1.Effect of Modified Duhuo Jisheng Mixture Regulating PI3K/Akt/mTOR Signaling Pathway on Synoviocyte Pyroptosis in Rabbit Models of Knee Osteoarthritis
Zifeng YE ; Yiwei YUAN ; Liguo QIU ; Xuyi TAN ; Liang OU ; Gaoyan KUANG ; Min LU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(1):170-179
ObjectiveTo explore the potential mechanisms of action of the modified Duhuo Jisheng Mixture (JDJM) in treating synovial lesions in knee osteoarthritis (KOA). MethodsA total of 43 male New Zealand white rabbits were randomly allocated into a blank group (n=8) and a model group (n=35). The KOA model was induced by immobilizing the right hind limb with a high-molecular resin plaster bandage, with a modeling period of 6 weeks, resulting in successful modeling in 32 rabbits. These rabbits were then randomly allocated to the model group, celecoxib group, JDJM group and JDJM+740Y-P group, each consisting of 8 rabbits. The celecoxib group received celecoxib via gavage at a single dose of 0.009 3 g·kg-1, while the JDJM was administered a single dose of 6.8 mL·kg-1 (4.515 2 g·kg-1) of the herbal preparation via gavage. The phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) pathway activator + JDJM group received 4.515 2 g·kg-1 of the herbal preparation via gavage along with an auricular vein injection of 0.15 μmol·kg-1 740Y-P. For a period of 6 weeks, the remaining groups received an equal volume of physiological saline via gavage daily. After the medication period, the knee joint pain threshold and circumference were measured, and hematoxylin-eosin (HE) staining was performed to assess the pathological changes in the synovial tissues. Enzyme-linked immunosorbent assay (ELISA) measured the levels of interleukin-1β (IL-1β), interleukin-6 (IL-18) and tumor necrosis factor-α (TNF-α) in the joint fluid. Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) was used to assess the mRNA expression of PI3K, Akt, mTOR, NOD-like receptor protein 3 (NLRP3), cysteine-requiring aspartate protease-1 (Caspase-1) and gasdermin D (GSDMD) in the synovial tissues. Immunohistochemical (IHC) assay was performed to assess the protein expression of NLRP3, Caspase-1 and GSDMD. Western blot was carried out to analyze the protein expression of p-PI3K/PI3K, p-Akt/Akt, p-mTOR/mTOR, NLRP3, Caspase-1 and GSDMD. ResultsCompared to the blank group, the model group showed a significant increase in knee joint circumference and decrease in pain threshold, the synovial tissue pathology score was higher (P<0.05), and the levels of IL-1β, IL-18, and TNF-α in the joint fluid significantly increased (P<0.01). PI3K, Akt, mTOR phosphorylation as well as mRNA and protein expression increased (P<0.01), while the mRNA and protein expression levels of NLRP3, Caspase-1 and GSDMD also significantly increased (P<0.01). Compared to the model group, the celecoxib and JDJM groups exhibited a significant reduction in knee joint circumference and increase in pain threshold, the synovial tissue pathology score was lower (P<0.05), and the levels of IL-1β, IL-18, and TNF-α in the joint fluid decreased (P<0.01). The mRNA and protein expression of p-PI3K, p-Akt, p-mTOR, NLRP3, Caspase-1 and GSDMD were reduced (P<0.01). Compared to the JDJM group, the JDJM+740Y-P group showed a decrease in the improvement of synovial lesions, an increase in knee joint circumference, and a decrease in pain threshold. The synovial tissue pathology score was lower (P<0.05), and the levels of IL-1β, IL-18, and TNF-α in the joint fluid were higher (P<0.01). The mRNA and protein expression of p-PI3K/PI3K, p-Akt/Akt, p-mTOR/mTOR, NLRP3, Caspase-1 and GSDMD increased (P<0.01). ConclusionJDJM is effective in treating KOA. Its mechanism may involve modulating the PI3K/Akt/mTOR pathway in synovial tissues, inhibiting pyroptosis, reducing inflammatory factor release, and protecting bony structures.
2.Preclinical mouse models for studying cholangiocarcinoma
Shanru Yang ; Chaodi Bao ; Yuan Li ; Yangxiang Ou ; Yifan Jiang ; Wenjie Xu ; Dongfang Zheng ; Na Li ; Mengjie Yang ; Fuyan Wang ; Xin Hou
Liver Research 2026;10(1):22-34
Cholangiocarcinoma (CCA) is a malignancy characterized by tumor cells originating in the liver or bile ducts, exhibiting features of cholangiocyte differentiation. It poses a significant clinical challenge due to the limited diagnostic and therapeutic options available. Robust animal models are essential for advancing our understanding of CCA pathogenesis and developing effective treatments. This review provides a comprehensive overview of CCA mouse models, highlighting various approaches, including chemical induction, genetically engineered models, and tumor xenografts. Each model is discussed in terms of its establishment techniques, pathological characteristics, and research significance, with a focus on intrahepatic CCA. Chemical induction models, such as diethylnitrosamine- and azoxymethane-induced models, offer insights into tumorigenesis processes, whereas genetically modified models involving alterations in key genes such as Kirsten rat sarcoma viral oncogene homolog, tumor protein 53, and isocitrate dehydrogenase serve as important tools for studying the molecular mechanisms underlying CCA. Xenograft models, including patient-derived xenografts, bridge the gap between experimental research and clinical applications, allowing for precise therapeutic evaluations. By comparing these models, this review underscores their respective advantages and limitations, paving the way for future studies aiming to optimize and innovate CCA modeling strategies.
3.Integrating O-RADS,Contrast-enhanced Ultrasound and ROMA z-score for Three-category Prediction of Ovarian Epithelial Tumors
Kun YUAN ; Xiaomin ZHU ; Huanyu ZHANG ; Yujun HUANG ; Qingying LI ; Yan OU ; Yunxiao ZHU
Journal of Sun Yat-sen University(Medical Sciences) 2026;47(2):336-345
ObjectiveTo develop and evaluate an O-RADSbased multiparametric model integratingcontrast-enhanced US (CEUS) and the z-score standardized risk of ovarian malignancy algorithm (ROMA z-score) to improve the diagnostic accuracy for differentiating benign, borderline, and malignant ovarian epithelial tumors (OETs). MethodsThis retrospective study included 129 patients with pathologically confirmed OETs between May 2018 and December 2024. Clinical variables (age, menopausal status, BMI, HE4, CA125) and sonographic features (conventional US and CEUS) were collected. Tumors were classified as benign, borderline, or malignant according to pathological findings. A random forest algorithm was used to contruct the predictive model. Receiver operating characteristic (ROC) curves were generated tocompare the diagnostic performance of O-RADS, O-RADS+CEUS, O-RADS+ROMA z-score, and O-RADS+ CEUS+ROMA z-score. ResultsAmong the 129 patients, 63 had benign tumors, 25 had borderline tumors, and 41 had malignant tumors. Compared with O-RADS alone, the combined O-RADS+CEUS+ROMA z-score model demonstrated superior diagnostic performance, with an AUC of 0.87 (95% CI: 0.79-0.95) vs. 0.64 (95% CI: 0.51-0.76), P<0.001, for differentiating benign from borderline tumors, and 0.90 (95% CI: 0.83-0.97) vs. 0.64 (95% CI: 0.50-0.78), P<0.001, for differentiating borderline from malignant tumors. The random forest analysis identified HE4, CA125 and CEUS features as the most important predictors,contributing 11.02, 8.82, 18.1 points, respectively, to the total importance score of 51.94. In the test cohort, the model achieved an overall diagnostic accuracy of 72.97%, with an AUC of 0.89(95%CI:0.77-1.00), sensitivity of 67.06%, and specificity of 85.01%. ConclusionsO-RADS+CEUS+ROMA z-score multiparametric model demonstrated the highest diagnostic performance for in differentiating benign from borderline and borderline from malignant OETs. HE4, CA125 and CEUS features were identified as key predictive risk factors, supporting the role of this model in improving preoperative risk stratification of OETs.
4.Flavonoids from Corn Silk (Zea mays L.) and its pharmacological effects
Licheng ZHOU ; Yiming OU ; Yuan WANG
Journal of Pharmaceutical Practice and Service 2025;43(2):51-58
Corn silk, a Traditional Chinese Medicine, has the effect of calming liver, cholagogue, detumescence and diuresis. Corn silk is also widely used as tea and functional food. Natural flavonoids have multiple biological activities, which are also the main bioactive components of corn silk. In the past decade, many new advances have been made in the chemistry, analysis, pharmacology, pharmacokinetics, and safety evaluation of corn silk flavonoids. The chemical composition research of flavonoids has enriched the variety of flavonoids in corn silk. Pharmacological studies have confirmed and expanded the efficacy of corn silk flavonoids. And safety evaluation has provided a theoretical basis for the safe application of corn silk flavonoids. Through literature search, the extraction, separation, compositional analysis, content determination, pharmacological effect, pharmacokinetics, and safety research progress of corn silk flavonoids in the past ten years were reviewed in this paper.
5.Guben Fangxiao decoction Regulates Expression of CGRP /ILC2 and GABA in Human Bronchial Epithelial Cells Stimulated with IL-4 Combined with IL-13
Weiying OU ; Xuejing YUAN ; Jianjian JI
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(2):93-100
ObjectiveTo observe the effects of Guben Fangxiao decoction-containing serum on the expression of transcription factors and cytokines associated with calcitonin gene-related peptide (CGRP), γ-aminobutyric acid (GABA), and type Ⅱ innate lymphoid cells (ILC2) in human bronchial epithelial cells (BEAS-2B) stimulated with interleukin-4 (IL-4) combined with interleukin-13 (IL-13), and explore the possible mechanism of Guben Fangxiao decoction-containing serum in alleviating type Ⅱ inflammation of bronchial epithelial cells. MethodsBEAS-2B cells stimulated with IL-4 combined with IL-13 were treated with the sera containing high (20%), medium (15%), and low (10%) doses of Guben Fangxiao decoction and the montelukast-containing serum (10%). Real-time PCR was used to measure the mRNA levels of CGRP, GABA, mucin 5AC (MUC5AC), thymic stromal lymphopoietin (TSLP), interleukin (IL)-25, IL-33, IL-5, GATA-binding protein 3 (GATA3), and B cell lymphoma/leukemia 11B (Bcl-11B) in each group. Western blot was employed to determine the relative protein levels of CGRP and MUC5AC. The immunofluorescence assay was employed to observe the relative expression of CGRP and GABA in the cells. Enzyme-linked immunosorbent assay was used to quantify the protein levels of IL-33, MUC5AC, and IL-5 in the culture and cell supernatants. Periodic acid-Schiff staining was performed to assess mucin secretion. ResultsCompared with the control group, the model group showed up-regulated mRNA levels of CGRP, GABA, MUC5AC, TSLP, IL-25, and IL-33 (P<0.05, P<0.01). Compared with the normal group, the Guben Fangxiao decoction-containing serum down-regulated the mRNA levels of CGRP, GABA, MUC5AC, IL-5, GATA3, and Bcl-11B (P<0.05, P<0.01) in a dose-dependent manner. Compared with the normal group, the model group showed up-regulated protein levels of CGRP, GABA, MUC5AC, IL-33, and IL-5 (P<0.05, P<0.01), which were down-regulated by the Guben Fangxiao decoction-containing serum (P<0.05, P<0.01). Compared with the normal group, the model group showed enhanced average fluorescence intensity of CGRP and GABA (P<0.01), which was weakened by the Guben Fangxiao decoction-containing serum (P<0.01). Compared with the normal group, the model group showed increased secretion of mucin, which was reduced by the Guben Fangxiao decoction-containing serum. ConclusionGuben Fangxiao decoction can treat bronchial asthma by alleviating type Ⅱ immune airway inflammation and reducing airway mucus secretion, which is achieved by regulating the expression of CGRP, GABA, MUC5AC, and ILC2-related transcription factors.
6.Comprehensive application of fingerprint studies, content determination, and chemometrics to identify geo-markers of Chuanxiong Rhizoma.
Meng-Yuan WU ; Cheng PENG ; Chun-Wang MENG ; Juan-Ru LIU ; Qin-Mei ZHOU ; Ou DAI ; Liang XIONG
China Journal of Chinese Materia Medica 2025;50(1):152-171
This study established a high performance liquid chromatography(HPLC) fingerprint of Chuanxiong Rhizoma from different producing areas and screened its potential differential components for producing areas by chemometrics. Furthermore, the content of the above differential components in Chuanxiong Rhizoma from different producing areas was measured and compared. Then, the geoherbalism markers(geo-markers) that can be used to distinguish Dao-di and non-Dao-di Chuanxiong Rhizoma were excavated by chemometrics. In fingerprint studies, a total of 27 common peaks were determined, and the fingerprint similarity for 37 batches of Chuanxiong Rhizoma samples from different producing areas was above 0.968. The orthogonal partial least squares-discriminant analysis(OPLS-DA) was capable of distinguishing Chuanxiong Rhizoma from Sichuan and from three other provinces, as well as Dao-di Chuanxiong Rhizoma(from Dujiangyan) and non-Dao-di Chuanxiong Rhizoma(from other producing areas) in Sichuan province. Meanwhile, 14 potential differential components in Chuanxiong Rhizoma from different provinces and 16 potential differential components in Chuanxiong Rhizoma from different producing areas in Sichuan were screened by the variable importance in projection(VIP) analysis under OPLS-DA. The reference standards were used to identify 10 potential differential components in the common peaks, and subsequent content determination verified that the content of the above 10 potential differential components was different among different producing areas. Then, the OPLS-DA and VIP analysis were performed with the content of the 10 potential differential components as variables. The results showed that Z-ligustilide, chlorogenic acid, and the ratio of butylidenephthalide/senkyunolide A were the geo-markers that can distinguish Chuanxiong Rhizoma from Sichuan and Chuanxiong Rhizoma from Shaanxi, Hebei, and Jiangxi, while Z-ligustilide, n-butylphthalide, and the ratios of Z-ligustilide/senkyunolide A and butylidenephthalide/senkyunolide A were the geo-markers that can distinguish Dao-di Chuanxiong Rhizoma(from Dujiangyan) and non-Dao-di Chuanxiong Rhizoma(from other producing areas) in Sichuan province. This study elucidated the differences in material basis of Dao-di and non-Dao-di Chuanxiong Rhizoma based on fingerprinting and content determination combined with chemometrics, which provides a reference for the study of material basis of Dao-di traditional Chinese medicine.
Drugs, Chinese Herbal/chemistry*
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Rhizome/chemistry*
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Chromatography, High Pressure Liquid/methods*
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Chemometrics/methods*
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Quality Control
8.Role of TLR5 in pathogenesis of obesity-related hypertension:Current evidence and future challenges
Ou WU ; Xiaoxiao MI ; Hu ZHANG ; Chengda YUAN ; Jin GAO
Chinese Journal of Immunology 2025;41(2):484-489
Toll-like receptor 5(TLR5)is a pattern recognition receptor,the main extracellular receptor for recognizing flagel-lin,and a bridge between innate and adaptive immunity.It can activate innate immunity and induce the release of a series of down-stream cytokines,as well as play an important role in protecting the host from flagellated pathogens and establishing immune tolerance.These functions are related to the pathogenesis of obesity hypertension in various aspects.This article aims to review the relationship between TLR5 and obese hypertension,as well as the new progress on the interaction between TLR5 and flagellin structure and func-tion,and discuss the future research directions and challenges.
9.The impact of admission modes on the reperfusion time and short-term prognosis of patients with acute ST-segment elevation myocardial infarction
Ji-yi LIN ; Wei-mei OU ; Wei-wei HUANG ; Yan WANG ; Shao-qing LIN ; Yuan CHEN ; Bin WANG
Chinese Journal of Interventional Cardiology 2025;33(8):447-453
Objective To explore the impact of admission modes on the reperfusion time and short-term prognosis of patients with acute ST-segment elevation myocardial infarction(STEMI).Methods 497 patients who visited the Chest Pain Center of Xiamen Cardiovascular Hospital of Xiamen University from January 2023 to November 2024 and were diagnosed with STEMI were included.All patients received direct percutaneous coronary intervention.According to admission modes,the patients were divided into the self-referral group(122 cases),emergency medical service group(EMS)(51 cases)and transfer PCI group(324 cases).The basic characteristics,reperfusion time,complications between group were compared.Results The age of the patients in this study was(58.64±13.62)years old,and there were 423 male cases(85.11%).Compared with the self-referral group and the EMS group,the time of door-wire in transfer PCI group was shorter[35(29,45)min vs.43(35,53)min vs.43(33,48)min,P<0.001],but the time of first medical contact-wire was longer[123(80,192)min vs.43(35,52)min vs.57(51,76)min,P<0.001].Compared with the self-referral group and the transfer PCI group,the time of symptom-to-first medical contact and the time of symptom-to-wire in EMS group were both shorter,which were[55(32,136)min vs.185(116,360)min vs.120(60,236)min,P<0.001]and[136(101,188)min vs.228(169,413)min vs.282(190,400)min,P<0.001].The incidence of infections in the transfer PCI group was lower than that in the self-referral group(12.65%vs.22.95%,P<0.05).Conclusions To comprehensively enhance the treatment effect,it is necessary to prioritize the promotion and continuous optimization of the response process of EMS,simultaneously strengthen the standardized collaboration of referral,and enhance the identification ability of STEMI through public education to reduce the delay of self-referral patients..
10.Associations of parenting style and depressive symptoms with nightmare disorder in adolescents
ZHU Qisha, ZHAO Yuan, CHEN Qiuxia, HU Jun, XU Ou
Chinese Journal of School Health 2025;46(4):539-543
Objective:
To explore the relationship between parenting styles and depressive symptoms in adolescents with nightmare disorder, so as to provide a scientific basis for formulating effective family intervention measures and psychological counseling.
Methods:
From January 2023 to August 2024, 90 adolescents diagnosed with nightmare disorder and admitted to Hangzhou Seventh Peoples Hospital, along with 176 healthy controls from the urban areas of Hangzhou, were recruited as participants in the study. All participants were assessed using the Nightmare Experience Questionnaire (NEQ), Family Relationship Questionnaire (FRQ), and Plutchik-van Praag Selfreport Depression Scale (PVP). The ttest and Chisquare test were conducted to compare two groups. Pearson correlation and stepwise multiple linear regression were employed to explore the correlations between PVP and NEQ or FRQ. The Process model was used to testing the mediating effects among NEQ/FRQ/PVP.
Results:
The nightmare disorder group had higher scores in nightmare frequency, the four factors of NEQ (physical effect, negative emotion, meaning interpretation, horrible stimulation), and PVP than the healthy control group (24.86±18.89, 10.12±3.67, 19.01±3.51, 17.02±3.31, 15.14±3.26, 14.02±4.38; 2.34±1.04, 6.49±2.18, 17.63±4.76, 13.91±4.24, 12.40±4.49, 9.39±3.28)(t=15.79, 10.11, 2.43, 6.09, 5.14, 27.46, P<0.05). The nightmare disorder group reported significantly lower scores in FRQ general attachment and maternal encouragement than the healthy control group (7.22±2.81, 16.39±3.28) (t=-5.53, -4.95). In contrast, they exhibited significantly higher scores in maternal abuse, maternal dominance, paternal freedom release, and paternal dominance than the healthy control group (8.23±1.80, 13.11±3.73, 18.36±3.37, 12.04±3.29; 6.07±1.85, 8.48±3.80, 15.15±2.51, 9.47±3.03) (t=6.70, 8.96, 5.90, 7.04, P<0.01). The results of Pearson correlation analysis showed that, in the nightmare disorder group, the PVP score was positively correlated with negative emotion, nightmare frequency, maternal abuse, and maternal dominance score (r=0.14, 0.63, 0.26, 0.51, P<0.05). The results of multiple linear regression analysis showed that when using FRQ score to predict NEQ score, the adjusted R2 in the nightmare disorder group was 0.01-0.59. Mother abuse could prediced physical effect (β=0.33); maternal dominance significantly predicted negative emotion, horrible stimulation, and nightmare frequency (β=0.29, 0.30, 0.79); paternal freedom release could predict negative emotion (β=0.26), paternal dominance predicted both negative emotion and nightmare frequency (β=0.22, 0.45) (P<0.05). Mediation analysis further revealed that, in the nightmare disorder group, PVP scores served as a mediating variable between FRQ and NEQ.
Conclusion
Abusive, controlling, and neglectful family upbringing styles as well as depression maybe are key factors that may contribute to the development of nightmare disorder among adolescents.


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