1.Mechanism of Zuoguiwan in Inhibiting Osteoclast Activation Induced by Breast Cancer via Regulating p38 MAPK/ERK Signaling Pathway
Jianjiang FU ; Yinlong MEI ; Junchao MA ; Xiaocui ZHU ; Wei WANG ; Hong LYU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(1):1-9
ObjectiveTo investigate the effects of Zuoguiwan on osteoclast activation induced by breast cancer and its mechanism. MethodsTo simulate breast cancer-induced osteoclastic bone metastasis, RAW264.7 cells were cultured in conditioned medium containing 50% supernatant of MDA-MB-231 breast cancer cells. The dosages of Zuoguiwan used in the experiment were sera containing 5% and 10% Zuoguiwan. Tartrate-resistant acid phosphatase (TRAP) staining was used to detect osteoclast activation. Enzyme-linked immunosorbent assay (ELISA) was used to measure Cathepsin K secretion from RAW264.7 cells. Real-time quantitative polymerase chain reaction (PCR) was used to detect the mRNA expression levels of osteocalcin (OCN) and bone sialoprotein (BSP). Immunoprecipitation was employed to detect the interaction between Runt-related transcription factor 2 (Runx2) and core binding factor β subunit (CBF-β). Western blot was used to assess the protein expression of Runx2, phosphorylated Runx2 (p-Runx2), extracellular signal-regulated kinases 1/2 (ERK1/2), p-ERK1/2, p38 mitogen-activated protein kinase (MAPK), p-p38 MAPK, and CBF-β. ResultsCompared with the blank group, the MDA-MB-231 cell supernatant group showed a significant increase in TRAP-positive cell counts and Cathepsin K secretion. Meanwhile, the expression levels of p-Runx2, Runx2-CBF-β interaction, BSP and OCN mRNA, p-p38 MAPK, and p-ERK1/2 proteins were significantly decreased (P<0.01). Compared with the MDA-MB-231 cell supernatant group, Zuoguiwan-containing sera significantly reduced TRAP-positive cell counts and Cathepsin K secretion (P<0.01), significantly increased p-Runx2, BSP and OCN mRNA expression, as well as p-p38 MAPK and p-ERK1/2 protein levels, and promoted the interaction between Runx2 and CBF-β (P<0.01). No significant change in Runx2 expression was observed. Compared to the blank group, the BVD-523 group showed significantly lower expression of p-p38 MAPK and p-ERK1/2 proteins (P<0.01). Compared with the BVD-523 group, both low and high concentration Zuoguiwan-containing sera groups showed significantly higher p-p38 MAPK expression (P<0.01), and the high concentration Zuoguiwan group also exhibited a significant increase in p-ERK1/2 expression (P<0.01), while no statistical difference was found in the low-dose group. ConclusionZuoguiwan inhibits osteoclast activation by inducing phosphorylation of the key transcriptional regulator Runx2 in intra-osteoclast bone formation, and this process is closely associated with the activation of the p38 MAPK/ERK signaling pathway.
2.Effect of Qingxin Jieyu Granules on Artery Thrombosis and Akt/NF-κB Signaling Pathway in EA.hy926 Cells Exposed to TNF-α
Chenchen HE ; Chenyi WEI ; Zhenghao LYU ; Qiaoyan CAI ; Zhuye GAO ; Ling ZHANG ; Jianfeng CHU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(3):89-97
ObjectiveTo observe the effects of Qingxin Jieyu granules (QXJYG) on FeCl3-induced carotid artery thrombosis in rats and on the expression of thrombosis-related proteins tissue factor (TF) and tissue factor pathway inhibitor (TFPI) as well as the protein kinase B (Akt)/nuclear factor-κB (NF-κB) signaling pathway in EA.hy926 cells exposed to tumor necrosis factor-α (TNF-α), thus preliminarily exploring the mechanism of QXJYG in inhibiting thrombosis. MethodsThirty-six SD rats were randomized into normal control, model, positive control (aspirin, 9 mg·kg-1), and low-, medium-, and high-dose (0.99, 1.98, 3.96 g·kg-1, respectively) QXJYG groups (n=6). The rats in the drug treatment groups were administrated with corresponding drugs, and those in the normal control group and model group were given an equal volume of distilled water. After 14 consecutive days of prophylactic gavage, the rat model of common carotid artery thrombosis was established with 45% FeCl3 solution, and the blood vessels were collected and the wet weight of thrombus was weighed by an electronic balance (precision of 1/10 000). The thrombosis in the common carotid artery of each group of rats was observed by hematoxylin-eosin staining. The plasma levels of von Willebrand factor (vWF), platelet endothelial cell adhesion molecule-1 (PECAM-1), tissue-type plasminogen activator (t-PA), and plasminogen activator inhibitor-1 (PAI-1) were determined by enzyme-linked immunosorbent assay. An endothelial cell injury model was established by treating EA.hy926 human umbilical vein endothelial cells with TNF-α. The cell counting kit-8 method was used to screen the intervention concentrations of QXJYG. Western blot was employed to determine the protein levels of TF, TFPI, Akt, p-Akt, NF-κB p65, and p-NF-κB p65 in each group of cells. ResultsThe animal experiment showed that compared with the normal control group, the model group showed an increase in carotid artery thrombus weight (P<0.05), with unclear vascular structure and extensive thrombosis in the lumen. In addition, the plasma levels of vWF, PECAM-1, and PAI-1 were elevated, while the t-PA level became lowered (P<0.05) in the model group. Compared with the model group, the aspirin and QXJYG groups showed reductions in the weight of FeCl3-induced carotid artery thrombi (P<0.05) and thrombosis in the lumen, declines in plasma levels of PECAM-1 and PAI-1, and an elevation in the t-PA level (P<0.05). Moreover, the QXJYG groups showed reductions in the plasma level of vWF (P<0.05), which, however, had no significant difference between the aspirin group and the model group. The cell experiments indicated that 31.25, 62.5, 125, 250, 500 mg·L-1 QXJYG had no effect on the viability of EA.hy926 cells. Therefore, 250, 500 mg·L-1 QXJYG were selected as the intervention concentrations for subsequent experiments. Western blotting results showed that compared with the control group, the TNF-α stimulation downregulated the expression of TFPI (P<0.05), upregulated the expression of TF, and increased the ratios of p-Akt/Akt and p-NF-κB p65/NF-κB p65 (P<0.05) in EA.hy926 cells. Compared with the model group, the intervention with QXJYG upregulated the expression of TFPI (P<0.05), inhibited the expression of TF, and decreased the ratios of p-Akt/Akt and p-NF-κB p65/NF-κB p65 (P<0.05). ConclusionQXJYG has the effect of inhibiting thrombosis and regulating the expression of TF and TFPI in endothelial cells exposed to TNF-α by suppressing the abnormal activation of the Akt/NF-κB signaling pathway.
3.Syndrome Differentiation and Treatment of Atrial Fibrillation based on the Holistic View of "Spleen-Vessels-Heart-Spirit"
Yihang DU ; Chenglin DUAN ; Xueping ZHU ; Meng LYU ; Jiafan CHEN ; Yi WEI ; Yuanhui HU
Journal of Traditional Chinese Medicine 2025;66(1):89-92
Based on the holistic view of "spleen-vessels-heart-spirit" system, this article explores the pathogenesis and progression of atrial fibrillation. It is proposed that the onset of atrial fibrillation is due to failure of the spleen to transport and disharmony of blood vessels; phlegm and blood stasis obstructing the collaterals and damage to the heart structure are the basis of its pathogenesis; the unclear mind and disorder of body and spirit are the causes of its progression. Based on the characteristics of pathological changes in different stages of the disease, it is proposed that early treatment should focus on restoring the middle jiao, clearing and promoting blood vessels, using modified Yigong Powder (异功散); during the progression of the disease, treatment should remove blood stasis and phlegm, nourish heart and protect the pulse, using self-prescribed modified Mengshi Tongmai Decoction (礞石通脉汤); meanwhile, calming mind and stabilizing palpitations, and regulating spirit should be sequentially incorporated, with self-prescribed Jiazao Ningmai Decoction (甲枣宁脉汤) or Shenying Dingji Decoction (参英定悸汤) and modified as appropriate. Clinical treatment should focus on the whole disease course of atrial fibrillation, implementing stage-based treatments to enable early intervention and holistic regulation.
4.Clinical Observation of Modified Zhigancao Tang in Treating Patients with Liver and Kidney Deficiency of Parkinson's Disease and Its Effect on Neuronal Signal-related Proteins
Yifo WEI ; Furong LYU ; Jia YAO ; Guonian LI ; Xianyi LUO ; Meng LUO ; Zhengzheng WEN ; Qiuqi LI ; Yihan LIU ; Linlin YANG ; Rui ZUO ; Wenxin DANG ; Fang MI ; Xiaoyan WANG ; Zhigang CHEN ; Fan LIU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(4):166-173
ObjectiveMicrotube associated protein-2 (MAP-2), alpha-tubulin (α-tubulin), and synaptophysin (SYP) are important proteins in neuronal signal communication. This paper observed the effects of modified Zhigancao Tang on the expression of serum α-Synuclein (α-Syn) and its oligomers, MAP-2, α-tubulin, and SYP of patients with liver and kidney deficiency of Parkinson's disease (PD), analyzed their correlation, and evaluated the therapeutic effect of modified Zhigancao Tang in patients with liver and kidney deficiency of PD based on α-Syn transmission pathway mediated by neuronal communication in vivo. MethodsA total of 60 patients with PD who met the inclusion criteria were randomly divided into a treatment group (30 cases) and a control group (30 cases). Both groups were treated on the basis of PD medicine, and the treatment group was treated with modified Zhigancao Tang. Both groups were treated for 12 weeks. The changes in UPDRS score, TCM syndrome score, and expression of serum α-Syn and its oligomers, MAP-2, α-tubulin, and SYP were observed before and after 12 weeks of treatment in each group. The correlation between the above-mentioned serum biological indexes and the levels of serum α-Syn and its oligomers was analyzed. ResultsAfter treatment, the TCM syndrome score, UPDRS score, UPDRS-Ⅱ score, and UPDRS-Ⅲ score of the treatment group were significantly decreased (P<0.05, P<0.01). The UPDRS score, UPDRS-Ⅱ score, and UPDRS-Ⅲ scores in the treatment group were significantly decreased compared with those in the control group after treatment (P<0.05). After treatment, the total effective rate of the control group was 63.3% (19/30), and that of the treatment group was 86.7% (26/30). The clinical effect of the observation group was better than the control group (Z=-2.03, P<0.05). The total effective rate of the observation group was better than that of the control group, and the difference was statistically significant (χ2=5.136, P<0.05). After treatment, the oligomer level of serum α-Syn and MAP-2 level in the treatment group were significantly decreased (P<0.05, P<0.01). The levels of serum α-Syn and its oligomers, as well as α-tubulin in the treatment group, were significantly decreased compared with those in the control group after treatment (P<0.05, P<0.01). Serum α-Syn was correlated with serum MAP-2 and α-Syn oligomer in patients with PD (P<0.05, P<0.01) but not correlated with serum SYP . Serum α-Syn oligomers of patients with PD were correlated with serum MAP-2 and α-tubulin (P<0.05, P<0.01) but not correlated with serum SYP level. Serum SYP of patients with PD was correlated with serum MAP-2 (P<0.05). ConclusionModified Zhigancao Tang has a therapeutic effect on patients with liver and kidney deficiency of PD by inhibiting the production of α-Syn oligomers and intervening α-Syn microtubule transport pathway in vivo.
5.Textual Research of Key Information of Classic Formula Xieqingwan Based on Ancient and Modern Literature
Yujie CHANG ; Lyuyuan LIANG ; Jialei CAO ; Xinghang LYU ; Wenxi WEI ; Xiaofang WANG ; Huizhen ZHANG ; Sai REN ; Mengqi WANG ; Bingqi WEI ; Bingxiang MA
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(4):226-234
ObjectiveThis paper aims to systematically collect and organize ancient and modern clauses and studies containing Xieqingwan, excavate and analyze the key information of Xieqingwan, and provide a reference for facilitating the development of the classic formula Xieqingwan. MethodsThe composition, dosage, decocting methods, usage, and other key information of Xieqingwan in ancient traditional Chinese medicine books were collected and analyzed by means of literature research and metrological methods. The modern clinical application of Xieqingwan was summarized. ResultsA total of 42 pieces of effective data involving 32 ancient traditional Chinese medicine books were collected. Xieqingwan was first recorded in Xiaoer Yaozheng Zhijue. The drug origin of this formula is basically clear in the ancient traditional Chinese medicine books. The modern drug usage and decocting method were as follows: Angelicae Sinensis Radix, Gentianae Radix et Rhizoma, Chuanxiong Rhizoma, Gardenia seeds, Radix et Rhizoma Rhei, Notopterygii Rhizoma et Radix, and Saposhnikoviae Radix were grounded to fine powder, decocted with honey, and finally formed into pills with the size of a chicken head (1.5 g). It was suggested that half a pill or one pill were taken for one dose with warm Lophatheri decoction and sugar. The indications and clinical application had developed from the recordings in Xiaoer Yaozheng Zhijue and evolved from pediatrics to ophthalmic otolaryngology, neurology, dermatology, digestion, and respiratory diseases. The main pathogenesis of these diseases is heat in the liver meridian and is treated. The effect of Xieqingwan is "clearing away heat and toxicity, removing fire and relaxing the bowels, and dispersing swelling and relieving pain". It is recommended to use the corresponding preparation methods in the 2020 Edition of Pharmacopoeia of the People's Republic of China. Modern clinical studies are centered around the clinical application of Xieqingwan, which is often modified and used in treating Tourette syndrome, herpes, febrile convulsion, sleepwalking, and insomnia. ConclusionThis paper conducts a thorough textual research of the key information of Xieqingwan, induces its historic evolution, and confirms its key information, so as to provide a reference for the future development of Xieqingwan.
6.Textual Research and Analysis of Historic Origin and Ancient and Modern Application of Classic Formula Shengjiangsan
Lyuyuan LIANG ; Jialei CAO ; Xinghang LYU ; Weixiao LI ; Wenxi WEI ; Bingqi WEI ; Zhe WANG ; Yiping WANG ; Bingxiang MA ; Wenli SHI
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(9):219-227
Shengjiangsan is a classic formula for treating warm diseases with wide clinical application and accurate efficacy. There are different opinions on the origin of this formula and lacks key information research on this formula. Therefore, in this study, we conducted systematic research into the historic origin, composition, and other key information of this Shengjiangsan. Results showed that Shengjiangsan has different versions, with "Neixian Fufang", "Jiawei Jianghuangwan", "Peizhensan", and "Taijiwan" being the same formula with different names. Shengjiangsan was first recorded as "Neixian Fufang" in Wanbing Huichun written by GONG Tingxian from the Ming dynasty, inherited and developed by YANG Lishan from Qing dynasty, and has been passed down to modern times. Pills and powder are two main forms of Shengjiangsan, and powder has become more popular nowadays. According to the measurement system of Ming and Qing dynasties, the recommended dosage and usage of Shengjiangsan are as follows. For the pill version of Shengjiangsan, Bombyx Batryticatus of 74.6 g, Curcumae Longae Rhizoma of 9.325 g, Cicadae Periostracum of 9.325 g, and Rhei Radix et Rhizoma of 149.2 g were processed into pills for preparation. Single dosage is Bombyx Batryticatus of 1.15 g, Curcumae Longae Rhizoma of 0.14 g, Cicadae Periostracum of 0.14 g, and Rhei Radix et Rhizoma of 2.3 g, with halved dosage applied for children. For the powder version of Shengjiangsan, the dosage varied in accordance with the severity of the disease. Bombyx Batryticatus of 1.84 g, Curcumae Longae Rhizoma of 0.28 g, Cicadae Periostracum of 0.92 g, and Rhei Radix et Rhizoma of 3.68 g were processed into powder for patients with mild symptoms. Bombyx Batryticatus of 2.48 g, Curcumae Longae Rhizoma of 0.37 g, Cicadae Periostracum of 1.23 g, and Rhei Radix et Rhizoma of 4.91 g were processed into powder for patients with severe symptoms. Bombyx Batryticatus of 3.68 g, Curcumae Longae Rhizoma of 1.84 g, Cicadae Periostracum of 0.55 g, and Rhei Radix et Rhizoma of 7.36 g were processed into powder for patients with critical conditions. In this formula, four herbs were ground to fine powder. For patients with mild symptoms, the whole formula was divided into four dosages, and each dosage weighed 6.71 g. The 200 mL yellow rice wine and 18.65 g honey were added, and the solution was stirred and taken cold till full recovery. For patients with severe symptoms, the whole formula was divided into three dosages, and each weighed 8.95 g. 300 mL yellow rice wine and 27.98 g honey were added, and the solution was stirred and taken cold. For patients with critical conditions, the whole formula was divided into two dosages, and each weighed 13.43 g. 400 mL yellow rice wine and 37.3 g honey were added, and the solution was stirred and taken cold. Shengjiangsan has the effect of ascending lucidity and descending turbidity, dissipating wind, and clearing heat. It is specialized in treating severe heat in exterior, interior, and triple energizers in warm diseases and has a wide modern clinical application. In this study, the historic evolution and key information of Shengjiangsan were reviewed and analyzed, and the key information table of Shengjiangsan was attached, serving as a reference for scholars' research and a theoretical basis for its market transformation.
7.Organizational Readiness for Change and Factors Influencing the Implementation of Shared Medical Appointment for Diabetes in Primary Healthcare Institutions
Wei YANG ; Yiyuan CAI ; Jiajia CHEN ; Run MAO ; Lang LINGHU ; Sensen LYU ; Dong XU
Medical Journal of Peking Union Medical College Hospital 2025;16(2):479-491
The success of implementation research is closely tied to the institution's pre-implementation readiness. This study aims to explore the organizational readiness for change (ORC) and its influencing factors on primary healthcare settings in the implementation of the "Shared Medical Appointment for Diabetes (SMART) in China: design of an optimization trial" and to enhance ORC and provide insights to support the effective implementation of the program. Qualitative interviews and quantitative surveys were conducted to evaluate the ORC level and its influencing factors in 12 institutions implementing the SMART program. The Scale for Assessing the Institution's Readiness to Implement Evidence-Based Practices was utilized to measure ORC levels. Qualitative interviews were conducted among change implementers to gather information regarding the status of influencing factors. Thematic analysis was applied to extract factors from the interview data, and an assessment questionnaire was developed to measure the perceived impact of these factors. A fuzzy-set qualitative comparative analysis (fsQCA) method was employed to identify the influencing factors of ORC and pathways leading to high-level ORC. Seventy implementers from 12 institutions, encompassing administrators, clinicians, and health managers, participated in the interviews and surveys. The median and interquartile of the ORC scores were 105.20 (101.23, 107.33). The fsQCA indicated that a clear understanding of specific tasks and responsibilities, the active engagement of key participants, sufficient preliminary preparation, and the use of audits and feedback mechanisms were critical pathways to a high-level ORC. Conversely, institutions lacking key participants, preliminary preparation, or marginal influence demonstrated a low-level ORC. Before implementing innovation, Coherence and Cognitive Participation were identified as critical factors in influencing ORC. Strong leadership from key participants played pivotal role in enhancing readiness for change and was essential for improving implementation fidelity and overall program success.

Result Analysis
Print
Save
E-mail