ObjectiveTo characterize the quality differences among different germplasm and introduced varieties of Bupleurum scorzonerifolium roots（BSR）， and explore the underlying molecular mechanisms， providing a basis for high-quality production and quality control. MethodsWild BSR from Yulin（YLW） served as the quality reference， we conducted comparative analysis among YLW， locally domesticated wild germplasm in Yulin（YLC3）， Daqing germplasm introduced and cultivated in Yulin（YLDQC3）， and locally cultivated germplasm in Daqing（DQC3）. A combination of traditional pharmacognostic methods and modern multi-omics analyses was employed， including macroscopic traits（appearance， odor）， microscopic features（proportions of cork， phloem， xylem）， cell wall component contents（hemicellulose， cellulose， lignin）， carbohydrate contents（starch， water-soluble polysaccharides）， marker compound contents（ethanol-soluble extracts， total saponins， liposoluble extracts， and saikosaponins A， B₂， C， D）， metabolomics， and transcriptomics， in order to systematically characterize quality differences and investigate molecular mechanisms among these samples. ResultsMacroscopically， Yulin-produced BSR（YLW， YLC3， YLDQC3） exhibited significantly greater weight， length， and upper and middle diameters than Daqing-produced BSR（DQC3）. Odor-wise， YLW and YLC3 had a a fragrance taste， YLDQC3 had a rancid oil odor， and DQC3 had a sweet and fragrant taste. Microscopically， Yulin germplasm（YLW， YLC3） and Daqing germplasm（YLDQC3， DQC3） shared similar structural features， respectively. However， Yulin germplasm showed significantly higher proportions of cork and phloem， as well as stronger xylem vessel staining intensity compared to Daqing germplasm. Regarding various component contents， Yulin germplasm contained significantly higher levels of ethanol-soluble extracts， total saponins， and saikosaponins A， B₂， C， D， while Daqing germplasm had significantly higher levels of hemicellulose， starch， and liposoluble extracts. After introduction to Yulin， the Daqing germplasm（YLDQC3） showed increased starch， water-soluble polysaccharides and liposoluble extracts contents， decreased cell wall component content， but no significant difference in other component contents. Metabolomics revealed that saponins and terpenes accumulated significantly in Yulin germplasm， while alcohols and aldehydes accumulated predominantly in Daqing germplasm. Transcriptomics indicated similar gene expression patterns within the same germplasm but specificity between different germplasms. Integrative metabolomic-transcriptomic analysis identified 145 potential key genes associated with the saikosaponin biosynthesis pathway， including one acetyl-coenzyme A（CoA） acetyltransferase gene（ACAT）， one 3-hydroxy-3-methylglutaryl-coenzyme A synthase gene（HMGS）， two hydroxymethylglutaryl-CoA（HMG-CoA） reductase genes（HMG）， one phosphomevalonate kinase gene（PMK）， one 1-deoxy-D-xylose-5-phosphate synthase gene（CLA）， one hydroxymethylbuten-1-aldol synthase gene（HDR）， two farnesyl pyrophosphate synthase genes（FPPS）， one squalene synthase gene（SQS）， one β-amyrin synthase gene（BAS）， 102 cytochrome P450（CYP450） gene family members， and 32 uridine diphosphate-glucuronosyltransferase（UGT） gene family members. ConclusionAmong the three cultivated types， YLC3 most closely resembles YLW in appearance， microscopic features， contents of major bioactive constituents， metabolomic and transcriptomic profiles. Yulin germplasm exhibits superior saponin synthesis capability compared to Daqing germplasm， and Yulin region is more suitable for the growth of B. scorzonerifolium. Based on these findings， it is recommended that artificial cultivation in northern Shaanxi and similar regions utilize the local Yulin germplasm source cultivated for at least three years.

ObjectiveBased on the traditional quality evaluation methods summarized in previous dynasties， this paper systematically contrasted the quality differences between wild Polygalae Radix（WPR） and cultivated Polygalae Radix（CPR） from the aspects of character， microscope and chemical composition by modern scientific and technological means， providing a basis for high-quality production and quality control. MethodsCPR and local WPR in Yulin city， Shaanxi province from 1 to 6 years were collected， and a systematic comparative analysis was conducted using traditional pharmacognosy research methods combined with modern multi-omics analysis techniques， including character traits（length， weight， diameter）， cross-sectional microscopic features（proportions of cork， phloem， xylem， etc）， cell wall component content（hemicellulose， cellulose， lignin）， extracts content（water-soluble extract and alcohol-soluble extract）， carbohydrate content（starch， water-soluble polysaccharides）， contents of total flavonoids， total saponins and specific marker compounds（3，6′-disinapoyl sucrose， polygalaxanthone Ⅲ， tenuifoliside A， tenuifoliside C， sibiricose A₅ and A₆） and other indexes. Ultra-high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS） was employed to conduct comparative analysis of secondary metabolites in WPR and CPR， and multivariate statistical analysis such as principal component analysis（PCA） and orthogonal partial least squares-discriminant analysis（OPLS-DA） were combined to screen the key differential components of them. ResultsIn terms of appearance， there were significant differences between WPR and CPR. The characteristics of WPR conformed to the "thick wrinkles on the epidermis" recorded in ancient books， featuring a wrinkled surface and grayish-brown appearance. However， CPR had a finer texture and a yellowish white appearance， with weight， length， and diameter increasing with longer cultivation periods. In terms of microscopy， WPR exhibited a thick cork layer with fissures in the phloem， whereas CPR had a thinner cork layer with uniformly arranged cork cells. Younger PR specimens showed numerous phloem fissures in cross-sections， while older specimens display progressively denser arrangements of phloem parenchyma cells. In terms of the contents of various major components， the contents of water-soluble extract， starch and total saponins in WPR were inversely proportional to the root diameter， while the contents of water-soluble extract， water-soluble polysaccharides and total saponins in CPR decreased with the increase of planting years. The content of xanthones in WPR was significantly higher than that of CPR， while the contents of other major components showed no significant change pattern. Among the six indicator components， the average content of sibiricose A₅ in WPR was significantly higher than that of CPR， followed by slightly higher content of tenuifoliside A. In CPR， the relative content of 3，6′-disinapoyl sucrose and tenuifoliside A was the highest. The former showed an increase in volatility with increasing cultivation years， while the latter showed a decrease in volatility. The results of differential compound analysis based on UPLC-Q-TOF-MS showed that there were significant differences in metabolites between WPR and CPR samples. Among them， the seven compounds with the largest differences among WPR samples of different thicknesses were polygalasaponins， and for CPR with different planting years， the main differential compounds were oligosaccharide esters. ConclusionThere are differences between WPR and CPR in character， microscopic structure and chemical composition， and some components are inversely proportional with the increase of diameter and cultivation duration due to the distribution characteristics. However， the longer the cultivation years of PR， the closer it is to the "thick wrinkles on the epidermis" of WPR， which has been respected by generations. It is suggested that this traditional character combined with modern component contents should be used as the index of artificial cultivation and quality control of PR.

Objective: The cross sectional study aimed to identify predominant co-occurrence patterns among six common mental health issues in college students, so as to provide empirical basis for designing targeted interventions. Methods: From October 2024, a total of 9 837 students from 4 universities in Xiangtan City, Hunan Province, participated in the current study by multistage random cluster sampling method. Participants completed self report measures, including the Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder 7 item Scale (GAD-7), Young s Internet Addiction Diagnostic Questionnaire, the Adolescent Insomnia Symptom Self rating Scale, the Ottawa Self injury Inventory, and the Brief Community Assessment of Psychic Experiences Questionnaire. Demographic and co-occurrence characteristics were first compared using Chi square or trend Chi-square tests, followed by application of the Apriori algorithm to mine association rules for primary co-occurrence patterns. Results: The detection rate of co-occuring the common mental health issues was 46.44%. The detection rate was significantly higher in female than in male students (50.42%, 43.61%; χ 2=44.46) and in students from rural versus urban areas (47.22%, 44.60%; χ 2=5.67) (both P <0.05). Significant differences were observed among freshmen, sophomores, juniors, and seniors (46.63%, 48.35%, 45.05% , 43.66%, respectively; χ 2=9.22, P <0.05), although no statistically significant trend was detected ( χ 2 trend =3.75, P = 0.05 ). Association rule mining identified “anxiety + depression” “anxiety + psychotic experiences + depression” and “anxiety + sleep disorder + depression” as the combinations with the highest support. In addition, “anxiety+depression+Internet addiction+psychotic experiences =>sleep disorder (>= refered to the occurrence of the latter item under the condition that the former item occurs)” and “anxiety + depression+Internet addiction=>sleep disorder” were combinations with relatively high confidence. Conclusions Co-occurrence of these mental health issues among college students is high and exhibits diverse patterns. Strategies to address this burden should prioritize integrated interventions that target these specific combinations of factors.

ObjectiveTo address the limitations of the current quality standard for Polygalae Radix（PR）， which relies on a single component for quality assessment and struggles to holistically control its intrinsic quality， by constructing a comprehensive quality evaluation system integrating "macro-characterization of chemical profile， synchronous quantification of multiple index components， and quantitative analysis of multi-components by single marker（QAMS） for key component groups". This study aims to facilitate the scientific revision of the quality standard for PR. MethodsHigh performance liquid chromatography（HPLC） characteristic chromatograms were established for 11 batches of PR medicinal materials（YZ）， 10 batches of PR decoction pieces（YP）， and 10 batches of licorice-processed PR decoction pieces（ZYZ）， followed by similarity evaluation and identification of common peaks. HPLC-QAMS was developed for xanthones（sibiricaxanthone B， polygalaxanthone Ⅺ， polygalaxanthone Ⅲ） in the characteristic chromatograms. Simultaneously， the external standard method（ESM） was used to determine the contents of the corresponding xanthones and 3，6'-disinapoyl sucrose in YZ， YP， and ZYZ， followed by multivariate statistical analysis and Spearman correlation analysis. ResultsThe similarity between the characteristic chromatograms of 31 batches of PR samples and the reference chromatogram was>0.9. A total of 13 common peaks were identified， and 10 of these peaks were characterized through reference standard comparison. The successfully constructed QAMS method showed that the relative correction factors（RCFs） of sibiricaxanthone B and polygalaxanthone Ⅺ to polygalaxanthone Ⅲ were 0.76 and 0.88， and their relative retention times（RRTs） were 0.85 and 0.97， respectively. The results calculated by the QAMS method showed no significant difference from those obtained by the ESM. According to the limit standard for polygalaxanthone Ⅲ in the 2020 edition of the Pharmacopoeia of the People's Republic of China（hereinafter referred to as the Chinese Pharmacopoeia）， the pass rate of 31 batches of samples was only 19.35%. Multivariate statistical analysis indicated certain compositional differences between different batches of YZ and YP， as well as between YP and ZYZ， with 3，6'-disinapoyl sucrose identified as the main differentiating component. Furthermore， correlation analysis revealed that the content of polygalaxanthone Ⅲ was positively correlated with the contents of sibiricaxanthone B and polygalaxanthone Ⅺ， but showed no association with the content of 3，6'-disinapoyl sucrose. ConclusionIt is recommended that the content limit for polygalaxanthone Ⅲ in YZ，YP and ZYZ be revised to not less than 0.07%， or the total content of polygalaxanthone Ⅲ， sibiricaxanthone B and polygalaxanthone Ⅺ be not less than 0.18%. The newly established triple quality control model of "holistic control via characteristic chromatograms， precise quantification of oligosaccharide esters， and efficient detection of xanthones by QAMS" provides a systematic and precise solution for quality evaluation of PR and similar Chinese herbal medicines.

Immune checkpoint inhibitors (ICIs) are widely used in the treatment of malignant tumors, and their related immune-related adverse events (irAEs) have attracted increasing attention. This study reports the diagnosis and treatment process of a case of immune cystitis in a patient with hepatobiliary tract malignant tumor after treatment with pembrolizumab. The patient was admitted to the hospital due to frequent urination, urgency of urination and dysuria for 1 month. Previous repeated anti-infection treatments were ineffective. Combined with medical history, laboratory tests, imaging findings, cystoscopy and pathological results, the patient was clinically diagnosed with ICIs-associated immune cystitis (Pembrolizumab) ultimately. The patient's symptoms significantly improved after treatment with glucocorticoids. This case reindicates that clinicians need to improve awareness of ICI-related urinary system irAEs. Early identification and timely intervention can significantly improve patient prognosis.

ObjectiveTo investigate the molecular mechanisms related to angiogenesis during the development and progression of diabetic retinopathy （DR）. MethodsAngiogenesis-related genes were obtained from the Gencard website and intersected with differentially expressed genes from DR datasets （GSE60436 and GSE94019）. Functional enrichment and protein-protein interaction （PPI） networks were then used to screen candidate genes and evaluate their diagnostic value. Gene set enrichment analysis （GSEA） was used to explore potential pathways underlying candidate genes， and immune infiltration analysis revealed associations between candidate genes and immune cells. Cellular experiments were conducted to validate the role of fibronectin 1 （FN1） in human retinal microvascular endothelial cells （HRMECs） under high glucose （HG） conditions. ResultsA total of 237 differentially expressed genes related to angiogenesis were identified， enriched in pathways such as phosphoinositide 3-kinase/protein kinase B signaling pathway （PI3K-Akt）， tumor suppressor protein 53 （P53）， tumor necrosis factor （TNF）， and Janus kinase （JAK）/signal transducer and activator of transcription signaling pathway （STAT）. Among them， collagen type I alpha 1 chain （COL1A1）， COL1A2， FN1， TNF， and tumor protein p53 （TP53） were key genes with high diagnostic value. GSEA indicated that these genes were involved in multiple signaling pathways， including P53. CIBERSORTx analysis revealed significant associations with the infiltration of multiple immune cells. HG treatment led to the upregulation of FN1. In HG-induced HRMECs， compared with the si-NC control group， si-FN1 significantly reduced cell proliferation， migration， and tube formation， while P53 protein expression was increased. ConclusionThis study reveals the important role of FN1 in angiogenesis in DR and suggests that it may be a potential diagnostic and therapeutic target.

Objective To evaluate the effect of low-dose ¹⁸F-fluorodeoxyglucose (FDG) injection on image quality in pediatric patients, calculate the whole-body effective dose and absorbed doses to critical organs, and provide a reference for clinical protection in pediatric low-dose positron emission tomography/computed tomography (PET/CT) examination. Methods A total of 67 pediatric patients aged 4-14 years who underwent ¹⁸F-FDG whole-body PET/CT imaging in the Department of Nuclear Medicine, The First Affiliated Hospital of Shandong First Medical University between January 2024 and December 2025 were enrolled in a retrospective study. According to the injected ¹⁸F-FDG dose, patients were divided into a full-dose group (37 cases, 2.96-3.7 MBq/kg, PET acquisition duration of 10 min) and a low-dose group (30 cases, 1.85-2.4 MBq/kg, PET acquisition duration of 15 min). All scans were performed using a uEXPLORER PET/CT scanner. The standardized uptake value, standard deviation, and signal-to-noise ratio were measured for the liver and mediastinal blood pool. Image quality was compared between the two groups. The PET effective dose was calculated based on body mass index, and the total effective dose was obtained by combining PET effective dose with CT effective dose. The doses to critical organs were calculated according to ICRP Publication 128. Statistical analysis was performed using SPSS 26.0 and Prism 9.0 software. Differences were compared between groups. Results There were no significant differences in age, sex, weight, height, or body mass index between the two groups (P>0.05), while the injected dose showed a significant difference (P<0.001). In terms of image quality, there were no significant differences in standardized uptake value, standard deviation, and signal-to-noise ratio between the two groups. In terms of radiation dose, compared with the full-dose group, the low-dose group showed a 35.13% reduction in PET effective dose and a 15.22% reduction in total effective dose (P<0.05), whereas the CT effective dose was reduced by 2.4% and the difference was not significant (P=0.0892). The doses to critical organs (gonads, breasts, thyroid, red bone marrow, lungs) in the low-dose group were significantly lower than those in the full-dose group (P<0.01). Conclusion Under the premise of meeting clinical diagnostic requirements, low-dose ¹⁸F-FDG whole-body PET/CT imaging in pediatric patients can reduce the overall radiation exposure by 15%, and decrease the doses to critical organs, including the gonads, by more than 20%.

AIM:To explore the toxicological mechanisms of benzalkonium chloride(BAC)as a preservative in ophthalmic preparations leading to corneal injury in dry eye.METHODS:Network toxicology was employed to obtain the chemical structure of BAC, its toxic targets, and targets associated with dry eye-related corneal injury from databases including PubChem, CTD, ChEMBL, and STITCH. The protein-protein interaction(PPI)networks were constructed using the STRING database to screen key toxicity targets. Gene ontology(GO)functional annotation and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analyses were performed to elucidate the potential biological processes and signaling pathways affected by BAC. Furthermore, molecular docking techniques were employed to validate the binding affinity of BAC to its key targets(IL-6, IL-1β, TNF, and EGF).RESULTS:BAC had a toxicity grade of 4 and exhibited significant eye irritation. A total of 85 common targets of BAC and dry eye corneal damage were screened out, of which 49 were key toxic targets, including TNF, IL-6, TP53, IL-1β, BCL2, etc. KEGG enrichment analysis showed that BAC mainly acted on 7 corneal injury pathways closely associated with corneal injury, such as IL-17, TNF, NF-κB, JAK-STAT, PI3K-Akt, Rap1, and MAPK. The results of molecular docking showed that BAC had stable binding ability to IL-6, IL-1β, TNF, EGF, and other targets(binding energy <0).CONCLUSION:BAC may induce corneal damage in dry eye through multi-target and multi-pathway mechanisms, involving processes such as inflammatory response, apoptosis, disruption of tear film stability, and delayed corneal repair, which suggests that long-term use of ophthalmic preparations containing BAC may aggravate ocular surface damage.

Objective To evaluate the effect of low-dose ¹⁸F-fluorodeoxyglucose (FDG) injection on image quality in pediatric patients, calculate the whole-body effective dose and absorbed doses to critical organs, and provide a reference for clinical protection in pediatric low-dose positron emission tomography/computed tomography (PET/CT) examination. Methods A total of 67 pediatric patients aged 4-14 years who underwent ¹⁸F-FDG whole-body PET/CT imaging in the Department of Nuclear Medicine, The First Affiliated Hospital of Shandong First Medical University between January 2024 and December 2025 were enrolled in a retrospective study. According to the injected ¹⁸F-FDG dose, patients were divided into a full-dose group (37 cases, 2.96-3.7 MBq/kg, PET acquisition duration of 10 min) and a low-dose group (30 cases, 1.85-2.4 MBq/kg, PET acquisition duration of 15 min). All scans were performed using a uEXPLORER PET/CT scanner. The standardized uptake value, standard deviation, and signal-to-noise ratio were measured for the liver and mediastinal blood pool. Image quality was compared between the two groups. The PET effective dose was calculated based on body mass index, and the total effective dose was obtained by combining PET effective dose with CT effective dose. The doses to critical organs were calculated according to ICRP Publication 128. Statistical analysis was performed using SPSS 26.0 and Prism 9.0 software. Differences were compared between groups. Results There were no significant differences in age, sex, weight, height, or body mass index between the two groups (P>0.05), while the injected dose showed a significant difference (P<0.001). In terms of image quality, there were no significant differences in standardized uptake value, standard deviation, and signal-to-noise ratio between the two groups. In terms of radiation dose, compared with the full-dose group, the low-dose group showed a 35.13% reduction in PET effective dose and a 15.22% reduction in total effective dose (P<0.05), whereas the CT effective dose was reduced by 2.4% and the difference was not significant (P=0.0892). The doses to critical organs (gonads, breasts, thyroid, red bone marrow, lungs) in the low-dose group were significantly lower than those in the full-dose group (P<0.01). Conclusion Under the premise of meeting clinical diagnostic requirements, low-dose ¹⁸F-FDG whole-body PET/CT imaging in pediatric patients can reduce the overall radiation exposure by 15%, and decrease the doses to critical organs, including the gonads, by more than 20%.

Objective To evaluate the effect of low-dose ¹⁸F-fluorodeoxyglucose (FDG) injection on image quality in pediatric patients, calculate the whole-body effective dose and absorbed doses to critical organs, and provide a reference for clinical protection in pediatric low-dose positron emission tomography/computed tomography (PET/CT) examination. Methods A total of 67 pediatric patients aged 4-14 years who underwent ¹⁸F-FDG whole-body PET/CT imaging in the Department of Nuclear Medicine, The First Affiliated Hospital of Shandong First Medical University between January 2024 and December 2025 were enrolled in a retrospective study. According to the injected ¹⁸F-FDG dose, patients were divided into a full-dose group (37 cases, 2.96-3.7 MBq/kg, PET acquisition duration of 10 min) and a low-dose group (30 cases, 1.85-2.4 MBq/kg, PET acquisition duration of 15 min). All scans were performed using a uEXPLORER PET/CT scanner. The standardized uptake value, standard deviation, and signal-to-noise ratio were measured for the liver and mediastinal blood pool. Image quality was compared between the two groups. The PET effective dose was calculated based on body mass index, and the total effective dose was obtained by combining PET effective dose with CT effective dose. The doses to critical organs were calculated according to ICRP Publication 128. Statistical analysis was performed using SPSS 26.0 and Prism 9.0 software. Differences were compared between groups. Results There were no significant differences in age, sex, weight, height, or body mass index between the two groups (P>0.05), while the injected dose showed a significant difference (P<0.001). In terms of image quality, there were no significant differences in standardized uptake value, standard deviation, and signal-to-noise ratio between the two groups. In terms of radiation dose, compared with the full-dose group, the low-dose group showed a 35.13% reduction in PET effective dose and a 15.22% reduction in total effective dose (P<0.05), whereas the CT effective dose was reduced by 2.4% and the difference was not significant (P=0.0892). The doses to critical organs (gonads, breasts, thyroid, red bone marrow, lungs) in the low-dose group were significantly lower than those in the full-dose group (P<0.01). Conclusion Under the premise of meeting clinical diagnostic requirements, low-dose ¹⁸F-FDG whole-body PET/CT imaging in pediatric patients can reduce the overall radiation exposure by 15%, and decrease the doses to critical organs, including the gonads, by more than 20%.