1.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.
2.Textual Research on Key Information of Classic Formula Houpo Qiwutang and Its Ancient and Modern Applications
Jinlong ZHANG ; Wei CHEN ; Ruobing LI ; Baikun YIN ; Yaodong GU ; Jun LEI ; Xicheng JIANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(3):213-222
Houpo Qiwutang originated from the Synopsis of the Golden Chamber, and it consists of seven medicines: Magnoliae Officinalis Cortex, Rhei Radix et Rhizoma, Aurantii Fructus Immaturus, Cinnamomi Ramulus, Zingiberis Rhizoma Recens, Glycyrrhizae Radix et Rhizoma, and Jujubae Fructus. It is a basic formula for the treatment of abdominal fullness. Through the bibliometric method, the historical history, drug base, preparation and dosage, decoction method, and ancient and modern applications of Houpu Qiwu Tang were analyzed by means of textual research. The research finds that Houpu Qiwu Tang has been passed down through the generations in an orderly manner with fewer changes. The drug base of this formula is basically clear, and the base of Magnoliae Officinalis Cortex, Rhei Radix et Rhizoma, Cinnamomi Ramulus, Zingiberis Rhizoma Recens, and Jujubae Fructus is consistent with the 2020 edition of Chinese Pharmacopoeia. The mainstream base of Aurantii Fructus Immaturus is the dried young fruit of Citrus aurantium of Rutaceae family, and the historical mainstream base of Glycyrrhizae Radix et Rhizoma is the dried root of Glycyrrhiza uralensis of Leguminosae family. The modern dosage of this formula is 110.40 g of Magnoliae Officinalis Cortex, 41.40 g of Rhei Radix et Rhizoma, 69 g of Aurantii Fructus Immaturus, 27.60 g of Cinnamomi Ramulus, 69 g of Zingiberis Rhizoma Recens, 41.40 g of Glycyrrhizae Radix et Rhizoma, and 30 g of Jujubae Fructus. In addition, the decoction method is to add 2 000 mL of water with the above seven flavors of the medicine, boil it to 800 mL, and then take 160 mL in a warm state each time. The amount of the medicine taken for each time is 22.08 g of Magnoliae Officinalis Cortex, 8.28 g of Rhei Radix et Rhizoma, 13.80 g of Aurantii Fructus Immaturus, 5.52 g of Cinnamomi Ramulus, 13.80 g of Zingiberis Rhizoma Recens, 8.28 g of Glycyrrhizae Radix et Rhizoma, and 6 g of Jujubae Fructus. The modern application of this formula involves the digestive system, respiratory system, and urinary system. It is more advantageous in digestive system diseases such as early postoperative inflammatory bowel obstruction, functional dyspepsia, gastric pain, functional abdominal distension, and gastric reflux esophagitis. By comprehensively examining the key information of Houpu Qiwu Tang, this paper aims to provide literature support for the development and clinical application of this formula.
3.Differentiation and Treatment of Lipid Turbidity Disease Based on Theory of "Spleen Ascending and Stomach Descending"
Yun HUANG ; Wenyu ZHU ; Wei SONG ; Xiaobo ZHANG ; Xin ZHOU ; Lele YANG ; Tao SHEN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(3):244-252
Lipid turbidity disease is a metabolic disease featuring lipid metabolism disorders caused by many factors such as social environment, diet, and lifestyle, which is closely related to many diseases in modern medicine, such as hyperlipidemia, obesity, fatty liver, atherosclerosis, metabolic syndrome, and cardiovascular and cerebrovascular diseases, with a wide range of influence and far-reaching harm. According to the Huangdi Neijing, lipid turbidity disease reflects the pathological change of the body's physiologic grease. Grease is the thick part of body fluids, which has the function of nourishing, and it is the initial state and source of important substances in the human body such as brain, marrow, essence, and blood. Once the grease of the human body is abnormal, it can lead to lipid turbidity disease. The Huangdi Neijing also points out the physiological relationship between the transportation and transformation of body fluids and the rise and fall of the spleen and stomach, which can deduce the pathological relationship between the occurrence of lipid turbidity disease and the abnormal rise and fall of the spleen and stomach functions. Lipid turbidity disease is caused by overconsumption of fatty and sweet foods or insufficient spleen and stomach endowments, leading to disorders of the function of promoting clear and reducing turbidity in the spleen and stomach. This leads to the transformation of thick grease in body fluids into lipid turbidity, which accumulates in the body's meridians, blood vessels, skin pores, and organs, forming various forms of metabolic diseases. The research team believed that the pathological basis of lipid turbidity disease was the abnormal rise and fall of the spleen and stomach and the obstruction of the transfer of grease. According to the different locations where lipid turbidity stays, it was divided into four common pathogenesis types: ''inability to distinguish between the clear and turbid, turbid stagnation in the Ying blood'', ''spleen not rising clear, turbid accumulation in the vessels'', ''spleen dysfunction, lipid retention in the pores'', ''spleen failure to transportation and transformation, and grease accumulation in the liver''. According to the pathogenesis, it could be divided into four common syndromes, namely, turbid stagnation in the Ying blood, turbid accumulation in the vessels, lipid retention in the pores, and grease accumulation in the liver, and the corresponding prescriptions were given for syndrome differentiation and treatment, so as to guide clinical differentiation and treatment of the lipid turbidity disease.
4.Traditional Chinese Medicine Treats Diabetic Nephropathy via Pathways Related to Pyroptosis: A Review
Jintao SHI ; Zhiyi ZHANG ; Yunfei WEI ; Jiarui HAN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(3):290-300
Diabetic kidney disease (DKD), one of the leading causes of end-stage renal disease, shows increasing prevalence and mortality, seriously affecting the physical and mental health of patients. As a crucial link in the occurrence and development of DKD, pyroptosis can lead to kidney cell injury and inflammation through the abnormal activation of reactive oxygen species (ROS)/thioredoxin-interacting protein (TXNIP)/NOD-like receptor protein 3 (NLRP3), Toll-like receptor 4 (TLR4)/nuclear factor-κB (NF-κB)/NLRP3, nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1), mitogen-activated protein kinase (MAPK)/NLRP3, and hypoxia-inducible factor-1α (HIF-1α)/NLRP3 signaling pathways, which accelerate the progression of DKD. In recent years, traditional Chinese medicine (TCM) has demonstrated definite efficacy in the treatment of DKD via multiple targets and pathways. Studies have shown that various TCM active components, including glycosides, flavonoids, polyphenols, terpenoids, and alkaloids, as well as TCM compound prescriptions for clearing heat and detoxifying, tonifying deficiency and consolidating root, and eliminating stasis and descending turbidity, can target relevant signaling pathways to inhibit pyroptosis and intervene in the development of DKD, providing new possibilities for precision treatment of DKD. This article systematically reviews the relevant pathways of pyroptosis and summarizes the research achievements and mechanisms of TCM active components and compound prescriptions in the treatment of DKD via pyroptosis in recent years. This review aims to provide new directions and ideas for the treatment and research of DKD with TCM and promote the modernization and development of TCM.
5.The Effect of Qishao Tongbi Capsule (芪芍通痹胶囊) on the Wnt/β-catenin Pathway in a Rat Model of Intervertebral Disc Degeneration
Yumen XUE ; Xilin XU ; Wei HAN ; Jiaben XU ; Wenting XU ; Zelin LIU ; Xiaofeng ZHANG
Journal of Traditional Chinese Medicine 2025;66(1):79-88
ObjectiveTo explore the possible mechanism of Qishao Tongbi Capsule (芪芍通痹胶囊, QTC) in the treatment of intervertebral disc degeneration (IDD). MethodsSeventy-five rats were randomly divided into control group, model group, low-dose QTC group, high-dose QTC group, high-dose QTC +agonist group, with 15 rats in each group. Except for the control group, all other groups were subjected to a fibrous ring puncture to prepare an IDD model. After modeling, rats in low-dose QTC group and high-dose QTC group were given QTC at doses of 0.2 and 0.8 g/(kg·d) by gavage, respectively. Rats in high-dose QTC+ agonist group was given QTC at 0.8 g/(kg·d) and SKL2001 solution at 10 mg/(kg·d) by gavage. The control group and model group were given 10 ml/(kg·d) distilled water by gavage. All treatments were given once a day for 4 consecutive weeks. After treatment, X-ray and magnetic resonance imaging (MRI) were used to detect IDD degree. Hematoxylin-eosin (HE) staining and Safranin O-Fast Green staining were used to observe the morphological changes of the intervertebral disc tissue. Immunohistochemical staining was performed to examine the levels of proteoglycan, type Ⅱ collagen (COL Ⅱ), and matrix metalloproteinase-3 (MMP-3) in the intervertebral disc tissue. Western blotting was used to detect the extracellular matrix (ECM)-related proteins (proteoglycan, COL Ⅱ, MMP-3, MMP-9, MMP-13), aging-related proteins (P53, P21, P16), apoptosis related proteins, including B-cell lymphoma/leukemia 2 (BCL-2), BCL-2 related X protein (BAX), Cleaved Caspase-3, and Wnt/β-catenin pathway related proteins such as Wnt3a, glycogen synthase kinase-3β (GSK-3β) and β-catenin in the intervertebral disc nucleus pulposus (NP) tissue. Reverse Transcription Quantitative Polymerase Chain Reaction (RT-qPCR) was used to assess the mRNA expression of Wnt3a, GSK-3β, and β-catenin in intervertebral disc tissue. ResultsCompared with the model group, rats in the low-dose QTC group and high-dose QTC group exhibited improved DHI, decreased Pfirmann grading, and alleviated IDD. The structural integrity of the NP and annulus fibrosus increased, and the number of the NP increased. The levels of proteoglycan, COL Ⅱ, BCL-2 and GSK-3β increased, while the levels of MMP-3, MMP-9, MMP-13, P53, P21, P16, BAX, Cleaved Caspase-3, Wnt3a and β-catenin protein decreased. The mRNA expression of Wnt3a and β-catenin mRNA decreased, while GSK-3β mRNA expression increased (P<0.05). Compared with the low-dose QTC group, the high-dose QTC group showed further improvements in DHI, decrease in Pfirrmann grading (P<0.05), and greater alleviation of IDD. The structural integrity of NP and annulus fibrosus was further enhanced, and the number of NP cells further increased. The levels of proteoglycan, COL Ⅱ, BCL-2 and GSK-3β were higher, while the levels of MMP-3, MMP-9, MMP-13, P53, P21, P16, BAX, Cleaved Caspase-3, Wnt3a and β-catenin were lower. The mRNA expression of Wnt3a and β-catenin decreased, while GSK-3β mRNA expression increased (P<0.05). Compared with the high-dose QTC group, the high-dose QTC +agonist group showed a decrease of DHI, an increase of Pfirmann grading (P<0.05), significant aggravation of IDD, reduction in structural integrity of the NP and annulus fibrosus, a decrease of NP cell count, lower levels of proteoglycan, COL Ⅱ, BCL-2 and GSK-3β, and higher levels of MMP-3, MMP-9, MMP-13, P53, P21, P16, BAX and Cleaved Caspase-3. Additionally, GSK-3β mRNA expression decreased (P<0.05). ConclusionQTC can inhibit NP cell aging, apoptosis, and ECM degradation in IDD rats, and its therapeutic effect may be mediated through the inhibition of the Wnt/β-catenin pathway.
6.Effect and mechanism of compatibility of Astragali Radix-Puerariae Lobatae Radix on ferroptosis in T2DM insulin resistance rats
Shuang WEI ; Feng HAO ; Wenchun ZHANG ; Zhangyang ZHAO ; Ji LI ; Dongwei HAN ; Huan XING
China Pharmacy 2025;36(1):57-63
OBJECTIVE To explore the effect and potential mechanism of the compatibility of Astragali Radix-Puerariae Lobatae Radix on ferroptosis of liver cells in type 2 diabetes mellitus (T2DM) insulin resistance (IR) rats. METHODS Sixty male SD rats were randomly divided into control group (12 rats) and modeling group (48 rats). The modeling group was fed with a high- fat diet for 4 consecutive weeks and then given a one-time tail vein injection of 1% streptozotocin to establish T2DM IR model. The model rats were randomly divided into model group, the compatibility of Astragali Radix-Puerariae Lobatae Radix group [QG group, 4.05 g/(kg·d), intragastric administration], ferroptosis inhibitor ferrostatin-1 group [Fer-1 group, 5 mg/kg by intraperitoneal injection, once every other day], the compatibility of Astragali Radix-Puerariae Lobatae Radix+ferroptosis inducer erastin group [QG+erastin group, 4.05 g/(kg·d) by intragastric administration+erastin 10 mg/(kg·d), intraperitoneal injection]. After 4 weeks of intervention, serum fasting blood glucose (FBG) and fasting insulin (FINS) were measured in each group of rats, and homeostasis model assessment of insulin resistance (HOMA-IR) and the natural logarithm of insulin action index(IAI) were calculated; the serum levels of total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), aspartate transaminase (AST) and alanine transaminase (ALT), Fe2+ and Fe content, glutathione (GSH), malondialdehyde (MDA) and superoxide dismutase (SOD) levels, NADP+/NADPH ratio and reactive oxygen species (ROS) were determined. The pathological morphology of its liver tissue was observed; the protein expressions of glutathione peroxidase 4 (GPX4), ferritin heavy chain 1 (FTH1), long-chain acyl-CoA synthetase 3 (ACSL3), ACSL4, ferritin mitochondrial (FTMT), and cystine/glutamate anti-porter (xCT) in the liver tissue of rats were detected. RESULTS Compared with control group, the liver cells in the model group of rats showed disordered arrangement, swelling, deepened nuclear staining, and more infiltration of inflammatory cells, as well as a large number of hepatocyte vacuoles and steatosis; FBG (after medication), the levels of TC, TG, LDL-C, AST, ALT, FINS, MDA and ROS, HOMA-IR, Fe2+ and Fe content, NADP+/NADPH ratio and protein expression of ACSL4 were significantly increased or up-regulated, while the levels of HDL-C, GSH and SOD, IAI, protein expressions of GPX4, FTH1, ACSL3, FTMT and xCT were significantly reduced or down-regulated (P<0.01). Compared with the model group, both QG group and Fer-1 group showed varying degrees of improvement in pathological damage of liver tissue and the levels of the above indicators, the differences in the changes of most indicators were statistically significant (P<0.01 or P<0.05). Compared with QG group, the improvement of the above indexes of QG+erastin group had been reversed significantly (P<0.01). CONCLUSIONS The compatibility decoction of Astragali Radix-Puerariae Lobatae Radix can reduce the level of FBG in T2DM IR rats, and alleviate IR degree, ion overload and pathological damage of liver tissue. The above effects are related to the inhibition of ferroptosis.
7.Pharmacoeconomic evaluation of finerenone combined with standard treatment regimen in the treatment of diabetic nephropathy
Hai LIANG ; Runan XIA ; Panpan DI ; Mengmeng ZHAO ; Pengcheng ZHANG ; Yashen HOU ; Hong ZHANG ; Wei WU ; Miao YANG
China Pharmacy 2025;36(1):86-90
OBJECTIVE To evaluate the cost-effectiveness of finerenone combined with standard treatment regimen in the treatment of diabetic nephropathy (DN). METHODS From the perspective of healthcare service providers, a Markov model was established to simulate the dynamic changes of each stage in DN patients who received finerenone combined with the standard treatment regimen or the standard treatment regimen alone based on the phase Ⅲ clinical trial study of finerenone for DN. Markov model was used to perform the cost-effectiveness of long-term effects and the costs of the two therapies with a simulation cycle of 4 months, a simulation period of 15 years and an annual discount rate of 5%. At the same time, one-way sensitivity analysis and probability sensitivity analysis were performed, and the stability of the results was validated. RESULTS Accumulative cost of the standard treatment regimen was 579 329.54 yuan, and the accumulative utility was 8.052 4 quality-adjusted life year (QALYs); the accumulative cost of finerenone combined with the standard treatment regimen was 332 520.61 yuan, and the accumulative utility was 8.187 4 QALYs. Finerenone combined with the standard treatment regimen was more cost-effective. The results of one-way sensitivity analysis showed that dialysis status utility value, DN stage 3 utility value and DN stage 4 utility value had a great influence on the incremental cost-effectiveness ratio, but did not affect the robustness of the model. The results of probability sensitivity analysis showed that finerenone combined with the standard treatment regimen was more cost-effective with 100% probability. CONCLUSIONS For DN patients, finerenone combined with the standard treatment regimen is more cost-effective as an absolute advantage option.
8.Practice and reflection on ethical review of multicentre studies in a tertiary hospital
Lingling YU ; Wei LIU ; Pengjun ZHANG
Chinese Medical Ethics 2025;38(1):58-62
ObjectiveTo analyse the implementation of mutual recognition of ethical review in a tertiary hospital, providing ideas for exploring ethical review of multicenter studies. MethodsThe ethical review of multicenter studies conducted by the hospital from 2018 to 2022 was analyzed. ResultsA total of 1,582 projects were reviewed in the hospital from 2018 to 2022, of which 773 (48.9%) were multicentre studies. In multicenter study projects, 70.4% of the studies were conducted as a participating unit. Mutual recognition of ethical review and fast review were implemented for all participating projects. After a rapid review of 24 studies, the presiding committee recommended submitting them for conference review. The reasons for the transfer to conference review included issues with the study protocol (11 projects), informed consent (12 projects), and other supporting documents (5 projects). Twenty-one studies were eventually approved by the ethics committee after modification, and 3 studies were not approved by the ethics committee because the sponsor refused to modify the study protocols. ConclusionFor participating in multicentre studies, the ethics committees of participating units implement mutual recognition of ethical reviews and adopt a rapid review approach to review all study data, which can achieve both quality and efficiency.
9.Clinical Advantages and Key Research Points of Traditional Chinese Medicine in the Treatment of Atrial Fibrillation
Cong SUN ; Yujiang DONG ; Hongmei GAO ; Qing WEI ; Menghe ZHANG ; Xiaojing SHI ; Liya FENG
Journal of Traditional Chinese Medicine 2025;66(2):133-138
Traditional Chinese medicine (TCM) therapy has unique clinical advantages in the treatment of atrial fibrillation, mainly reflected in five aspects, improving quality of life, enabling early diagnosis and treatment, promoting cardiac rehabilitation, making up for the limitations of Western medicine, and improving the success rate of catheter ablation. However, there is insufficient evidence in current clinical research. Based on the current status of TCM research in the treatment of atrial fibrillation, it is suggested that future studies should focus on standardized research on syndrome differentiation and classification. This can be achieved through clinical epidemiological surveys, expert consensus, and other methods to establish a unified syndrome differentiation and classification standard for atrial fibrillation. Clinical efficacy evaluation indicators should be standardized, and core outcome measures for clinical research on TCM treatment of atrial fibrillation should be developed through systematic reviews, patient interviews, and other methods. Additionally, clinical research design, implementation, and data management should be improved. By leveraging modern information technologies such as artificial intelligence, the scientific and standardized nature of TCM intervention research on atrial fibrillation can be enhanced, ultimately improving the quality of research.
10.Establishment and analysis of chronic rejection model of mouse heart transplantation
Wei ZHANG ; Qingrong ZHANG ; Maolin MA ; Qianghua LENG ; Fei HAN
Organ Transplantation 2025;16(1):99-105
Objective To establish a chronic rejection (CR) model of mouse heart transplantation and analyze its characteristics. Methods Allogeneic BALB/c and C57BL/6 mice were used as donor and recipient for heart transplantation, and intraperitoneal injection of cytotoxic T lymphocyte-associated antigen 4-immunoglobulin (CTLA4-Ig) was given 1 and 2 days after surgery. Graft survival time, donor specific antibody (DSA) level, graft pathology and inflammatory cell infiltration were observed. Results In allogeneic transplantation model, graft survival time was prolonged after CTLA4-Ig treatment [(28.2±4.1) d vs. (7.0±0.7) d, P < 0.01]. The level of serum DSA-IgG increased at 2, 3 and 4 weeks after surgery, while the level of DSA-IgM remained unchanged. Myocardial cell injury, inflammatory cell infiltration, interstitial fibrosis and C4d deposition in capillaries were aggravated 3 weeks after operation and worsened 4 weeks after operation. The infiltrated immune cells were mainly macrophages, T cells and plasma cells. Conclusions Mouse allogeneic heart transplantation combined with CTLA4-Ig successfully establishes a CR model, which provides a basis for subsequent studies on the pathogenesis and intervention of CR.

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