1.Mechanism of Icariin in Regulating TGF-β1/Smad Pathway to Induce Autophagy in Human Bone Microvascular Endothelial Cells
Yaqi ZHANG ; Yankun JIANG ; Guoyuan SUN ; Bo LI ; Ran DING ; Cheng HUANG ; Weiguo WANG ; Qidong ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(5):123-130
ObjectiveTo investigate the regulatory effect of icariin (ICA) on transforming growth factor-β1 (TGF-β1)/Smad pathway in bone microvascular endothelial cells (BMECs) and the effect on autophagy in BMECs. MethodsBMECs were isolated and cultured, and the cell types were identified by immunofluorescence. Cells were divided into the control group, model group (0.1 g·L-1 methyl prednisolone), ICA group (0.1 g·L-1 methyl prednisolone +1×10-5 mol·L-1 ICA), and TGF-β inhibitor group (0.1 g·L-1 methyl prednisolone +1×10-5 mol·L-1 ICA +1×10-5 mol·L-1 LY2157299). Transmission electron microscopy was used to observe the ultrastructure and autophagosome number of BMECs. Autophagy double-standard adenovirus was used to monitor the confocal autophagy flow generation of each cell. Real-time quantitative polymerase chain reaction (Real-time PCR) and Western blot were used to detect the gene and protein expression of autophagy in the TGF-β1/ Smad pathway. ResultsAfter cell separation culture, platelet endothelial cell adhesion molecule (CD31) and von willebrand factor (vWF) immunofluorescence identified BMECs. Transmission electron microscopy showed that the cell membrane was damaged, and the nucleus was pyknotic and broken in the model group. Compared with the model group, the ICA group had complete cell membranes, clear structures, with autophagy-lysosome sparsely distributed. The confocal photo showed that BMECs had autophagosomes and autophagy-lysosomes, and the autophagy expression of the ICA group was similar to that of the blank group. Compared with the blank group, in the model group and the LY2157299 group, autophagosomes and autophagy-lysosomes were barely seen in the autophagy flow. Compared with the blank group, the mRNA and protein expressions of autophagy effector protein 1 (Beclin1) and microtubule-associated protein 1 light chain 3B (LC3B) in the model group were significantly decreased (P<0.01), and those of ubiquitin-binding protein (p62) were significantly increased (P<0.01). The mRNA expression of TGF-β1, Smad homolog 2 (Smad2), and Smad homolog 3 (Smad3) decreased (P<0.05, P<0.01). The protein expressions of TGF-β1, p-Smad2, and p-Smad3 were significantly decreased (P<0.01). Compared with those of the model group, the mRNA and protein expression of Beclin1 and LC3B in BMECs of the ICA group increased (P<0.01), and those of p62 significantly reduced (P<0.01). The mRNA expression of TGF-β1, Smad2, and Smad3 increased significantly (P<0.01). The protein expression of TGF-β1, p-Smad2, and p-Smad3 increased significantly (P<0.01). Compared with those in the model group, the mRNA and protein expressions of Beclin1, LC3B, and p62 in the inhibitor group were not statistically significant. The expression of key genes and proteins of the TGF-β1 pathway in the inhibitor group was not statistically significant. ConclusionICA can promote glucocorticoid-induced autophagy expression of BMECs, and its mechanism may be related to activating the TGF-β1/Smad signaling pathway.
2.Effect of Icariin on Steroid-induced Ferroptosis in Rat Bone Microvascular Endothelial Cells
Jiancheng TANG ; Yue ZHANG ; Ruichen JIANG ; Zhengrong YUE ; Ming LI ; Yaqi ZHANG ; Zetao YIN ; Weiguo WANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(5):131-140
ObjectiveTo investigate the effect of icariin (ICA) on steroid-induced ferroptosis in bone microvascular endothelial cells (BMECs). MethodsRat BMECs were selected and treated with 500 mg·L-1 hydrocortisone for 1.5 h to establish a ferroptosis model of BMECs. The experimental cells were divided into a blank group, hormone group (500 mg·L-1 hydrocortisone), ICA group (500 mg·L-1 hydrocortisone + 34 mg·L-1 ICA), and ferroptosis agonist group (500 mg·L-1 hydrocortisone + 34 mg·L-1 ICA + 2.7 mg·L-1 erastin). Cell viability was detected by CCK-8. The levels of ferrous ion, glutathione (GSH), malondialdehyde (MDA), superoxide dismutase (SOD), and reactive oxygen species (ROS) were detected by related kit species. The ferroptosis-related proteins, such as glutathione peroxidase 4(GPX4), ferritin light chain (FTL), and transferrin receptor protein1 (sTfR) were detected by Western blot, as well as autophagy-related proteins including microtubule-associated protein 1 light chain 3B (LC3B), Beclin1, B-cell lymphoma-2 (Bcl-2), and Caspase-3. Results500 mg·L-1 hydrocortisone intervention for 1.5 h could effectively induce ferroptosis in BMECs, and ferroptosis levels could reach a peak as the intervention continued. In terms of cellular antioxidant capacity, compared with those in the blank group, the cell vitality, GSH in the hormone group decreased significantly, and the levels of ROS, SOD, MDA, and ferrous ions were significantly increased (P<0.01). Compared with those in the hormone group, the cell viability, GSH were significantly increased, and the levels of ROS, SOD, MDA, and ferrous ions were decreased in the ICA group (P<0.01). Compared with those in the ICA group, the cell vitality, GSH in the ferroptosis agonist group decreased significantly, and the levels of ROS, SOD, MDA, and ferrous ions increased significantly (P<0.01). In terms of the relationship between ferroptosis and autophagy, compared with the blank group, the hormone group had significantly increased expression levels of LC3B, sTfR, Beclin1, and FTL and significantly decreased expression levels of GPX4 (P<0.01). Compared with the hormone group, The ICA group had significantly decreased expression levels of LC3B, sTfR, and FTL and significantly increased expression levels of Beclin 1 and GPX4 (P<0.01). Compared with those in the ICA group, the expression levels of LC3B, sTfR, and FTL increased in the rapamycin group, and those of Beclin 1 and GPX4 decreased (P<0.01). In terms of cell ferroptosis and apoptosis,compared with the blank group, the hormone group had significantly increased expression levels of FTL, sTfR and Caspase-3 and significantly decreased expression levels of GPX4, and Bcl-2 (P<0.01). Compared with the hormone group, the ICA group had significantly decreased expression levels of FTL, sTfR and Caspase-3 and significantly increased expression levels of GPX4, and Bcl-2 (P<0.01). Compared with those in the ICA group, the expression levels of FTL, sTfR and Caspase-3 in the ferroptosis agonist group were increased, and the expression levels of GPX4, and Bcl-2 were decreased (P<0.01). In terms of cell function,compared with that in the blank group, the ability of cell migration and tube formation was significantly decreased in the hormone group (P<0.01). Compared with that in the hormone group, the cell migration and tube formation ability in the ICA group were significantly increased (P<0.01). ConclusionFerroptosis is involved in steroid-induced damage in BMECs. ICA can inhibit steroid-induced ferroptosis in BMECs, and the mechanism may be associated with the inhibition of ferroptosis by regulating autophagy.
3.Mechanism of Traditional Chinese Medicine in Treating Steroid-Induced Osteonecrosis of Femoral Head via Regulating PI3K/Akt Pathway: A Review
Yaqi ZHANG ; Bo LI ; Jiancheng TANG ; Ran DING ; Cheng HUANG ; Yaping XU ; Qidong ZHANG ; Weiguo WANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(5):141-149
Steroid-induced osteonecrosis of the femoral head (SONFH) is a severe musculoskeletal disorder often induced by the prolonged or excessive use of glucocorticoids. Characterized by ischemia of bone cells, necrosis, and trabecular fractures, SONFH is accompanied by pain, femoral head collapse, and joint dysfunction, which can lead to disability in severe cases. The pathogenesis of SONFH involves hormone-induced osteoblast apoptosis, bone microvascular endothelial cell (BMEC) apoptosis, oxidative stress, and inflammatory responses. The phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling pathway plays a pivotal role in the development of the disease. Modulating the PI3K/Akt signaling pathway can promote Akt phosphorylation, thereby stimulating the osteogenic differentiation of bone marrow mesenchymal stem cells and osteoblasts, promoting angiogenesis in BMECs, and inhibiting osteoclastogenesis. The research on the treatment of SONFH with traditional Chinese medicine (TCM) has gained increasing attention. Recent studies have shown that TCM monomers and compounds have potential therapeutic effect on SONFH by intervening in the PI3K/Akt signaling pathway. These studies not only provide a scientific basis for the application of TCM in the treatment of SONFH but also offer new ideas for the development of new therapeutic strategies. This review summarized the progress in Chinese and international research on the PI3K/Akt signaling pathway in SONFH over the past five years. It involved the composition and transmission mechanisms of the signaling pathway, as well as its regulatory effects on osteoblasts, mesenchymal stem cells, osteoclasts, BMECs, and other cells. Additionally, the review explored the TCM understanding of SONFH and the application of TCM monomers and compounds in the intervention of the PI3K/Akt pathway. By systematically analyzing and organizing these research findings, this article aimed to provide references and point out directions for the clinical prevention and treatment of SONFH and promote further development of TCM in this field. With in-depth research on the PI3K/Akt pathway and the modern application of TCM, it is expected to bring safer and more effective treatment options for patients with SONFH.
4.Investigation and analysis of the current situation of occupational stress of radiation workers in China
Qi ZHANG ; Jianfei LU ; Peng TONG ; Haoran SUN ; Shanshan KOU ; Xiaolan ZHOU ; ·Yusufu AIKEBAIER ; Weiguo ZHU ; Changsong HOU
Chinese Journal of Radiological Health 2025;34(1):46-54
Objective To investigate and analyze the occupational stress levels and influencing factors among radiation workers in China, and provide a reference for alleviating occupational stress and promoting mental health. Methods Using the general situation questionnaire, Effort-Reward Imbalance questionnaire, and radiation protection knowledge questionnaire, a convenience sampling method was adopted to investigate the occupational stress of 243 radiation workers in Liaoning, Fujian, Guangdong, and Xinjiang provinces. The independent samples t-test, one-way analysis of variance, chi-square test, and binary logistic regression were used to analyze the influencing factors. Results The average score of Effort-Reward Imbalance was 0.97 ± 0.22, and 100 (41.15%) radiation workers had occupational stress. There were significant differences in the detection rate of occupational stress among radiation workers of different ages, working years in radiation positions, monthly incomes, daily sleep durations, and daily working hours (P < 0.05). Logistic regression analysis identified daily working hours as a factor contributing to occupational stress. Conclusion The occupational stress among radiation workers in China is relatively severe. It is recommended to pay attention to the associated risks and implement targeted intervention measures to reduce the impact of occupational stress.
5.Network meta-analysis of non-surgical treatments for foot and ankle ability and dynamic balance in patients with chronic ankle instability
Xinxin ZHANG ; Ke GAO ; Shidong XIE ; Haowen TUO ; Feiyue JING ; Weiguo LIU
Chinese Journal of Tissue Engineering Research 2025;29(9):1931-1944
OBJECTIVE:The optimal non-surgical therapy for chronic ankle instability remains unclear due to the continuous introduction of novel treatment methods despite the availability of several non-surgical options for improving foot and ankle function and dynamic balance in chronic ankle instability patients.This study aims to investigate the most effective non-surgical therapy options to improve foot and ankle function and dynamic balance for patients with chronic ankle instability using a network meta-analysis. METHODS:Using"CAI,exercise,and randomized controlled trial"as search terms,a literature search of PubMed,Embase,Cochrane Library,and Web of Science databases was conducted through a computer network to collect information from the databases from their inception to March 2024 on non-surgical therapies for the treatment of chronic ankle instability randomized controlled trials on foot and ankle function or dynamic balance in patients.EndNote software was utilized for literature management.RevMan 5.4 software and Cochrane Risk of Bias Assessment Tool were used to evaluate the risk of bias of the included literature.Paired meta-analysis and network meta-analysis of the outcomes such as the Foot and Ankle Ability Measure in daily living subscale score,Foot and Ankle Ability Measure in sports activities subscale score,Star Excursion Balance Test-Anterior score,Star Excursion Balance Test-Posteromedial score,Star Excursion Balance Test-Posterolateral score and Cumberland ankle instability tool score were performed using the network commands of Stata 14.0 software.The strength of evidence rating of the outcome metrics was evaluated according to the GRADE Level of Evidence and Strength of Recommendation Grading Criteria. RESULTS:Of the 22 randomized controlled trials that met the inclusion criteria,1 study was rated as low risk,8 studies were rated as medium risk,and 13 studies were rated as high risk,enrolling a total of 952 patients and 25 treatments.(1)Network meta-analysis showed that compared with the control group,Isokinetic Strength Training,Balance Training,Balance+Stroboscopic Glasses Training,Strength Training,Joint Mobilizations Training,CrossFit Training,CrossFit Training+Self-Mobilization,Wobble Board Training,National Academy of Sport Medicine corrective exercise program,Trigger Point Dry Needling,and Neuromuscular Training had different significant enhancement effects on improving foot and ankle function and dynamic balance in patients with chronic ankle instability(P<0.05).(2)Cumulative probability ranking results showed that the three treatments with the highest ranked Cumberland ankle instability tool score were Joint Mobilizations Training(88.6%)>Visual Feedback Balance Training(83.1%)>CrossFit Training+Self-Mobilization(74.8%);the three treatments with the highest ranked Star Excursion Balance Test-Anterior score were Joint Mobilizations Training(88.4%)>Isokinetic Strength Training(86.9%)>National Academy of Sport Medicine corrective exercise program(65.0%);the three treatments with the highest ranked Star Excursion Balance Test-Posteromedial score were Balance+Stroboscopic Glasses Training(87.4%)>Neuromuscular Training(74.6%)>Strength Training(68.9%);the three treatments with the highest ranked Star Excursion Balance Test-Posterolateral score were CrossFit Training+Self-Mobilization(74.6%)>Balance+Stroboscopic Glasses Training(70.0%)>Neuromuscular Training(63.7%);the three treatments with the highest ranked Foot and Ankle Ability Measure in daily living subscale score were National Academy of Sport Medicine corrective exercise program(91.9%)>Balance+Stroboscopic Glasses Training(85.6%)>Wobble Board Training(82.2%);the three treatments with the highest ranked Foot and Ankle Ability Measure in sports activities subscale score were Balance+Stroboscopic Glasses Training(93.5%)>Balance Training(86.7%)>National Academy of Sport Medicine corrective exercise program(86.4%). CONCLUSION:Non-surgical therapies can significantly improve foot and ankle function and dynamic balance in patients with chronic ankle instability.National Academy of Sport Medicine corrective exercise program had the best efficacy in improving foot and ankle daily activity function in chronic ankle instability patients;Balance+Stroboscopic Glasses Training had the best efficacy in improving foot and ankle sports function and posterior medial dynamic balance;Joint Mobilizations Training had the best efficacy in improving anterolateral dynamic balance and ankle instability condition;and CrossFit Training+Self-Mobilization had the best efficacy in improving posterior lateral dynamic balance.The strength of evidence for each outcome was low,influenced by the risk of methodological bias and risk of publication bias of the included studies.Therefore,the above conclusions need to be validated by more high-quality pilot studies.
6.Exploration and Reflection on the Construction of Pre-admission Processes in Public Hospitals
Guojie ZHANG ; Hongmei ZHANG ; Qinghua BAI ; Liluan YOU ; Wei ZHANG ; Xueqin SUN ; Jinjin GAO ; Zheng CHEN ; Weiguo ZHU ; Qing CHANG
Medical Journal of Peking Union Medical College Hospital 2025;16(5):1185-1192
Pre-admission is a critical initiative to optimize medical service processes and alleviate the challenge of "difficult access to healthcare. "However, there is currently a lack of standardized protocols for pre-admission procedures. This study aims to systematically analyze key nodes and risk factors in pre-admission process design and propose optimization strategies, providing a foundation for policy formulation and hospital practices. By constructing a "forward-reverse" dual-process model of pre-admission and identifying risk points based on stakeholder theory (patients, hospitals, healthcare administration, and insurance), the study reveals that while pre-admission can reduce the average length of stay, improve bed turnover rates, and enhance patient satisfaction, it also presents risks such as cross-period financial settlement, challenges in insurance policy adaptability, demands for information system integration, and the need for defining medical safety boundaries. To optimize the pre-admission process and mitigate these risks, this study explores framework improvements in areas including eligibility criteria, mode selection, cost settlement, transition between pre-admission and inpatient status, and cancellation of pre-admission, offering practical guidance for public hospitals. The authors argue that pre-admission requires tripartite collaboration among hospitals, insurers, and healthcare administrations: hospitals should establish top-level design, continuously refine processes, and implement dynamic risk assessment mechanisms; insurance providers should support cross-period settlement policies; and healthcare administrations should issue guiding policies or standardized protocols. Through multi-department coordination and collaborative efforts, the optimization and innovation of pre-admission processes can be advanced, ultimately delivering more efficient and convenient healthcare experiences for patients.
7.Role of Wnt signaling Pathway in Diabetic Osteoporosis and Traditional Chinese Medicine Intervention: A Review
Yaqi ZHANG ; Weiguo WANG ; Qidong ZHANG ; Huizhong BAI ; Lingling QIN ; Feng GAO
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(9):283-292
Diabetic osteoporosis (DOP) is a kind of bone complication caused by diabetes, which is characterized by the decrease of bone mineral density, the change of bone microstructure and the increase of bone fragility. The process of DOP is closely related to high glucose, insulin resistance, oxidative stress and other mechanisms. The Wnt/β-catenin signaling pathway plays an important role in mediating insulin resistance and bone metabolic balance in diabetes. Regulation of Wnt signal transduction promotes the expression of glycogen synthase kinase-3β(GSK-3β)phosphorylation and improves glucose and lipid metabolism. The Wnt/β-catenin signaling pathway is also an important way regulating osteocyte-driven bone remodeling, which not only plays an important regulatory role in the balance between osteoblasts and osteoclasts and improve bone metabolic homeostasis, but also promotes the expression of osteopontin, osteocalcin and type Ⅰ collagen, and improves bone proliferation and osteogenic differentiation by regulating the Wnt pathway. In recent years, the research of traditional Chinese medicine (TCM) in the prevention and treatment of DOP has gradually increased, and the exploration of TCM to interfere with the Wnt pathway to improve DOP has made some progress. This paper collects and summarizes the studies on the Wnt signaling pathway in glucose metabolism, bone metabolism and DOP worldwide in the past decade, as well as the related literature on the intervention of DOP by TCM compounds (classical and other compounds), single Chinese medicine and TCM monomers based on the Wnt pathway, in order to provide a reference and direction for the development of new drugs for clinical prevention and treatment of DOP.
8.Dose conversion coefficients for humans after oral administration of urea-14C
Zhen ZHANG ; Guangyi TANG ; Zhongjian MA ; Weiguo ZHU ; Fei CHEN
Chinese Journal of Radiological Health 2024;33(2):153-157
Objective To calculate the absorbed doses and conversion coefficients of various organs in humans after oral administration of urea-14C, and to provide a convenient method for evaluating the internal radiation dose caused by ingestion of urea-14C in Chinese population. Methods The Chinese reference human voxel model was imported into the FLUKA software to simulate the absorbed doses to organs under internal exposure to 14C, and to obtain the dose conversion coefficients for oral administration of urea-14C. Results The absorbed dose conversion coefficients for the stomach, colon, bladder, heart, and muscles were 0.029, 0.029, 0.32 (0.24), 0.028, and 0.029 mGy/MBq in negative cases, and 0.079, 0.078, 0.18 (0.15), 0.076, and 0.080 mGy/MBq in positive cases. The committed effective dose coefficients were 0.041 (0.037) mSv/MBq in negative cases and 0.082 (0.081) mSv/MBq in positive cases. Conclusion The dose conversion coefficients obtained in this study can provide important parameters for evaluating the absorbed dose to Chinese population after oral administration of urea-14C.
9.Research progress on targeted protein S-palmitoylation modification in T cell immunotherapy
Liting SUN ; Weiguo ZHANG ; Yue TONG
Journal of China Pharmaceutical University 2024;55(1):45-52
Abstract: S-palmitoylation, a reversible and dynamic post-translational modification in cells, is involved in regulating the transcription and expression of downstream target genes as well as signal transduction, thereby affecting cell life activities. Studies have shown that thousands of human proteins undergo S-palmitoylation modification, suggesting that S-palmitoylation is closely related to the progression and treatment of diseases. T cells play central roles in anti-tumor immune responses. A variety of T cell immune-related proteins are regulated by S-palmitoylation. In the present study, we focus on the impact of S-palmitoylation on T cell signal transduction and its application in T cell immunotherapy, aiming to provide new ideas for the development of new targets and peptide inhibitors for T cell immunotherapy.
10.Diagnostic value of energy spectrum CT quantitative parameters combined with serum TSHR-mRNA for papillary thyroid microcarcinoma
Weiguo ZHANG ; Jiaping LIU ; Xiangnan LI ; Jiyang ZHANG
Journal of Practical Radiology 2024;40(1):27-31
Objective To explore the diagnostic value of energy spectrum CT quantitative parameters combined with serum thy-roid stimulating hormone receptor-messenger ribonucleic acid(TSHR-mRNA)for papillary thyroid microcarcinoma(PTMC).Methods A total of 105 patients with thyroid micronodules confirmed by surgery and pathology were collected,61 of whom were PTMC(PTMC group),and 44 patients with micronodular goiter(MNG)(MNG group).Energy spectrum CT quantitative parameters and serum TSHR-mRNA expression were compared between the two groups.The diagnostic value of energy spectrum CT quantitative parame-ters alone and combined with serum TSHR-mRNA for PTMC was analyzed by receiver operating characteristic(ROC)curve.Results The iodine concentration and slope of energy spectrum CT quantitative parameters between PTMC group and MNG group were signifi-cantly different in plain scan,arterial and venous phases(P<0.05).The mean serum TSHR-mRNA expression in the PTMC group was higher than that in MNG group(P<0.05).The area under the curve(AUC)for diagnosing PTMC using quantitative parame-ters of energy spectrum CT combined with serum TSHR-mRNA was 0.913,and the accuracy,sensitivity,and negative predictive value of diagnosing PTMC were significantly higher than those of quantitative parameters of energy spectrum CT or serum TSHR-mRNA(P<0.05).Conclusion Both energy spectrum CT quantitative parameters and serum TSHR-mRNA can be used to diagnose PTMC alone,and the combination of both is more accurately.

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