Based on the pharmacokinetics theory, this study investigated the pharmacokinetic characteristics of albiflorin, paeoniflorin, wogonoside, and wogonin in normal and febrile rats and summarized absorption and elimination rules of Dayuanyin in them to provide reference for further development and clinical application of Dayuanyin. Blood samples were taken from the fundus venous plexus of normal and model rats after intragastric administration of Dayuanyin at different time points. The concentration of each substance in blood was determined by ultra performance liquid chromatography-triple quadrupole mass spectrometry(UPLC-MS/MS) technique at different time points. DAS 2.0, a piece of pharmacokinetics software, was used to calculate the pharmacokinetic parameters of each component. The results show that the 4 components had good linear relationship in their respective ranges, and the results of methodological investigation met the requirements. The pharmacokinetic parameters of C_(max), T_(max), t_(1/2), AUC_(0-t), AUC_(0-∞), and MRT_(0-t) were calculated by the DAS 2.0 non-compartmental model. Compared with those in the normal group, C_(max) and AUC_(0-t) of the 4 components in the model group were significantly increased. There were significant differences in the pharmacokinetic characteristics between the normal and model groups, suggesting that the absorption and elimination of Dayuanyin may be affected by the changes of internal environment of the body in different physiological states.
Animals ; Rats ; Drugs, Chinese Herbal/administration & dosage* ; Male ; Rats, Sprague-Dawley ; Fever/metabolism* ; Tandem Mass Spectrometry ; Chromatography, High Pressure Liquid ; Glucosides/pharmacokinetics* ; Monoterpenes

This study explored the drying kinetics of Salviae Miltiorrhizae Radix et Rhizoma(SM), established the suitable models simulating the drying kinetics, and then analyzed the dynamic changes of active components during the drying processes with different methods, aiming to provide a basis for the establishment of suitable drying methods and the quality control of SM. The drying kinetics were studied based on the drying curve, drying rate, moisture effective diffusion coefficient, and drying activation energy, and the appropriate drying kinetics model of SM was established. The drying performance of different methods, such as hot air drying, infrared drying, and microwave drying of SM was evaluated, and the changes in the content of 10 salvianolic acids and 6 tanshinones during drying were analyzed by UPLC-TQ-MS. The Technique for Order Preference by Similarity to an Ideal Solution(TOPSIS) was employed to evaluate the quality of SM dried with different methods. The results showed that the drying rate and moisture effective diffusion coefficient of SM increased with the rise in drying temperature, and the maximum drying rates of different methods were in the order of microwave drying > infrared drying > hot air drying, slice > whole root. The drying rate decreased with the rise in temperature and the extension of drying time. The activation energy of hot air drying was higher than that of infrared drying in SM. The most suitable model for simulating the drying process of SM was the Page model. The TOPSIS results suggested infrared drying at 50 ℃ was the optimal drying method for SM. During the drying process, the content of salvianolic acids increased in different degrees with the loss of moisture, among which salvianolic acid B showed the largest increase of 44 times compared with that in the fresh medicinal material. Tanshinones also existed in the fresh herb of SM, and the content of tanshinone Ⅱ_A increased by 3 times after drying. The results provided a basis for the establishment of suitable drying methods and the quality control of SM.
Salvia miltiorrhiza/chemistry* ; Desiccation/methods* ; Drugs, Chinese Herbal/chemistry* ; Rhizome/chemistry* ; Kinetics ; Quality Control ; Abietanes

Based on the ultra performance liquid chromatography-quadrupole Exactive Orbitrap mass spectrometry(UPLC-Q-Exactive Orbitrap-MS) technology, combined with related literature, databases, and reference material information, this study qualitatively analyzed the components of Dayuanyin in the tissue of rats after gavage and employed molecular docking technology to predict the rationality of the mechanism behind the antipyretic effect of the in vivo components in Dayuanyin. A total of 21, 26, 20, 21, 14, and 31 prototype components and 3, 16, 3, 7, 5, and 24 metabolites were identified from the heart, liver, spleen, lung, kidney, and hypothalamus of the rats, respectively, and the binding ability of key components and targets was further verified by molecular docking. The results showed that all components had good binding ability with targets. The established UPLC-Q-Exactive Orbitrap-MS could effectively and quickly identify the Dayuanyin components distributed in tissue and preliminarily identify their metabolites. Many components were identified in the hypothalamus, which suggested that the components delivered to the brain should be focused on in the study on Dayuanyin in the treatment of febrile diseases. The molecular docking technology was used to predict the rationality of the mechanism behind its antipyretic effect, which lays the foundation for the clarification of the material basis and action mechanism of Dayuanyin, the development of new preparations, and the prediction of quality markers.
Animals ; Drugs, Chinese Herbal/administration & dosage* ; Rats ; Molecular Docking Simulation ; Male ; Antipyretics/metabolism* ; Rats, Sprague-Dawley ; Tissue Distribution ; Mass Spectrometry ; Chromatography, High Pressure Liquid ; Hypothalamus/metabolism*

This study aimed to characterize and identify the non-volatile components in aqueous and ethanolic extracts of the stems and leaves of Rhododendron tomentosum by using sensitive and efficient ultra-performance liquid chromatography-quadrupole-time of flight mass spectrometry(UHPLC-Q-TOF-MS) combined with a self-built information database. By comparing with reference compounds, analyzing fragment ion information, searching relevant literature, and using a self-built information database, 118 compounds were identified from the aqueous and ethanolic extracts of R. tomentosum, including 35 flavonoid glycosides, 15 phenolic glycosides, 12 flavonoids, 7 phenolic acids, 7 phenylethanol glycosides, 6 tannins, 6 phospholipids, 5 coumarins, 5 monoterpene glycosides, 6 triterpenes, 3 fatty acids, and 11 other types of compounds. Among them, 102 compounds were reported in R. tomentosum for the first time, and 36 compounds were identified by comparing them with reference compounds. The chemical components in the ethanolic and aqueous extracts of R. tomentosum leaves and stems showed slight differences, with 84 common chemical components accounting for 71.2% of the total 118 compounds. This study systematically characterized and identified the non-volatile chemical components in the ethanolic and aqueous extracts of R. tomentosum for the first time. The findings provide a reference for active ingredient research, quality control, and product development of R. tomentosum.
Rhododendron/chemistry* ; Chromatography, High Pressure Liquid/methods* ; Drugs, Chinese Herbal/chemistry* ; Mass Spectrometry/methods* ; Plant Leaves/chemistry*

BACKGROUND AND OBJECTIVE: Social anxiety arising from intensive social media usage (SMU) among adolescents and youth has gained extensive attention in recent years due to its negative influence on mental health and academic performance. In spite of that, there is a dearth regarding the etiology of SMU-related social anxiety. This study aims to further clarify the influence of introversion personality on SMU-related social anxiety and the mechanism underlying such an association and provide a new perspective for developing effective intervention strategies for the highly prevailing SMU-related anxiety among Chinese college students. METHODS: A cohort of 979 college students (266 males and 713 females) aged 20.90 ± 1.91 years was enrolled in this cross-sectional study. Four measures including the "extroversion" domain of Eysenck Personality Questionnaire Revised, Short Scale (EPQ-R-S E), Interaction Anxiousness Scale (IAS), Mobile Phone Addiction Index (MPAI), and Social Anxiety Scale for Social Media Users (SAS-SMU) were used to evaluate the influence of introversion personality on SMU-related social anxiety that was potentially mediated sequentially by interaction anxiousness and mobile phone addiction. Hayes PROCESS was used for correlation and mediation analysis. RESULTS: Interaction anxiousness (indirect effect = -1.331, 95% CI : -1.559 - -1.122) partially mediated the association between introversion personality and SMU-related social anxiety. Besides, a sequential mediation of interaction anxiousness and mobile phone addiction in the link between introversion personality and SMU-related social anxiety was revealed (indirect effect = -0.308, 95% CI : -0.404 - -0.220). No significant mediating effect was found with mobile phone addiction in the association between introversion personality and SMU-related social anxiety. CONCLUSION: Targeting interaction anxiousness and mobile phone addiction may represent an efficient strategy alleviating SMU-related social anxiety among Chinese college students with introversion personality.
Humans ; Male ; Female ; Social Media ; Students/psychology* ; Anxiety/psychology* ; Young Adult ; Cross-Sectional Studies ; Universities ; Behavior, Addictive/psychology* ; Cell Phone ; Adolescent ; Introversion, Psychological ; China ; Surveys and Questionnaires ; Internet Addiction Disorder/psychology*

The patient was a boy aged 1 year and 9 months who presented with 46,XY disorder of sex development (DSD), with severe undermasculinization of the external genitalia. Laboratory tests and ultrasound examinations showed normal functions of Leydig cells and Sertoli cells in the testes. Genetic testing revealed a novel pathogenic heterozygous variant, c.1186dupA (p.T396Nfs*17), in the PPP1R12A gene. Thirteen cases of PPP1R12A gene variants have been reported previously. These variants may cause isolated involvement of the genitourinary or neurological systems, or affect other systems/organs including the digestive tract, eyes, heart, etc. Patients with DSD typically present with a 46,XY karyotype and variable degrees of undermasculinization involving the external genitalia, gonads, and reproductive tract. This article reports a child with 46,XY DSD accompanied by growth retardation caused by a heterozygous variant in the PPP1R12A gene, which expands the clinical disease spectrum associated with PPP1R12A gene variants.
Humans ; Male ; Infant ; Disorder of Sex Development, 46,XY/etiology* ; Protein Phosphatase 1/genetics*

OBJECTIVE: To explore the role of semaphorin 4D (Sema4D) in immunoglobulin A (IgA) -mediated immune abnormalities in B lymphocytes of pediatric Henoch-Schonlein purpura (HSP). METHODS: One hundred HSP children admitted to Hengshui People's Hospital from January 2022 to January 2023 were selected as HSP group, and one hundred healthy children as control group. Sema4D expression was detected, and the relationship between Sema4D expression in children's serum and skin lesions and clinical characteristics of children was analyzed. Sema4D expression on the surface of lymphocytes of HSP children was detected. Different concentrations of human recombinant Sema4D protein was used to stimulate peripheral blood mononuclear cells in HSP children in vitro. The expression level of IgA in the supernatant was detected to verify whether Sema4D mediates immune abnormalities through IgA secreted by B lymphocytes. RESULTS: The Sema4D level in the HSP group was significantly higher than that in the control group (P <0.001). Sema4D level in HSP children with severe, renal involvement, and joint involvement was higher than those with mild to moderate disease, and no renal or joint involvement (all P <0.001). Compared with control group, IgA level, CD8 ⁺ T lymphocyte proportion, and CD19 ⁺ B lymphocyte proportion in the HSP group were significantly higher but CD4 ⁺ T lymphocyte proportion was lower (all P <0.001). The expression levels of Sema4D on the surface of CD4 ⁺ T lymphocytes, CD8 ⁺ T lymphocytes, and CD19 ⁺ B lymphocytes in the HSP group were significantly higher than those in the control group (all P <0.001). With the increase of human recombinant Sema4D protein concentration, the level of IgA expression in HSP children gradually increased (P <0.05). Correlation analysis showed that Sema4D was significantly positively correlated with IgA (r =0.667). CONCLUSION HSP children show high expression of Sema4D, especially on the surface of T and B lymphocytes. The shedding of Sema4D from membrane surface may stimulate B lymphocytes to secrete IgA by binding to CD72, leading to immune abnormalities.
Humans ; IgA Vasculitis/immunology* ; Semaphorins/metabolism* ; B-Lymphocytes/metabolism* ; Immunoglobulin A/immunology* ; Child ; Antigens, CD/metabolism* ; Male ; Female ; Child, Preschool

BACKGROUND: Lung cancer is one of the most common malignant tumors worldwide and a major cause of cancer-related deaths. Early-stage lung cancer is often manifested as pulmonary nodules, and accurate assessment of the malignancy risk is crucial for prolonging survival and avoiding overtreatment. This study aims to construct a model based on image feature parameters automatically extracted by artificial intelligence (AI) to evaluate its effectiveness in predicting the malignancy of part-solid nodule (PSN). METHODS: This retrospective study analyzed 229 PSN from 222 patients who underwent pulmonary nodule resection at Lanzhou University Second Hospital between October 2020 and February 2025. According to pathological results, 45 cases of benign lesions and precursor glandular lesion were categorized into the non-malignant group, and 184 cases of pulmonary malignancies were categorized into the malignant group. All patients underwent preoperative chest computed tomography (CT), and AI software was used to extract imaging feature parameters. Univariate analysis was used to screen significant variables; variance inflation factor (VIF) was calculated to exclude highly collinear variables, and LASSO regression was further applied to identify key features. Multivariate Logistic regression was used to determine independent risk factors. Based on the selected variables, five models were constructed: Logistic regression, random forest, XGBoost, LightGBM, and support vector machine (SVM). Receiver operating characteristic (ROC) curves were used to assess the performance of the models. RESULTS: The independent risk factors for the malignancy of PSN include roughness (ngtdm), dependence variance (gldm), and short run low gray-level emphasis (glrlm). Logistic regression achieved area under the curves ( AUCs) of 0.86 and 0.89 in the training and testing sets, respectively, showing good performance. XGBoost had AUCs of 0.78 and 0.77, respectively, demonstrating relatively balanced performance, but with lower accuracy. SVM showed an AUC of 0.93 in the training set, which decreased to 0.80 in the testing set, indicating overfitting. LightGBM performed excellently in the training set with an AUC of 0.94, but its performance declined in the testing set, with an AUC of 0.88. In contrast, random forest demonstrated stable performance in both the training and testing sets, with AUCs of 0.89 and 0.91, respectively, exhibiting high stability and excellent generalizability. CONCLUSIONS The random forest model constructed based on independent risk factors demonstrated the best performance in predicting the malignancy of PSN and could provide effective auxiliary predictions for clinicians, supporting individualized treatment decisions.
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Humans ; Male ; Female ; Lung Neoplasms/pathology* ; Middle Aged ; Retrospective Studies ; Artificial Intelligence ; Aged ; Tomography, X-Ray Computed ; Adult ; Solitary Pulmonary Nodule/diagnostic imaging* ; ROC Curve

OBJECTIVE: To explore the mechanism of colon dialysis with Yishen Decoction (YS) in improving the autophagy disorder of intestinal epithelial cells in chronic renal failure (CRF) in vivo and in vitro. METHODS: Thirty male SD rats were randomly divided into normal, CRF, and colonic dialysis with YS groups by a random number table method (n=10). The CRF model was established by orally gavage of adenine 200 mg/(kg•d) for 4 weeks. CRF rats in the YS group were treated with colonic dialysis using YS 20 g/(kg•d) for 14 consecutive days. The serum creatinine (SCr) and urea nitrogen (BUN) levels were detected by enzyme-linked immunosorbent assay. Pathological changes of kidney and colon tissues were observed by hematoxylin and eosin staining. Autophagosome changes in colonic epithelial cells was observed with electron microscopy. In vitro experiments, human colon cancer epithelial cells (T84) were cultured and divided into normal, urea model (74U), YS colon dialysis, autophagy activator rapamycin (Ra), autophagy inhibitor 3-methyladenine (3-MA), and SIRT1 activator resveratrol (Re) groups. RT-PCR and Western blot were used to detect the mRNA and protein expressions of zonula occludens-1 (ZO-1), Claudin-1, silent information regulator sirtuin 1 (SIRT1), LC3, and Beclin-1 both in vitro and in vivo. RESULTS: Colonic dialysis with YS decreased SCr and BUN levels in CRF rats (P<0.05), and alleviated the pathological changes of renal and colon tissues. Expressions of SIRT1, ZO-1, Claudin-1, Beclin-1, and LC3II/I were increased in the YS group compared with the CRF group in vivo (P<0.05). In in vitro study, compared with normal group, the expressions of SIRT1, ZO-1, and Claudin-1 were decreased, and expressions of Beclin-1, and LC3II/I were increased in the 74U group (P<0.05). Compared with the 74U group, expressions of SIRT1, ZO-1, and Claudin-1 were increased, whereas Beclin-1, and LC3II/I were decreased in the YS group (P<0.05). The treatment of 3-MA and rapamycin regulated autophagy and the expression of SIRT1. SIRT1 activator intervention up-regulated autophagy as well as the expressions of ZO-1 and Claudin-1 compared with the 74U group (P<0.05). CONCLUSION Colonic dialysis with YS could improve autophagy disorder and repair CRF intestinal mucosal barrier injury by regulating SIRT1 expression in intestinal epithelial cells.
Animals ; Sirtuin 1/metabolism* ; Drugs, Chinese Herbal/therapeutic use* ; Autophagy/drug effects* ; Male ; Intestinal Mucosa/drug effects* ; Rats, Sprague-Dawley ; Epithelial Cells/metabolism* ; Colon/drug effects* ; Humans ; Kidney Failure, Chronic/drug therapy* ; Signal Transduction/drug effects* ; Renal Dialysis ; Rats ; Kidney/drug effects*

OBJECTIVE: To evaluate the dynamic changes of glucocorticoid (GC) dose and the feasibility of GC discontinuation in rheumatoid arthritis (RA) patients under the background of Chinese medicine (CM). METHODS: This multicenter retrospective cohort study included 1,196 RA patients enrolled in the China Rheumatoid Arthritis Registry of Patients with Chinese Medicine (CERTAIN) from September 1, 2019 to December 4, 2023, who initiated GC therapy. Participants were divided into the Western medicine (WM) and integrative medicine (IM, combination of CM and WM) groups based on medication regimen. Follow-up was performed at least every 3 months to assess dynamic changes in GC dose. Changes in GC dose were analyzed by generalized estimator equation, the probability of GC discontinuation was assessed using Kaplan-Meier curve, and predictors of GC discontinuation were analyzed by Cox regression. Patients with <12 months of follow-up were excluded for the sensitivity analysis. RESULTS: Among 1,196 patients (85.4% female; median age 56.4 years), 880 (73.6%) received IM. Over a median 12-month follow-up, 34.3% (410 cases) discontinued GC, with significantly higher rates in the IM group (40.8% vs. 16.1% in WM; P<0.05). GC dose declined progressively, with IM patients demonstrating faster reductions (median 3.75 mg vs. 5.00 mg in WM at 12 months; P<0.05). Multivariate Cox analysis identified age <60 years [P<0.001, hazard ratios (HR)=2.142, 95% confidence interval (CI): 1.523-3.012], IM therapy (P=0.001, HR=2.175, 95% CI: 1.369-3.456), baseline GC dose ⩽7.5 mg (P=0.003, HR=1.637, 95% CI: 1.177-2.275), and absence of non-steroidal anti-inflammatory drugs use (P=0.001, HR=2.546, 95% CI: 1.432-4.527) as significant predictors of GC discontinuation. Sensitivity analysis (545 cases) confirmed these findings. CONCLUSIONS RA patients receiving CM face difficulties in following guideline-recommended GC discontinuation protocols. IM can promote GC discontinuation and is a promising strategy to reduce GC dependency in RA management. (Trial registration: ClinicalTrials.gov, No. NCT05219214).
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Arthritis, Rheumatoid/drug therapy* ; Glucocorticoids/therapeutic use* ; Medicine, Chinese Traditional ; Retrospective Studies