1.Mechanism of Action of Kaixinsan in Ameliorating Alzheimer's Disease
Xiaoming HE ; Xiaotong WANG ; Dongyu MIN ; Xinxin WANG ; Meijia CHENG ; Yongming LIU ; Yetao JU ; Yali YANG ; Changbin YUAN ; Changyang YU ; Li ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(1):20-29
ObjectiveTo investigate the mechanism of action of Kaixinsan in the treatment of Alzheimer's disease (AD) based on network pharmacology, molecular docking, and animal experimental validation. MethodsThe Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP) and the Encyclopedia of Traditional Chinese Medicine(ETCM) databases were used to obtain the active ingredients and targets of Kaixinsan. GeneCards, Online Mendelian Inheritance in Man(OMIM), TTD, PharmGKB, and DrugBank databases were used to obtain the relevant targets of AD. The intersection (common targets) of the active ingredient targets of Kaixinsan and the relevant targets of AD was taken, and the network interaction analysis of the common targets was carried out in the STRING database to construct a protein-protein interaction(PPI) network. The CytoNCA plugin within Cytoscape was used to screen out the core targets, and the Metascape platform was used to perform gene ontology(GO) functional enrichment analysis and Kyoto encyclopedia of genes and genomes(KEGG) pathway enrichment analysis. The “drug-active ingredient-target” interaction network was constructed with the help of Cytoscape 3.8.2, and AutoDock Vina was used for molecular docking. Scopolamine (SCOP) was utilized for modeling and injected intraperitoneally once daily. Thirty-two male C57/BL6 mice were randomly divided into blank control (CON) group (0.9% NaCl, n=8), model (SCOP) group (3 mg·kg-1·d-1, n=8), positive control group (3 mg·kg-1·d-1 of SCOP+3 mg·kg-1·d-1 of Donepezil, n=8), and Kaixinsan group (3 mg·kg-1·d-1 of SCOP+6.5 g·kg-1·d-1 of Kaixinsan, n=8). Mice in each group were administered with 0.9% NaCl, Kaixinsan, or Donepezil by gavage twice a day for 14 days. Morris water maze experiment was used to observe the learning memory ability of mice. Hematoxylin-eosin (HE) staining method was used to observe the pathological changes in the CA1 area of the mouse hippocampus. Enzyme linked immunosorbent assay(ELISA) was used to determine the serum acetylcholine (ACh) and acetylcholinesterase (AChE) contents of mice. Western blot method was used to detect the protein expression levels of signal transducer and activator of transcription 3(STAT3) and nuclear transcription factor(NF)-κB p65 in the hippocampus of mice. ResultsA total of 73 active ingredients of Kaixinsan were obtained, and 578 potential targets (common targets) of Kaixinsan for the treatment of AD were screened out. Key active ingredients included kaempferol, gijugliflozin, etc.. Potential core targets were STAT3, NF-κB p65, et al. GO functional enrichment analysis obtained 3 124 biological functions, 254 cellular building blocks, and 461 molecular functions. KEGG pathway enrichment obtained 248 pathways, mainly involving cancer-related pathways, TRP pathway, cyclic adenosine monophosphate(cAMP) pathway, and NF-κB pathway. Molecular docking showed that the binding of the key active ingredients to the target targets was more stable. Morris water maze experiment indicated that Kaixinsan could improve the learning memory ability of SCOP-induced mice. HE staining and ELISA results showed that Kaixinsan had an ameliorating effect on central nerve injury in mice. Western blot test indicated that Kaixinsan had a down-regulating effect on the levels of NF-κB p65 phosphorylation and STAT3 phosphorylation in the hippocampal tissue of mice in the SCOP model. ConclusionKaixinsan can improve the cognitive impairment function in SCOP model mice and may reduce hippocampal neuronal damage and thus play a therapeutic role in the treatment of AD by regulating NF-κB p65, STAT3, and other targets involved in the NF-κB signaling pathway.
2.Therapeutic Effect and Mechanism of Shentong Zhuyutang Combined with Dilongtang in Treatment of Lumbar Disc Herniation with Qi Stagnation and Blood Stasis Syndrome
Huangsheng TAN ; Yinbo WANG ; Yong HUANG ; Juyi LAI ; Hualong FENG ; Zhiming LAN ; Yuanfei FU ; Yong JIANG ; Shenghua HE
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(1):47-54
ObjectiveTo observe the clinical efficacy of Shentong Zhuyutang combined with Dilongtang in the treatment of lumbar disc herniation (LDH) with Qi stagnation and blood stasis syndrome, and its effect on nucleus pulposus reabsorption and immune-inflammatory factors, exploring its therapeutic mechanism from the perspective of reabsorption. MethodsA total of 120 patients with LDH from the Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, treated between June 2020 and January 2023, were randomly divided into the control group (52 cases, with 8 dropouts) and the observation group (49 cases, with 11 dropouts) according to a random number table. The control group received routine treatment, while the observation group was treated with Shentong Zhuyutang combined with Dilongtang in addition to routine treatment. Visual Analogue Scale (VAS), Oswestry Disability Index (ODI), Japanese Orthopaedic Association (JOA) score, and traditional Chinese medicine (TCM) syndrome score were measured before treatment and after 3 courses of treatment. Venous blood samples were collected for the determination of serological indexes. MR examination was performed during the 6-month follow-up to calculate the absorption rate. ResultsAfter treatment, both groups showed significant reductions in VAS, ODI, TCM syndrome score, serum tumor necrosis factor (TNF)-α, matrix metalloproteinase (MMP)-9, and vascular endothelial growth factor (VEGF) levels, and a significant increase in JOA score compared with pre-treatment values (P<0.05). Compared with the control group, the observation group showed significantly lower VAS, ODI, TCM syndrome score, serum TNF-α, MMP-9, and VEGF levels, and a significantly higher JOA score (P<0.05). The proportion of nucleus pulposus reabsorption in the observation group was 57.14% (28/49), significantly higher than 21.15% (11/52) in the control group (χ2=6.161, P<0.05). ConclusionShentong Zhuyutang combined with Dilongtang can effectively relieve pain, improve lumbar function, and alleviate TCM clinical symptoms in LDH patients with Qi stagnation and blood stasis syndrome. Imaging findings suggest that the treatment promotes the reabsorption of nucleus pulposus protrusion, while laboratory testing shows reduced serum levels of TNF-α, MMP-9, and VEGF, which contribute to the rehabilitation of patients.
3.Da Chaihutang for Treatment of Sepsis with Yang Syndrome:A Randomized Controlled Trial
Na HUANG ; Guangmei CHEN ; Xingyu KAO ; Zhen YANG ; Weixian XU ; Kang YUAN ; Junna LEI ; Jingli CHEN ; Mingfeng HE
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(1):55-63
ObjectiveTo explore the clinical efficacy and safety of Da Chaihutang (DCH) for the treatment of sepsis with Yang syndrome. MethodsA total of 70 patients suffering from sepsis with Yang syndrome were randomly divided into an observation group and a control group, with 35 cases in each group. They both received standard Western medicine treatment. The observation group was additionally given a dose of DCH, which was boiled into 100 mL and taken twice. The control group was additionally given an equal volume and dosage of warm water. The intervention lasted for three days. The 28-day all-cause mortality and the changes in the following indicators before and after intervention were compared between the two groups, including sequential organ failure assessment (SOFA), acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) score,white blood cell (WBC),the percentage of neutrophils (NEU%),C-reactive protein (CRP),procalcitonin (PCT),alanine transaminase (ALT),aspartate transaminase (AST),total bilirubin (TBil),creatinine (Cr),blood urea nitrogen (BUN),acute gastrointestinal injury (AGI) grade,gastrointestinal dysfunction score (GDS),serum intestinal fatty acid-binding protein (iFABP), citrulline (CR),platelet (PLT),prothrombin time(PT),activated partial thromboplastin time (APTT),fibrinogen (Fib),international normalized ratio (INR),and D-dimer (D-D). ResultsThere was no significant difference between the two groups regarding 28-day all-cause mortality. After the intervention,SOFA,WBC,PCT,and Cr were significantly decreased, and PLT was significantly increased in the control group (P<0.05). SOFA,APACHE Ⅱ,NEU%,CRP,PCT,ALT,AST,Cr,BUN,AGI grade,GDS,and serum iFABP and CR were significantly improved in the observation group (P<0.05). After the intervention,APACHE Ⅱ,PCT,AGI grade,GDS,and serum iFABP in the observation group were significantly lower than those in the control group ,while CR and PLT were higher (P<0.05,P<0.01). There were significant differences regarding the gap of SOFA,APACHE Ⅱ,AST,TBil,AGI grade,GDS,iFABP,CR, and PLT between the two groups (P<0.05,P<0.01). There were slight differences regarding PT,APTT,Fib,INR,and D-D between the two groups,which were in the clinical normal range. ConclusionOn the basis of Western medicine, DCH helped to reduce sepsis severity and improved multiple organ dysfunction with high clinical efficacy and safety, but further research on its impact on the prognosis of patients with sepsis is still required.
4.Accuracy comparison of different calculation formulas for intraocular lens degree in cataract patients with short axial length under different biometric parameters
Yang XIA ; Yunxia LIN ; Ling XU
International Eye Science 2025;25(1):112-117
AIM: To compare the refractive prediction accuracy of 7 intraocular lens(IOL)calculation formulas in the cataract eyes with short axial length(AL)at different corneal curvatures and anterior chamber depth(ACD), and analyze relevant influencing factors contributing to prediction errors.METHODS: A retrospective analysis was performed for 125 patients(125 eyes)with a short AL, who received cataract phacoemulsification at Shenyang He Eye Specialist Hospital from November 2020 to December 2021. According to the keratometry(Km), they were divided into low flat Km group(≤45.5 D), medium and high Km group(45.5 D
5.Correlation of serum leucine-rich α-2 glycoprotein 1 and fibroblast growth factor 21 levels with neovascular glaucoma
Zhong LUO ; He ZHOU ; Yi HUANG ; Wanjiang DONG
International Eye Science 2025;25(1):118-121
AIM: To investigate the correlation of serum leucine-rich α-2 glycoprotein 1(LRG1)and fibroblast growth factor 21(FGF-21)levels with neovascular glaucoma(NVG).METHODS: A total of 110 cases(110 eyes)with NVG admitted to the ophthalmology department from September 2020 to September 2022 were selected as NVG group, with 23 cases of grade II, 44 cases of grade III, and 43 cases of grade IV, while 90 sex and age matched cataract patients(90 eyes)were selected as control group. The levels of LRG1, FGF-21, vascular endothelial growth factor(VEGF), pigment epithelium-derived factor(PEDF), and tumor necrosis factor-α(TNF-α)in serum were detected by ELISA; Pearson correlation analysis was used to analyze the correlation of serum LRG1 and FGF-21 levels with Teich grade, VEGF, PEDF and TNF-α levels.RESULTS: The levels of serum LRG1, FGF-21, VEGF, PEDF and TNF-α in the NVG group were significantly higher than those in the control group(all P<0.01). With the increase of Teich grading, the levels of serum LRG1, FGF-21, VEGF, PEDF and TNF-α in NVG patients significantly increased in turn(all P<0.05). Correlation analysis showed that the levels of LRG1 and FGF-21 in serum of NVG patients were positively correlated with the levels of VEGF, PEDF and TNF-α(all P<0.05).CONCLUSION: The levels of LRG1 and FGF-21 in serum of patients with NVG are obviously increased, which are positively correlated with the levels of VEGF, PEDF and TNF-α, both of which may be related to the development of NVG.
6.Qingre Sanzhuo Decoction Treats Gouty Arthritis Combined with Hyperuricaemia in Rats via NLRP3/ASC/Caspase-1 Pathway
Haolin LI ; Qian BAI ; Weigang CHENG ; Weiqing LI ; Juanjuan YANG ; Peixin HE ; Huijun YANG ; Haidong WANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(3):49-57
ObjectiveTo investigate the effect and mechanism of Qingre Sanzhuo decoction in treating gouty arthritis (GA) combined with hyperuricaemia (HUA). MethodsSixty male SD rats were randomized into normal, model, colchicine (0.5 mg·kg-1), and low-, medium-, and high-dose (17, 34, 68 g·kg-1, respectively) Qingre Sanzhuo decoction groups (n=10). The rats in other groups except the normal group were treated with the modified method for the modeling of GA combined with HUA. The drug intervention groups were administrated with corresponding drugs by gavage in the afternoon every day and the normal group and the model group were administrated with an equal volume of sterile normal saline by gavage. The level of uric acid (SUA) in the serum was measured 2 h after the last administration. The degree of ankle joint swelling was calculated 0.5, 12, 24, 48 h after modeling, and joint inflammation was scored. The pathological changes of ankle joints were observed by hematoxylin-eosin staining, and the serum levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), C reactive protein (CRP), and interleukin-18 (IL-18) were measured by enzyme-linked immunosorbent assay. Real-time PCR was performed to determine the mRNA levels of NOD-like receptor protein 3 (NLRP3), apoptosis-associated speck-like protein containing CARD (ASC), cysteinyl aspartate-specific protease-1 (Caspase-1), gasdermin D (GSDMD), and nuclear factor-kappa B (NF-κB) in the synovial tissue of ankle joints. Western blot was employed to determine the protein levels of NLRP3, ASC, and Caspase-1 in ankle joints. The immunohistochemical method was used to detect the expression of GSDMD and NF-κB in the synovial tissue of ankle joints. ResultsCompared with the normal group, the model group showed increased SUA in the serum (P<0.05), ankle joint swelling and joint inflammation (P<0.05), increased number of blood vessels in the synovium, inflammatory cell foci in the synovial bursa, elevated serum levels of TNF-α, IL-1β, CRP, and IL-18 (P<0.05), and up-regulated mRNA and protein levels of NLRP3, ASC, Caspase-1, GSDMD, and NF-κB in the synovial tissue of ankle joints (P<0.05). Compared with the model group, the medium- and high-dose Qingre Sanzhuo decoction groups showed reduced SUA in the serum (P<0.05), alleviated ankle joint swelling and joint inflammation (P<0.05), lowered serum levels of TNF-α, IL-1β, CRP, and IL-18 (P<0.05), and down-regulated mRNA and protein levels of NLRP3, ASC, Caspase-1, GSDMD, and NF-κB in the synovial tissue of ankle joints (P<0.05). However, in terms of ameliorating the pathological changes of ankle joints, only the high-dose Qingre Sanzhuo decoction group showed normal morphology of the synovial membrane of ankle joints and no obvious lesion in the articular cartilage. ConclusionQingre Sanzhuo decoction may play a role in preventing and controlling GA combined with HUA by down-regulating the activity of NLRP3/ASC/Caspase-1 pathway and inhibiting the expression of inflammatory cytokines, such as TNF-α, IL-1β, CRP, and IL-18.
7.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.
8.Formation and Theoretical Explanation of the Exterior-Interior Relationships among Channels in The Inner Canon of Yellow Emperor (《黄帝内经》)
Journal of Traditional Chinese Medicine 2025;66(1):6-11
Regarding the pathway and distribution of twelve channels, the current general view emphasizes their longitudinal distribution along the surface of the human body. Based on such a positioning, it is difficult to interpret the three yin and three yang "opening-closing- pivoting" theory, and the theory of the six channels transmission of externally-contracted febrile disease. Through combing the relevant contents in The Inner Canon of Yellow Emperor (《黄帝内经》), it is proposed that, in addition to the longitudinal regional distribution of the channels on the human body, they also exhibit characteristics of layered distribution between the exterior and interior. The formation of this theory stems from the combination of body tissue and channels, that is, the taiyang governs the function of skin, yangming governs the function of flesh, and shaoyang governs the function of bone; taiyin governs the function of spleen and stomach, jueyin governs the function of liver, and shaoyin governs the function of heart. The process of integration of the channels with the body tissues has a relatively clear imprint in the syndrome differentiation of febrile disease in The Inner Canon of Yellow Emperor. The exterior-interior relationships of channels are the foundation and prerequisite for the theory of the three yin and three yang "opening-closing-pivoting" and the theory of the six channels transmission in Plain Questions·Treatise on Heat (《素问·热论篇》).
9.Cognition and countermeasures of medical science and technology ethics management among medical staff in five tertiary hospitals in Ningxia Hui Autonomous Region
Chinese Medical Ethics 2025;38(1):63-71
ObjectiveTo understand the current situation and influencing factors of cognition level, as well as existing problems in the construction of medical science and technology ethics management among medical staff in five tertiary hospitals in Ningxia Hui Autonomous Region, to provide references for enhancing their awareness of medical science and technology ethics management and improving the quality of clinical research. MethodsUsing a self-designed and validated “Medical Science and Technology Ethics Management Cognitive Questionnaire for Medical Staff,” medical staff from five tertiary hospitals in five cities in Ningxia were selected as the research subjects for investigation. ResultsFinally, 436 valid questionnaires were collected, among which the total average score for medical staff’s cognition of medical science and technology ethics management was (61.58±12.96) points. The scores of ethics system cognition, ethics committee cognition, ethics education and training cognition, and ethics management informatization cognition were (14.18±2.84) points, (24.19±5.47) points, (15.07±4.00) points, and (8.14±4.42) points, respectively. Multiple linear regression analysis showed that age, work city, education level, professional title, whether they had assessed the implementation of the hospital ethics system, whether they had participated in the hospital’s ethics review work, and whether they had organized or participated the hospital’s ethics training, were all influencing factors on the cognitive score of medical science and technology ethics management among medical staff, which can explain 51.00% of the variation (P<0.05). Medical staff considered that inadequate promotion of ethical systems, opaque ethical review procedures and processes, conflicts between ethical training time and work tasks, and the lack of a dedicated ethical review information platform were the main problems in constructing medical science and technology ethics. ConclusionThe cognition level of medical science and technology ethics management among medical staff in tertiary hospitals in Ningxia was generally not high and was influenced by various factors. Hospital managers should strengthen the publicity and training of ethical systems, as well as improve their implementation and supervision mechanisms; standardize ethical review procedures and processes, as well as build an ethical review information platform; increase investment in ethics education and arrange training time reasonably, to enhance the awareness of medical science and technology ethics management among medical staff and improve the quality of clinical research.
10.A prediction model for high-risk cardiovascular disease among residents aged 35 to 75 years
ZHOU Guoying ; XING Lili ; SU Ying ; LIU Hongjie ; LIU He ; WANG Di ; XUE Jinfeng ; DAI Wei ; WANG Jing ; YANG Xinghua
Journal of Preventive Medicine 2025;37(1):12-16
Objective:
To establish a prediction model for high-risk cardiovascular disease (CVD) among residents aged 35 to 75 years, so as to provide the basis for improving CVD prevention and control measures.
Methods:
Permanent residents aged 35 to 75 years were selected from Dongcheng District, Beijing Municipality using the stratified random sampling method from 2018 to 2023. Demographic information, lifestyle, waist circumference and blood biochemical indicators were collected through questionnaire surveys, physical examinations and laboratory tests. Influencing factors for high-risk CVD among residents aged 35 to 75 years were identified using a multivariable logistic regression model, and a prediction model for high-risk CVD was established. The predictive effect was evaluated using the receiver operating characteristic (ROC) curve.
Results:
A total of 6 968 individuals were surveyed, including 2 821 males (40.49%) and 4 147 females (59.51%), and had a mean age of (59.92±9.33) years. There were 1 155 high-risk CVD population, with a detection rate of 16.58%. Multivariable logistic regression analysis showed that gender, age, smoking, central obesity, systolic blood pressure, fasting blood glucose, triglyceride and low-density lipoprotein cholesterol were influencing factors for high-risk CVD among residents aged 35 to 75 years (all P<0.05). The area under the ROC curve of the established prediction model was 0.849 (95%CI: 0.834-0.863), with a sensitivity of 0.693 and a specificity of 0.863, indicating good discrimination.
Conclusion
The model constructed by eight factors including demographic characteristics, lifestyle and blood biochemical indicators has good predictive value for high-risk CVD among residents aged 35 to 75 years.


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