ObjectiveTo systematically characterize the in vitro chemical constituents of Entada phaseoloides and its absorbed prototype compounds and metabolites in a neuropathic pain （NP） model， thereby elucidating the potential pharmacological material basis underlying its analgesic activity. MethodsUltra-high-performance liquid chromatography coupled with quadrupole-Orbitrap high-resolution mass spectrometry （UHPLC-Q-Orbitrap HRMS） was used to analyze the constituents of the 80% methanol extract of E. phaseoloides. Thirty-six mice were divided into a blank group， low-， medium-， and high-dose E. phaseoloides extract groups （25， 50， and 100 mg·kg^-1， respectively）， an aspirin group （400 mg·kg^-1）， and a morphine group （10 mg·kg^-1）， with six mice in each group. The tail-flick threshold was measured. Twenty-four mice were randomly divided into a blank group and low-， medium-， and high-dose E. phaseoloides extract groups （25， 50， and 100 mg·kg^-1， respectively）， with six mice in each group， and motor coordination was evaluated. A spinal nerve ligation （SNL） model was established in mice. Twenty-four mice were randomly divided into a sham-operated （Sham） group， an SNL group， an SNL + E. phaseoloides extract group （750 mg·kg^-1）， and an SNL + pregabalin group （20 mg·kg^-1）， with 6 mice in each group. Mechanical allodynia and thermal hyperalgesia were evaluated. Behavioral assessments were combined to determine the optimal onset time of the analgesic effect， and plasma samples were collected at this time point. Absorbed components and metabolites were systematically identified based on accurate mass， MS/MS fragmentation patterns， retention time， and comparisons with literature data and reference standards. Meanwhile， network pharmacology， target similarity analysis， and molecular docking validation were integrated to evaluate the potential effects of absorbed components on disease intervention. ResultsCompared with the blank group， the high-dose E. phaseoloides extract group and morphine group showed significantly increased pain response thresholds （P<0.01）， without affecting motor coordination in normal mice. Compared with the Sham group， the SNL group exhibited significantly decreased thresholds for mechanical allodynia and thermal hyperalgesia （P<0.01）. Compared with the SNL group， the SNL + E. phaseoloides extract group and SNL + pregabalin group showed significantly increased thresholds for mechanical allodynia and thermal hyperalgesia （P<0.01）. The analgesic effect of E. phaseoloides was most significant at 2 h after administration. A total of 70 constituents were identified in vitro， and 22 prototype compounds and 29 metabolites were detected in plasma. The targets of the absorbed components were mainly enriched in biological processes associated with pain signal perception and transmission and showed a high degree of overlap with disease genes related to neuropathic pain. In addition， multiple components exhibited strong binding energies with core pain-related targets. Based on integrated analysis of in vitro content， plasma exposure levels， and target associations， ketanthamide A-β-D-pyranoside and ketengzide were identified as the most representative pharmacologically active substances responsible for the analgesic effect. ConclusionThis study systematically elucidates the material basis of E. phaseoloides intervention in neuropathic pain from three aspects， including chemical constituent characteristics， in vivo behavioral characteristics， and potential targets， providing important theoretical foundations and experimental support for further studies on its pharmacological mechanism and analgesic drug development.

Dry eyes,a condition that is more likely to be comorbid in patients with diabetes mellitus(DM),is an ocu-lar surface disease caused by a variety of factors,and it is mainly characterized by an imbalance of tear film stability and ocular discomfort.The pathogenesis of this disease is complex,mainly involving peripheral corneal neuropathy,changes in tear composition and osmolarity,decreased tear film stability,and ocular surface inflammation.The cyclic guanosine monophosphate-adenosine monophosphate synthase(cGAS)-stimulator of interferon genes(STING)signaling pathway plays a key role in the inflammatory response:corneal oxidative stress may lead to mitochondrial damage,and damaged mi-tochondrial DNA(mtDNA)is released into the cytoplasm to activate the cGAS-STING pathway,which triggers the release of interferon and the aggravation of inflammation.This article reviews the pathological mechanisms of dry eyes in DM and explores the regulatory role of the cGAS-STING pathway in the pathogenesis of this disease,thus providing new targets and strategies for the treatment of this disease.

Purpose To explore the characteristics of gray matter(GM)volume changes in migraine patients using 7T MRI and voxel-based morphometry(VBM).Materials and Methods This prospective study enrolled 30 migraine patients and 41 age-and gender-matched healthy controls from Beijing Tiantan Hospital,Capital Medical University between November 2023 and November 2024.All participants underwent 7T MRI with 3D T1-weighted magnetization-prepared two rapid gradient-echo(MP2RAGE)sequences for structural brain imaging.VBM analysis was performed to quantify GM,white matter,cerebrospinal fluid and total brain volumes,followed by calculations of their relative percentages.The difference in GM volume between the two groups was compared to identify brain regions with characteristic GM volume changes in migraine patients.And the correlation between these characteristic GM volume alterations and clinical scales was analyzed.Results Migraine patients exhibited significantly lower total GM volume compared to healthy controls(t=2.096,P=0.040),while no group differences were observed in white matter or cerebrospinal fluid volumes(t=0.980,0.151;P=0.330,0.880).VBM analysis revealed reduced GM volume in the left orbitofrontal cortex(t=4.301,P=0.022),left hippocampus(t=5.226,P=0.006)and left parahippocampal gyrus(t=3.960,P=0.040)in the migraine group.Negative correlations were identified between:left orbitofrontal cortex GM volume and headache duration(r=-0.506,P=0.008),left hippocampal GM volume and patient health questionnaire-9 scores(r=-0.620,P=0.003),and left parahippocampal GM volume and visual analogue scale scores(r=-0.449,P=0.019).Conclusion VBM analysis based on 7T MP2RAGE data demonstrates characteristic GM volume reductions in the left orbitofrontal cortex,left hippocampus and left parahippocampal gyrus in migraine patients,with these structural alterations significantly correlate with depressive symptoms and headache burden.The observed microstructural abnormalities may reflect underlying pathophysiological mechanisms related to pain processing,emotional regulation and long-term disease burden in migraine.

Dry eyes,a condition that is more likely to be comorbid in patients with diabetes mellitus(DM),is an ocu-lar surface disease caused by a variety of factors,and it is mainly characterized by an imbalance of tear film stability and ocular discomfort.The pathogenesis of this disease is complex,mainly involving peripheral corneal neuropathy,changes in tear composition and osmolarity,decreased tear film stability,and ocular surface inflammation.The cyclic guanosine monophosphate-adenosine monophosphate synthase(cGAS)-stimulator of interferon genes(STING)signaling pathway plays a key role in the inflammatory response:corneal oxidative stress may lead to mitochondrial damage,and damaged mi-tochondrial DNA(mtDNA)is released into the cytoplasm to activate the cGAS-STING pathway,which triggers the release of interferon and the aggravation of inflammation.This article reviews the pathological mechanisms of dry eyes in DM and explores the regulatory role of the cGAS-STING pathway in the pathogenesis of this disease,thus providing new targets and strategies for the treatment of this disease.

Purpose To explore the characteristics of gray matter(GM)volume changes in migraine patients using 7T MRI and voxel-based morphometry(VBM).Materials and Methods This prospective study enrolled 30 migraine patients and 41 age-and gender-matched healthy controls from Beijing Tiantan Hospital,Capital Medical University between November 2023 and November 2024.All participants underwent 7T MRI with 3D T1-weighted magnetization-prepared two rapid gradient-echo(MP2RAGE)sequences for structural brain imaging.VBM analysis was performed to quantify GM,white matter,cerebrospinal fluid and total brain volumes,followed by calculations of their relative percentages.The difference in GM volume between the two groups was compared to identify brain regions with characteristic GM volume changes in migraine patients.And the correlation between these characteristic GM volume alterations and clinical scales was analyzed.Results Migraine patients exhibited significantly lower total GM volume compared to healthy controls(t=2.096,P=0.040),while no group differences were observed in white matter or cerebrospinal fluid volumes(t=0.980,0.151;P=0.330,0.880).VBM analysis revealed reduced GM volume in the left orbitofrontal cortex(t=4.301,P=0.022),left hippocampus(t=5.226,P=0.006)and left parahippocampal gyrus(t=3.960,P=0.040)in the migraine group.Negative correlations were identified between:left orbitofrontal cortex GM volume and headache duration(r=-0.506,P=0.008),left hippocampal GM volume and patient health questionnaire-9 scores(r=-0.620,P=0.003),and left parahippocampal GM volume and visual analogue scale scores(r=-0.449,P=0.019).Conclusion VBM analysis based on 7T MP2RAGE data demonstrates characteristic GM volume reductions in the left orbitofrontal cortex,left hippocampus and left parahippocampal gyrus in migraine patients,with these structural alterations significantly correlate with depressive symptoms and headache burden.The observed microstructural abnormalities may reflect underlying pathophysiological mechanisms related to pain processing,emotional regulation and long-term disease burden in migraine.

ObjectiveTo evaluate the reliability and validity of the Dampness Syndrome Scale of Chinese Medicine （DSSCM） among patients with persistent asthma， and to explore the correlation between dampness syndrome and clinical characteristics of persistent asthma. MethodsA cross-sectional survey was conducted. Basic information， examination results， DSSCM， Asthma Control Test （ACT）， Generalized Anxiety Disorder-7 （GAD-7）， and Patient Health Questionnaire-9 （PHQ-9） scores were collected from 206 patients with persistent asthma to evaluate the reliability and validity of DSSCM and to explore the correlation between dampness syndrome and clinical characteristics. ResultsThe mean score of DSSCM among 206 patients was 14.59 ± 10.53. The overall Cronbach α coefficient and Spearman-Brown split-half reliability coefficient of the scale were both greater than 0.8， and the success rate of scale convergent and discriminant validity calibration were greater than 80%. The confirmatory factor analysis showed that the χ²/df was 2.309， and the root mean square error of approximation （RMSEA） was 0.08； the root mean square residual （RMR） was 0.049， whereas the comparative fit index （CFI）， the goodness of fit index （GFI）， the adjusted goodness of fit index （AGFI）， the normed fit index （NFI） and the incremental fit index （IFI） were less than 0.9. Correlation analysis showed that DSSCM scores were positively correlated with disease duration， GAD-7 scores， and PHQ-9 scores （P＜0.05）， and negatively correlated with ACT scores （P＜0.01）. The DSSCM scores were significantly different between patients with different disease severity （H = 10.92， P = 0.01）， and the DSSCM scores of allergic patients were higher than those of non-allergic patients （Z = -4.19， P＜0.001）. ConclusionDSSCM has acceptable reliability and validity for patients with persistent asthma. The scores of DSSCM correlated with the disease duration， ACT score， GAD-7 score， PHQ-9 score， disease severity and allergic status of persistent asthmatics.

Objective:Evaluation of the effectiveness of domestic ultrapulsed thulium laser ablation of isolated porcine kidneys.Methods:Forty-two fresh porcine kidneys were taken. One porcine kidney was dissected along the sagittal plane at the renal hilum, and then dissected along the coronal plane and divided into four pieces.A total of 168 pieces of renal tissues were obtained, of which 162 pieces were selected for the domestic hyperpulsed thulium laser ablation of isolated porcine kidneys using the single-needle method and the double-needle method, respectively. The ablation was carried out with different ablation modes (single-needle and double-needle methods), ablation power (4, 5, and 6 W), ablation modes (continuous, low-energy and high-frequency mode, and high-energy and low-frequency mode), and ablation time (10, 15, and 20 s). The size of the ablation area in terms of the long diameter, the short diameter, and the thick diameter were measured and recorded. The embedded tissues were sectioned and stained with HE to study the microscopic pathological characteristics of the ablation foci. The ablation foci volume and sphericity coefficient (Φ) were calculated, and the ablation foci volume and sphericity coefficient were statistically analyzed by analytic factorial design and one-way ANOVA.Results:The gross specimen showed that the single-needle ablation foci were elliptical in shape, containing black carbonized areas and gray-white necrotic areas with clear boundaries, and the peripheral renal tissues were pink, and the ablation focus was clearly demarcated from the normal tissues. The double-needle ablation foci were a large ellipse containing two small ellipse ablation foci, and the structure was similar to that of the single-needle method. Under the light microscope, the center of the ablation focus was a "cavity-like" carbonized area, outside of which was an area of coagulation necrosis, with deepened cell staining, reduced cell volume, disorganized arrangement, loose nuclei, nuclear consolidation, and some cell nuclei were cleaved and ablated. Ablation mode ( P<0.001), ablation pattern ( P <0.001), ablation time ( P <0.001), and ablation power ( P <0.001) all significantly affected ablation focus volume. The volume of the ablation foci increased with increasing number of needle feeds, longer ablation time, higher ablation power, and with the ablation mode being continuous mode. Single-needle ablation produced the largest volume of ablation foci (259.56 mm 3) in continuous mode, ablation time of 20 s, and ablation power of 6 W. Double-needle ablation produced the largest volume of ablation foci (452.00 mm 3) in continuous mode, ablation time of 20 s, and ablation power of 6 W. The analysis of the sphericity coefficient showed that in single-needle ablation, the sphericity coefficient was the largest (Φ=0.76) under the conditions of continuous mode, ablation power of 4 W, and ablation time of 15 s. The sphericity coefficient was the smallest (Φ=0.56) under the conditions of high-energy, low-frequency mode, ablation time of 10 s, and ablation power of 6 W, and the morphology of the ablation foci were more close to ellipsoid shape. When ablated by the double-needle method, the ablation foci morphology was closer to spherical shape (Φ=0.91) under the conditions of continuous mode, ablation time of 10 s, and ablation power of 5 W. The combined main effect and interaction results showed that ablation mode ( P<0.001), ablation pattern ( P<0.001), and ablation power ( P<0.001) significantly affected the sphericity coefficient of the ablation foci, and ablation time did not affect the ablation foci morphology. Conclusions:Domestic ultrapulsed thulium laser ablates isolated porcine kidney tissues with precise effect, the tissue morphology of the unablated area is normal, the thulium laser ablated foci have a definite safe boundary. Choosing double needle method, continuous mode, ablation power 6 W for 20 s, can ablate spherical cancer foci within 1 cm in diameter, which can be used for spherical small kidney cancer ablation. Selecting the single-needle method, high-frequency, low-energy mode and ablation power of 6 W, the ablation foci were similar to the oval volume, and could be used for the ablation of oval small renal cancer. However, this study is only limited to the animal ex vivo model, which needs to be confirmed by further study.

Objective:To investigate the prevalence of thyroid nodules (TN) among people undergoing physical examination in Taiyuan City, and evaluate the impact of hyperuricemia (HUA) on the risk of TN.Methods:Using a prospective design, a total of 42 966 people who underwent routine physical examination at Shanxi Shangning Health Examination Center from October 2020 to October 2021 were selected as subjects and divided into the HUA group ( n = 7 235) and the non-HUA group ( n = 35 731) based on the serum uric acid levels. The propensity score matching (PSM) method was used to balance the confounding factors between groups, and logistic regression was used to analyze the impact of HUA on the risk of TN. Results:The total detection rate of TN in the physical examination population was 55.6% (23 907/42 966). The detection rate of TN in females [61.0% (15 011/24 618)] was higher than that in males [48.5% (8 896/18 348)], and the difference was statistically significant (χ 2 = 664.55, P < 0.001). A total of 2 438 pairs of matching data were obtained after PSM, and the distribution of confounding factors in HUA and non-HUA groups reached equilibrium (the absolute values of standardized differences < 0.10). Logistic regression analysis before PSM showed that HUA was a protective factor for the incidence of TN in general population and males [odds ratio ( OR) = 0.696, 0.817, 95% confidence interval ( CI): 0.661 - 0.732, 0.768 - 0.868], while HUA was a risk factor for the incidence of TN in females ( OR = 1.370, 95% CI: 1.192 - 1.574). After PSM, HUA was not a influencing factor for the incidence of TN in general population and males ( P > 0.05), but it was still a risk factor in females for the onset of TN ( OR = 1.373, 95% CI: 1.014 - 1.858). Conclusion:In the physical examination population in Taiyuan City, HUA is an independent risk factor for TN in females.

Objective:To explore the association between dietary patterns and the incidence of type 2 diabetes mellitus(T2DM), so as to provide insights for the prevention and management of T2DM.Methods:Participants were recruited from the " The Tianjin Chronic Inflammation and Health Cohort Study(TCLSIH)" cohort study from 2013 to 2018, who had completed the modified semiquantitative food frequency questionnaire(FFQ) and blood glucose testing( n=26 425), free of cardiovascular disease, cancer, or diabetes at baseline. The relevant information collected includes food frequency, blood glucose concentration, and other confounding factors. In this study, the correlation between dietary patterns and T2DM was tested using Cox proportional risk regression model, and the gender stratification analysis and body mass index stratification analysis of different gender groups were carried out. All statistical analysis was performed using SAS 9.3 software. Results:The age of all participants was (41.0±11.5)years, and the cumulative incidence was 3.84% for T2DM. The cumulative incidence of T2DM in male population was 5.29%, while that in female population was 2.16%. There were significant differences in the incidence of T2DM among different genders( P <0.001). The multivariable-adjusted hazard ratios( HR) and corresponding 95% CI of T2DM across the plant-based dietary pattern score were 1.09(95% CI 0.91-1.31), 0.80(95% CI 0.66-0.97), and 0.76(95% CI 0.62-0.94; Ptrend =0.010). Moreover, no statistically significant differences were observed between animal and traditional northern Chinese diets with the incidence of T2DM. Conclusions:The plant-based dietary patterns were associated with substantially lower risk of developing T2DM, and there were no significant association between animal and traditional northern Chinese dietary patterns with T2DM. Plant-based dietary patterns characterized by a variety of fruit, leeks, onions, seaweed may be beneficial to the prevention and control of T2DM.

Objective:To investigate the impact of excessive fluoride exposure on the expression profile of microRNA (miRNA) in mouse testes, and elucidate the reproductive toxicity mechanism of fluoride.Methods:A total of 24 8-week-old C57BL/6J male mice weighing (23 ± 1) g were randomly divided into a control group [0 mg/L sodium fluoride (NaF)] and a fluoride exposure group (50 mg/L NaF) using a random number table method, with 12 mice in each group. After 90 days of treatment, the mice were anesthetized and euthanized. Sperm samples were collected to assess their quantity, viability, and deformity rate. Additionally, testicular tissue was stained with hematoxylin-eosin (HE). RNA was extracted from testicular tissue, and high-throughput sequencing technology was employed to analyze the effect of fluoride on the expression profile of mouse testicular miRNA. Deferentially expressed miRNA was screened and its target genes were predicted, and functional annotation and pathway enrichment analysis were performed. Real-time fluorescence quantitative PCR (qRT-PCR) was used to verify the expression level of deferentially expressed miRNA.Results:Compared with the control group [number of sperm: (11.30 ± 2.52) × 10 6/ml; viability rate: (90.07 ± 4.34)%; deformity rate: (15.49 ± 3.25)%], the number of sperm of mice exposed to fluoride [(9.01 ± 2.25) × 10 6/ml] and the viability rate [(84.34 ± 4.21)%] decreased ( P = 0.041, 0.003), while deformity rate [(22.36 ± 6.51)%] increased ( P = 0.003). Furthermore, in the fluoride exposure group, the interstitial distance of testis increased, the number of sperm in the spermatogenic tubule decreased, and the cell arrangement was disordered. Through sequencing, 34 deferentially expressed miRNAs were identified in the testes of mice exposed to fluoride. According to qRT-PCR verification, compared with the control group, the expression levels of mmu-miR-29b-1-5p ( P < 0.001), mmu-miR-196a-5p ( P = 0.002), and mmu-miR-196b-5p ( P = 0.031) in the testes of mice exposed to fluoride were significantly increased, and the expression levels of mmu-let-7a-2-3p ( P < 0.001) and mmu-miR-466n-3p ( P = 0.018) were significantly decreased, consistent with the sequencing results. By KEGG enrichment of deferentially expressed miRNA target genes, it was found that fluoride exposure could change the axon guidance signal pathway, olfactory transduction pathway, neuroactive ligand-receptor interaction pathway, and lysosome signal pathway, etc., in mouse testes. Conclusions:Fluoride exposure may induce testicular injury by altering the expression profile of miRNA in the testes and by mediating the post-transcriptional regulatory signal pathway. Testicular miRNA may be a potential biomarker of fluoride reproductive toxicity, which may provide a new idea and perspective for exploring the mechanism of fluoride poisoning.