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*

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

OBJECTIVE: To investigate the association between ABO blood types and gestational diabetes mellitus (GDM) risk. METHODS: A prospective birth cohort study was conducted. ABO blood types were determined using the slide method. GDM diagnosis was based on a 75-g, 2-h oral glucose tolerance test (OGTT) according to the criteria of the International Association of Diabetes and Pregnancy Study Groups. Logistic regression was applied to calculate the odds ratios ( ORs) and 95% confidence intervals ( CIs) between ABO blood types and GDM risk. RESULTS: A total of 30,740 pregnant women with a mean age of 31.81 years were enrolled in this study. The ABO blood types distribution was: type O (30.99%), type A (26.58%), type B (32.20%), and type AB (10.23%). GDM was identified in 14.44% of participants. Using blood type O as a reference, GDM risk was not significantly higher for types A ( OR = 1.05) or B ( OR = 1.04). However, women with type AB had a 19% increased risk of GDM ( OR = 1.19, 95% CI = 1.05-1.34; P < 0.05), even after adjusting for various factors. This increased risk for type AB was consistent across subgroup and sensitivity analyses. CONCLUSION The ABO blood types may influence GDM risk, with type AB associated with a higher risk. Incorporating it-either as a single risk factor or in combination with other known factors-could help identify individuals at risk for GDM before or during early pregnancy.
Humans ; Female ; Pregnancy ; Diabetes, Gestational/etiology* ; ABO Blood-Group System ; Adult ; Prospective Studies ; Risk Factors ; Young Adult

Objective To analyze the multi-target mechanism of Paeoniflorin in the intervention of oral submucosal fibrosis(OSF)systematically,based on molecular dynamics simulation and network pharmacology.Methods Identify potential targets of Paeoniflorin were predicted by using database.OSF-related disease targets and identified drug-disease intersecting targets were screened.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis were conducted to validate the molecular binding capabilities between Paeoniflorin and core targets.Finally,molecular dynamics simulations were performed to verify binding stability.Results A total of 20 overlapping targets were identified,including key genes such as transforming growth factor(TGF)-β1,interleukin(IL)-6,and tumor necrosis factor(TNF)-α.TGF-β1,IL-6,and TNF formed the core hub.The enrichment analysis revealed that the target molecules were significantly enriched in the TGF-β1,phosphatidylinositol 3-kinease-actin(PI3K-Akt),and nuclear factor κB(NF-κB)signaling pathways.Molecular docking confirmed high affinity binding of Paeoniflorin to targets including TGF-β1,while molecular dynamics simulations verified stable interactions between Paeoniflorin and both TGF-β1 and B-cell lymphoma-2 targets.Conclusion This study revealed that Paeoniflorin inhibits the inflammatory-fibrotic cascade of OSF through synergistic regulation of TGF-β1/Smad,PI3K-Akt and NF-κB pathways.

Objective To explore the relationship between dynamic contrast-enhanced magnetic resonance imaging(DCE-MRI)and clinical pathological features of invasive breast cancer and lymphovascular invasion(LVI).Methods Imaging and clinical pathological data were retrospectively collected from 508 patients with invasive breast cancer who underwent breast DCE-MRI at the First Medical Center of Chinese PLA General Hospital from January 2019 to August 2021.Patients were divided into the LVI-positive(LVI+)group(n=79)and LVI-negative(LVI-)group(n=429)based on postoperative pathological results.Univariate and multivariate logistic regression analyses were used to identify risk factors for LVI.Results Compared with LVI-group,LVI+group had a higher proportion of patients aged<45 years(44.3%vs.27.0%,P=0.002),non-mass-like enhancement(NME)(31.7%vs.17.7%,P=0.004),Ki-67 expression rate(40.0%vs.30.0%,P<0.001),high Ki-67 expression(94.9%vs.78.1%,P=0.001),Luminal B subtype(76.0%vs.60.1%,P=0.008),and positive axillary lymph nodes rate(72.2%vs.31.5%,P<0.001),while the proportion of Luminal A subtype was lower(2.5%vs.21.5%,P<0.001).Univariate and multivariate logistic regression analyses showed that age≥45 years(OR=0.468,95%CI 0.280-0.783,P=0.004)was an independent protective factor for LVI,while NME(OR=1.987,95%CI 1.126-3.444,P=0.016)was an independent risk factor.Compared with Luminal A subtype,patients with Luminal B subtype(OR=10.482,95%CI 3.164-64.923,P=0.001),HER-2 overexpression subtype(OR=11.571,95%CI 2.755-79.341,P=0.003)and triple-negative subtypes(OR=8.433,95%CI 1.985-57.908,P=0.009)had a higher risk of LVI.Conclusions Age≥45 years is an independent protective factor for LVI,while NME is an independent risk factor.Among molecular subtypes,patients with Luminal B,HER-2 overexpression and triple-negative subtypes have a higher risk of LVI compared with the Luminal A subtype.

Aim To evaluate the role of the glucose transporter protein 1(GLUT1)-dependent glycolytic in the attenuation of oxygen-glucose deprivation-reoxygen-ation(OGD/R)injury in HK-2 cells by dexmedetomi-dine(Dex).Methods C57/BL6 mice were random-ly divided into three groups(n=6),namely,sham operation group(Sham group),renal ischemia reper-fusion group(I/R group)and Dex group(I/R+Dex group).Serum creatinine(Cr)and urea nitrogen(BUN)were measured,while the levels of key glyco-lytic enzymes HK2,PFKFB3 and GLUT1 were meas-ured.HK-2 cells were cultured and randomised into seven groups(n=6),which was treated with OGD/R,overexpression or interference with GLUT1,Dex and glycolysis inhibitor 2-DG.CCK-8 and LDH activi-ty were used to detect cellular damage.Glycolysis lev-els were detected by lactate and ECAR.The inflamma-tory level was reflected by qRT-PCR for IL-6 and TNF-α.qRT-PCR and Western blot were performed to de-tect the levels of GLUT1,HK2,and PFKFB3.Results Dex significantly ameliorated kidney injury and HK-2 cell injury(P＜0.05).Dex inhibited the OGD/R-induced rise in lactate and extracellular acidification rate(ECAR),as evidenced by suppression of the ex-pression of GLUT1,HK2 and PFKFB3(P＜0.05).In vitro experiments showed that GLUT1 knockdown sig-nificantly improved OGD/R-induced cellular damage.Lactate,ECAR,glycolysis-related mRNAs and pro-teins were inhibited by GLUT1 knockdown(P＜0.05).Significantly,there were no significant differ-ences in above indexes after Dex treatment based on GLUT1 knockdown.Overexpression of GLUT1 abroga-ted the protective effects of Dex,while reversing the inhibitory effects of Dex on the expression of GLUT1,HK2,and PFKFB3(P＜0.05).Conclusions Dexmedetomidine attenuates OGD/R induced injury in HK-2 cells by inhibiting GLUT1-dependent glycolysis.

Objective:To establish an arsenic free fully automatic online digestion iodine analyzer detection method for urinary iodine (hereinafter referred to as the method).Methods:Based on the principle of iodine catalyzed antimony cerium redox reaction, a fully automatic online digestion iodine analyzer was used to determine the iodine content in urine. The effectiveness of the method in terms of detection limit, precision, accuracy (determination of urinary iodine primary standard reference materials GBW09108z and GBW09110f and spiked recovery experiment), and interference experiments was validated. The method was compared with the arsenic cerium catalytic spectrophotometry method recommended by the National Reference Laboratory for Iodine Deficiency Disorders.Results:The linear range of the method was 0 - 300 μg/L, with a correlation coefficient │ r│> 0.999 5. The qualitative and quantitative detection limits were 7.41 and 18.01 μg/L, respectively. The relative standard deviation ( RSD) of urine samples with different iodine concentrations ranged from 1.0% to 1.7%. The results of the determination of iodine concentrations in urine using standard substances GBW09108z and GBW09110f were within the given standard range, with RSD < 2.5%. The range of spiked recovery rates for urine samples with different iodine concentrations was 101.3% to 104.8%, with an overall average spiked recovery rate of 103.0%. The average concentration of the baseline iodine standard solution was determined to be 116.21 μg/L, and the relative error of the concentration determination with the addition of interfering substances was less than 5.0%. The comparison results showed that there was no statistically significant difference in the measurement results between the two methods ( t = - 0.06, P = 0.952). Conclusions:The method adopts automated detection, which is simple to operate, labor-saving, and does not require the use of arsenic trioxide. It has high precision and accuracy, and is suitable for detection of large quantities of samples.

Objective By simulating the etiology of abnormal uterine bleeding-ovulatory dysfunction(AUB-O)and establishing a rat model of abnormal uterine bleeding(AUB),this study aims to provide an experimental platform for investigating pathological mechanisms and developing therapeutic drugs for AUB.Methods After acclimation,24 adult(10-week-old)female SD rats were randomly divided into a normal control group(6 rats)and a model group(18 rats).The normal control group was housed in a barrier environment,while the model group underwent bilateral ovariectomy via dorsal approach in the same environment and rested for one week before starting to receive modeling drugs.In the model group,from Days 1 to 3 of modeling,each rat received a daily subcutaneous injection of 0.5 mg estradiol into the dorsal region.From Days 4 to 7,a daily subcutaneous injection of 5.0 mg progesterone was administered.On Day 6,rats received bilateral injections of 0.5 mL soybean oil per uterine cavity(total 1.0 mL)via the same dorsal surgical incision.On Day 8,mifepristone(10 mg/kg)was administered via oral gavage.The estrous cycle stage and its dynamic changes were continuously monitored during modeling.Uterine bleeding was recorded during the 48-hour observation period post-modeling.Serum and uterine tissue samples were collected from the model group at 0,12,24,36,and 48 h after mifepristone administration,while the normal control group was sampled at 36 h.The samples were subjected to HE staining,serum sex hormone ELISA,immunohistochemistry,TUNEL apoptosis staining,Western blotting,transcriptome sequencing,and bioinformatics analysis for comprehensive evaluation of the AUB rat model.Results The AUB rats exhibited uterine bleeding,endometrial detachment and injury,incomplete uterine restoration,inflammatory cell infiltration in the endometrium,enhanced tissue apoptosis,and structural damage of the stroma,glands,and vasculature.Compared with the normal control group,the levels of serum follicle-stimulating hormone(FSH),estradiol,and luteinizing hormone(LH)were significantly increased in the AUB rats(P＜0.05).The vascular density of the endometrium was significantly reduced(P＜0.05).The expression of vascular endothelial growth factor(VEGF)was qualitatively observed to be markedly enhanced at the site of endometrial detachment but significantly decreased around the stromal blood vessels(P＜0.01).Matrix metalloproteinase-9(MMP-9)expression was qualitatively observed to be strongly upregulated at the site of endometrial injury but significantly reduced in the non-detached stroma and glands(P＜0.01).Endometrial stromal cell apoptosis was significantly enhanced(P＜0.01).The expression levels of fibroblast growth factor 2(FGF2)and endothelin-1(ET-1)in uterine tissues were significantly decreased(P＜0.05).After comparing the transcriptome sequencing results of uterine tissues between AUB and normal rats,a total of 4 723 differentially expressed genes were identified,including 2 191 up-regulated genes and 2 532 down-regulated genes.KEGG enrichment analysis revealed that these differentially expressed genes were significantly enriched in pathways related to inflammation,immune apoptosis,cell signal transduction,proliferation and differentiation,and muscle contraction,among others.Conclusion An AUB rat model can be successfully established using a sequential administration protocol of estrogen,progesterone,and mifepristone to simulate the etiology of AUB-O.In this model,endometrial injury is associated with inflammation and apoptosis,with pathological manifestations influenced by abnormal vasoconstriction and impaired endometrial regeneration.This rat model closely recapitulates pathological characteristics of non-structural AUB observed in clinical practice,making it a validated experimental platform for exploring the pathological mechanisms and therapeutic interventions of non-structural AUB.

Objective By simulating the etiology of abnormal uterine bleeding-ovulatory dysfunction(AUB-O)and establishing a rat model of abnormal uterine bleeding(AUB),this study aims to provide an experimental platform for investigating pathological mechanisms and developing therapeutic drugs for AUB.Methods After acclimation,24 adult(10-week-old)female SD rats were randomly divided into a normal control group(6 rats)and a model group(18 rats).The normal control group was housed in a barrier environment,while the model group underwent bilateral ovariectomy via dorsal approach in the same environment and rested for one week before starting to receive modeling drugs.In the model group,from Days 1 to 3 of modeling,each rat received a daily subcutaneous injection of 0.5 mg estradiol into the dorsal region.From Days 4 to 7,a daily subcutaneous injection of 5.0 mg progesterone was administered.On Day 6,rats received bilateral injections of 0.5 mL soybean oil per uterine cavity(total 1.0 mL)via the same dorsal surgical incision.On Day 8,mifepristone(10 mg/kg)was administered via oral gavage.The estrous cycle stage and its dynamic changes were continuously monitored during modeling.Uterine bleeding was recorded during the 48-hour observation period post-modeling.Serum and uterine tissue samples were collected from the model group at 0,12,24,36,and 48 h after mifepristone administration,while the normal control group was sampled at 36 h.The samples were subjected to HE staining,serum sex hormone ELISA,immunohistochemistry,TUNEL apoptosis staining,Western blotting,transcriptome sequencing,and bioinformatics analysis for comprehensive evaluation of the AUB rat model.Results The AUB rats exhibited uterine bleeding,endometrial detachment and injury,incomplete uterine restoration,inflammatory cell infiltration in the endometrium,enhanced tissue apoptosis,and structural damage of the stroma,glands,and vasculature.Compared with the normal control group,the levels of serum follicle-stimulating hormone(FSH),estradiol,and luteinizing hormone(LH)were significantly increased in the AUB rats(P＜0.05).The vascular density of the endometrium was significantly reduced(P＜0.05).The expression of vascular endothelial growth factor(VEGF)was qualitatively observed to be markedly enhanced at the site of endometrial detachment but significantly decreased around the stromal blood vessels(P＜0.01).Matrix metalloproteinase-9(MMP-9)expression was qualitatively observed to be strongly upregulated at the site of endometrial injury but significantly reduced in the non-detached stroma and glands(P＜0.01).Endometrial stromal cell apoptosis was significantly enhanced(P＜0.01).The expression levels of fibroblast growth factor 2(FGF2)and endothelin-1(ET-1)in uterine tissues were significantly decreased(P＜0.05).After comparing the transcriptome sequencing results of uterine tissues between AUB and normal rats,a total of 4 723 differentially expressed genes were identified,including 2 191 up-regulated genes and 2 532 down-regulated genes.KEGG enrichment analysis revealed that these differentially expressed genes were significantly enriched in pathways related to inflammation,immune apoptosis,cell signal transduction,proliferation and differentiation,and muscle contraction,among others.Conclusion An AUB rat model can be successfully established using a sequential administration protocol of estrogen,progesterone,and mifepristone to simulate the etiology of AUB-O.In this model,endometrial injury is associated with inflammation and apoptosis,with pathological manifestations influenced by abnormal vasoconstriction and impaired endometrial regeneration.This rat model closely recapitulates pathological characteristics of non-structural AUB observed in clinical practice,making it a validated experimental platform for exploring the pathological mechanisms and therapeutic interventions of non-structural AUB.

Objective To analyze the multi-target mechanism of Paeoniflorin in the intervention of oral submucosal fibrosis(OSF)systematically,based on molecular dynamics simulation and network pharmacology.Methods Identify potential targets of Paeoniflorin were predicted by using database.OSF-related disease targets and identified drug-disease intersecting targets were screened.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis were conducted to validate the molecular binding capabilities between Paeoniflorin and core targets.Finally,molecular dynamics simulations were performed to verify binding stability.Results A total of 20 overlapping targets were identified,including key genes such as transforming growth factor(TGF)-β1,interleukin(IL)-6,and tumor necrosis factor(TNF)-α.TGF-β1,IL-6,and TNF formed the core hub.The enrichment analysis revealed that the target molecules were significantly enriched in the TGF-β1,phosphatidylinositol 3-kinease-actin(PI3K-Akt),and nuclear factor κB(NF-κB)signaling pathways.Molecular docking confirmed high affinity binding of Paeoniflorin to targets including TGF-β1,while molecular dynamics simulations verified stable interactions between Paeoniflorin and both TGF-β1 and B-cell lymphoma-2 targets.Conclusion This study revealed that Paeoniflorin inhibits the inflammatory-fibrotic cascade of OSF through synergistic regulation of TGF-β1/Smad,PI3K-Akt and NF-κB pathways.