexpression significantly abolished the inhibitory effect of sEH gene deletion on diabetic vascular calcification. Moreover, NID2 overexpression mediated by adeno-associated virus 9 vectors markedly increased insulin-like growth factor 2 (IGF2) and phospho-ERK1/2 expression in MOVAS cells. Overall, sEH gene knockout inhibited diabetic vascular calcification by decreasing aortic NID2 expression and, then, inactivating the downstream IGF2-ERK1/2 signaling pathway. CONCLUSIONS sEH gene deletion markedly inhibited diabetic vascular calcification through repressed osteogenic transdifferentiation of vascular smooth muscle cells mediated by increased aortic EET levels, which was associated with decreased NID2 expression and inactivation of the downstream IGF2-ERK1/2 signaling pathway.
Animals ; Mice ; Vascular Calcification/metabolism* ; Mice, Inbred C57BL ; Epoxide Hydrolases/metabolism* ; Diabetes Mellitus, Experimental/genetics* ; Male ; Gene Deletion ; MAP Kinase Signaling System/genetics* ; Cell Line ; Immunohistochemistry ; Muscle, Smooth, Vascular/metabolism* ; Signal Transduction/genetics* ; Mice, Knockout

Ten novel xanthones, garpedunxanthones A-G (1-5, 6a/6b, 7a/7b) and nujiangxanthone Q (8), along with sixteen known analogs (9-24), were isolated from Garcinia pedunculata and G. nujiangensis. Their structures were elucidated through high-resolution electrospray ionization mass spectrometry (HR-ESI-MS) data, comprehensive nuclear magnetic resonance (NMR) spectroscopic analyses, and electronic circular dichroism (ECD) calculations. All compounds without cytotoxicity were assessed for anti-inflammatory properties by measuring the inhibition of nitric oxide (NO) production in lipopolysaccharide (LPS)-induced RAW264.7 cells. Structure-activity relationships are also discussed. Compounds 7b, 19, and 21 exhibited significant anti-inflammatory activity with IC₅₀ values of 16.44 ± 0.69, 14.28 ± 0.78, and 10.67 ± 3.28 μmol·L^-1, respectively. Enzyme-linked immunosorbent assay (ELISA) demonstrated that compounds 7b, 19, and 21 inhibited the expression of pro-inflammatory cytokines TNF-α and IL-6 in a dose-dependent manner. The inhibitory effect of compound 21 on IL-6 at 20 μmol·L^-1 was comparable to that of the positive control. In network pharmacology studies, potential targets of compounds and inflammation were identified from PharmMapper and GeneCards databases. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed that the overlapped targets were intricately associated with major pathogenic processes linked to inflammation, including positive regulation of mitogen-activated protein kinase (MAPK) cascade, protein kinase activity, NO synthase regulator activity, MAPK signaling pathway, and EGFR tyrosine kinase inhibitor resistance.
Xanthones/therapeutic use* ; Garcinia ; Anti-Inflammatory Agents/therapeutic use* ; Plant Preparations/therapeutic use* ; Structure-Activity Relationship ; Nitric Oxide/metabolism* ; RAW 264.7 Cells ; Animals ; Mice ; Enzyme-Linked Immunosorbent Assay ; Mitogen-Activated Protein Kinase Kinases/metabolism* ; Circular Dichroism

A chemical investigation of secondary metabolites (SMs) from Aspergillus nidulans resulted in the identification of five novel dioxopiperazine (DKP)-diphenyl ether hybrids, designated as diphenylemestrins A-E (1-5). These compounds 1-5 represent the first known dimers combining DKP and diphenyl ether structures, with compound 4 featuring an uncommon dibenzofuran as the diphenyl ether component. The structural elucidation and determination of absolute stereochemistry were accomplished through spectroscopic analysis and electronic circular dichroism (ECD) calculations. Notably, diphenylemestrin C (3) exhibited moderate cytostatic activity against NB4 cells, with a half maximal inhibitory concentration (IC₅₀) value of 21.99 μmol·L^-1, and induced apoptosis at higher concentrations.
Aspergillus nidulans/metabolism* ; Diketopiperazines/pharmacology* ; Molecular Structure ; Phenyl Ethers/pharmacology* ; Humans ; Apoptosis/drug effects* ; Cell Line, Tumor

OBJECTIVE To compare the efficacy and safety of chemotherapy combined with tislelizumab or sintilimab in patients with advanced non-small cell lung cancer （NSCLC）， and to analyze the influential factors of prognostic. METHODS A retrospective study was conducted on 163 patients with advanced NSCLC who received chemotherapy combined with tislelizumab or sintilimab at the First People’s Hospital of Yunnan Province from September 1， 2021 to November 30， 2024. Among them， there were 90 patients in the tislelizumab group and 73 patients in the sintilimab group. The objective response rate （ORR）， disease control rate （DCR）， progression free survival （PFS）， and overall survival （OS） of two groups were observed， and the occurrence of adverse drug reactions in patients was evaluated. Kaplan-Meier method was used to plot PFS and OS survival curves， Log-rank test was applied for univariate analysis， and Cox regression model was used to evaluate the independent prognostic factors of PFS and OS. RESULTS The median PFS of patients in the tislelizumab group and the sintilimab group were 14.14 months （95%CI of 10.95-17.33） and 10.95 months （95%CI of 8.75-13.15）， respectively. The median OS was 25.89 months （95%CI of 22.67-29.11） and 24.25 months （95%CI of 19.34-29.16）， with ORR of 45.56% and 49.32%， DCR of 94.44% and 90.41%， and the incidence of adverse drug reactions of 84.44% and 79.45%， respectively， the differences were not statistically significant （P＞0.05）. Age ≥60 years （HR＝1.542， 95%CI of 1.044-2.278， P＝0.029） and systemic immune inflammatory nutritional index （SIINI）＞ 116.58 （HR＝1.541， 95%CI of 1.058-2.245， P＝0.024） were risk factors for PFS in NSCLC patients receiving immune checkpoint inhibitor therapy； the use of antibiotics may affect the overall survival of patients （P＝0.001）. CONCLUSIONS The efficacy and safety of chemotherapy combined with tislelizumab or sintilimab for advanced NSCLC are comparable； age≥60 years and SIINI ＞116.58 are risk factors for PFS in NSCLC patients， and the use of antibiotics may affect the patients’ OS.

Objective:To investigate the potential characteristic manifestations and application value of the Dynamic Visual Acuity Test（DVAT） in vestibular migraine（VM）. Methods:A total of 50 VM patients（case group） and 50 healthy subjects（control group） diagnosed at the Department of Otorhinolaryngology Head and Neck Surgery, First Hospital of Shanxi Medical University between November 1, 2023, and December 31, 2024, were enrolled. The case group underwent DVAT, video head impulse test（vHIT）, caloric test, and Dizziness Handicap Inventory（DHI） assessment, whereas the control group only received DVAT. Group-based analyses were conducted to examine the effect of age on Dynamic Visual Acuity Loss（DVALoss）, as well as the correlations of DVALoss with vestibular function tests and DHI scores. Results:DVALoss in the case group was significantly higher than that in the control group（P<0.001）. In both groups, age was significantly and positively correlated with DVALoss（P<0.001）. Within the case group, DVALoss was strongly and positively correlated with DHI scores（r=0.807, P<0.001）; it was negatively correlated with the vestibulo-ocular reflex（VOR） gain in vHIT, though without clinical significance, and showed no significant association with the caloric test. Age and DVALoss collectively accounted for 71.3% of the variance in DHI scores（R²=0.713）, with age exerting a relatively minor actual impact. Conclusion:DVAT can sensitively identify the core functional impairments of VM. DVALoss, as a direct functional reflection of the pathological mechanism of VM, is strongly correlated with DHI scores. Incorporating DVALoss into standardized assessments may provide an objective basis for the diagnosis and management of VM.
Humans ; Migraine Disorders/diagnosis* ; Visual Acuity ; Case-Control Studies ; Head Impulse Test ; Vestibular Function Tests ; Female ; Male ; Adult ; Vestibular Diseases/physiopathology* ; Middle Aged ; Caloric Tests