1.Traditional Chinese Medicine Treats Esophageal Cancer via PI3K/Akt Signaling Pathway: A Review
Wei GUO ; Chen PENG ; Yikun WANG ; Zixuan YU ; Jintao LIU ; Jing DING ; Yijing LI ; Hongxin SUN
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(5):302-311
Esophageal cancer (EC) is a highly prevalent malignant tumor in China. The phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway, as one of the key oncogenic pathways, can promote the cell cycle progression, proliferation, migration, and invasion, induce chemoresistance, and inhibit apoptosis and autophagy of EC cells. Traditional Chinese medicine (TCM), with the advantages of targeting multiple points with multiple components to delay cancer progression, can target the PI3K/Akt signaling pathway for EC treatment. This article preliminarily discusses the molecular mechanism and role of the PI3K/Akt signaling pathway in EC and elaborates on the specific targets and efficacy of TCM in treating EC through intervention in the PI3K/Akt signaling pathway in the past five years. TCM materials and extracts inhibiting the PI3K/Akt signaling pathway in EC include Borneolum, spore powder of Ganoderma lucidum without spore coat, extract of Celastrus orbiculatus, root extract of Taraxacum, and Bruceae Fructus oil emulsion. TCM active ingredients exerting the effect include flavonoids, terpenoids, saponins, phenols, polysaccharides, alkaloids, and other compounds. TCM compound prescriptions with such effect include Qige San, Huqi San, Xuanfu Daizhetang, Tongyoutang and its decomposed prescriptions, Liujunzi Tang, and Xishenzhi Formula. In addition, TCM injections such as Compound Kushen Injection and Kang'ai injection also inhibit the PI3K/Akt signaling pathway in EC. This paper summarizes the role of the PI3K/Akt signaling pathway in EC and the TCM interventions, aiming to provide reference for the research and clinical application of new drugs for EC.
2.Mechanism of Danggui Shaoyaosan in Improving Glomerulosclerosis in db/db Mice via SIRT1/HIF-1α/VLDLr Signaling Pathway
Ruijia LI ; Zixuan WANG ; Shilong GUO ; Jing LI ; Qianqian ZHANG ; Wen DONG ; Dengzhou GUO
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(6):11-18
ObjectiveTo investigate the potential mechanism of Danggui Shaoyaosan (DSS) in ameliorating renal injury in db/db mice. MethodsThirty 8-week-old specific pathogen-free (SPF)-grade male db/db mice and six db/m mice were acclimated for one week. Urinary microalbumin and blood glucose levels were measured weekly in both db/db and db/m mice. Successful modeling was determined by significantly higher microalbuminuria in db/db mice compared to db/m mice and a fasting blood glucose ≥16.7 mmol·L-1. The 30 db/db mice were randomly divided into five groups: the model group, the irbesartan (IBN) group, and three DSS dose groups (low-, medium-, and high-dose DSS groups, administered at 16.77, 33.54, 67.08 g·kg-1·d-1, respectively). Additionally, the six db/m mice served as the normal control group. The IBN group received irbesartan at 0.025 g·kg-1·d-1 by gavage, while the three DSS groups received DSS at 16.77, 33.54, and 67.08 g·kg-1·d-1 by gavage, respectively. The normal and model groups were administered with an equivalent volume of normal saline by gavage. All interventions lasted for 8 consecutive weeks. After intervention, serum creatinine (SCr), blood urea nitrogen (BUN), urinary total protein (UTP), triglyceride (TG), and low-density lipoprotein cholesterol (LDL-C) were measured to evaluate the therapeutic efficacy of the treatments. Renal histopathological changes were observed with hematoxylin-eosin (HE) staining. Western blot was used to detect the protein expression of silencing information regulator 1 (SIRT1), hypoxia-inducible factor-1α (HIF-1α), very low-density lipoprotein receptor (VLDLr), and cluster of differentiation 31 (CD31). Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) was used to detect the mRNA levels of HIF-1α and VLDLr. Immunohistochemistry was used to observe the expression and distribution of HIF-1α and Caspase-3. ResultsCompared to the normal group, the model group showed significantly increased SCr, BUN, UTP, TG, and LDL-C. HE staining revealed glomerulosclerosis, mesangial matrix hyperplasia, capillary loop distortion and thickening, with extensive inflammatory cell infiltration. Protein expression of SIRT1 and CD31 significantly decreased (P<0.05), while HIF-1α and VLDLr protein and mRNA levels increased (P<0.05). Immunohistochemistry showed increased expression of HIF-1α and Caspase-3 (P<0.05), indicating hypoxia and apoptosis in renal cells. In all treatment groups, SCr, BUN, TG, and LDL-C were significantly reduced compared to the model group (P<0.05), and UTP was significantly improved in the medium-dose DSS group (P<0.05). Renal tissue structure and morphology were improved, inflammatory cells were reduced, and no vascular hyaline degeneration was observed. SIRT1 and CD31 protein expression was elevated to varying degrees compared to the model group (P<0.05), while HIF-1α and VLDLr protein and mRNA levels decreased (P<0.05). Immunohistochemistry showed reduced expression of HIF-1α and Caspase-3 in all treatment groups (P<0.05), with the most significant improvement observed in the IBN group and medium-dose DSS group (P<0.05). ConclusionDSS can effectively ameliorate glomerulosclerosis and lipid deposition in db/db mice, and its mechanism may involve the SIRT1/HIF-1α/VLDLr signaling pathway.
3.Mechanism of Danggui Shaoyaosan in Improving Inflammatory Response in Mice with Diabetic Kidney Disease Based on TLR4/p65/NLRP3 Signaling Pathway
Shilong GUO ; Ruijia LI ; Zixuan WANG ; Xinai WANG ; Luyu HOU ; Wenjing SHI ; Mengyuan TIAN ; Dengzhou GUO
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(6):19-27
ObjectiveTo investigate the effect of Danggui Shaoyaosan on the expression of Toll-like receptor 4/nuclear factor-kappa B p65/NOD-like receptor protein 3 (TLR4/NF-κB p65/NLRP3) signaling pathway in the renal tissues of db/db mice with spontaneous diabetes, and to explore the potential mechanism by which Danggui Shaoyaosan alleviates inflammation in diabetic kidney disease (DKD). MethodsThirty db/db mice were divided into five groups: A model group, Danggui Shaoyaosan low- (16.77 g·kg-1·d-1), medium- (33.54 g·kg-1·d-1), and high-dose (67.08 g·kg-1·d-1) intervention groups, as well as an irbesartan group (0.025 g·kg-1·d-1) by the random number table method, with 6 mice in each group. Additionally, 6 db/m mice were assigned to the normal group. After 8 weeks of intervention, the following parameters were determined by corresponding methods: body weight, fasting blood glucose (FBG), 24-hour urinary protein (24 h-UTP), and serum creatinine (SCr) levels, renal histopathological analysis by hematoxylin-eosin (HE) staining, Masson staining, and periodic acid-Schiff (PAS) staining, the protein and mRNA expression levels of TLR4, NF-κB p65, NLRP3, tumor necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-10 (IL-10), and interleukin-18 (IL-18) by Western blot and Real-time quantitative polymerase chain reaction (Real-time PCR), as well as TLR4, NF-κB p65, and NLRP3 protein expression in renal tissues by immunohistochemistry (IHC). ResultsCompared with the normal group, the model group exhibited increased body weight, FBG, 24 h-UTP, and SCr levels (P<0.05); disordered renal structure, thickened basement membrane, and interstitial inflammatory cell infiltration, elevated TLR4, NF-κB p65, NLRP3, TNF-α, IL-1β, IL-6, and IL-18 expression; as well as decreased IL-10 expression (P<0.05). Compared with the model group, these pathological changes and biochemical abnormalities were reversed in the medicine intervention groups to varying degrees (P<0.05). ConclusionDanggui Shaoyaosan may delay DKD progression by alleviating renal inflammatory response and reducing urinary protein excretion via modulating the TLR4/NF-κB p65/NLRP3 signaling pathway.
4.Protective Effect and Potential Mechanism of Danggui Shaoyaosan on Diabetic Kidney Disease in db/db Mice Based on Endoplasmic Reticulum Stress in Glomerular Endothelial Cells
Ruijia LI ; Zixuan WANG ; Shilong GUO ; Sen YANG ; Jing LI ; Qianqian ZHANG ; Wen DONG ; Dengzhou GUO
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(6):28-35
ObjectiveTo investigate the therapeutic efficacy of Danggui Shaoyaosan (DSS) on renal injury in db/db mice and its impact on endoplasmic reticulum stress (ERS) in renal tissues. MethodsThirty 8-week-old male db/db mice and six db/m mice were acclimated for one week, after which urinary microalbumin and blood glucose levels were monitored to establish a diabetic kidney disease (DKD) model. The model mice were randomly divided into a model group, an irbesartan group, and three DSS treatment groups with different doses (16.77, 33.54, and 67.08 g·kg-1·d-1). A normal group was set as control. Each group was intragastrically administered with the corresponding drugs or saline for 8 weeks. After the intervention, general conditions were observed. Serum cystatin C (Cys-C), 24-hour urinary total protein (24 h-UTP), 24-hour urinary microalbumin (24 h-UMA), urinary creatinine (Ucr), and urea nitrogen (UUN) were measured. Transmission electron microscopy (TEM) was used to observe glomerular basement membrane (GBM) and ultrastructural changes of the endoplasmic reticulum (ER) in glomerular endothelial cells. Western blot, real-time fluorescence quantitative polymerase chain reaction (Real-time PCR), and immunohistochemistry were used to analyze renal tissue structure and the expression of GRP78, CHOP, and related markers. ResultsCompared with the normal group, the mice in the model group showed curled posture, sluggish response, poor fur condition, increased levels of Cys-C, 24 h-UTP, 24 h-UMA, and UUN (P<0.05), while Ucr decreased (P<0.05). The GBM was significantly thickened, with podocyte and foot process fusion. The protein expressions of GRP78, CHOP, and ATF6 were significantly upregulated (P<0.05), the mRNA levels of GRP78 and CHOP increased (P<0.05), and immunohistochemistry showed an enhanced GRP78 signal (P<0.05). After treatment, the mice exhibited improved behavior, normalized GBM and podocyte structure, improved ER morphology and markedly better biochemical indicators. Western blot, Real-time PCR, and immunohistochemistry indicated that the ERS-related markers were downregulated in the DSS treatment groups (P<0.05), suggesting alleviated ERS and improved renal function. ConclusionDSS can effectively ameliorate renal pathological damage in db/db mice, possibly by regulating ERS in glomerular endothelial cells, although the underlying signaling mechanisms require further investigation.
5.Alpha-ketoglutarate engineered small extracellular vesicles delay skin aging
Zhijing WU ; Jiali LI ; Jiaxin ZHANG ; Tangrong WANG ; Yuzhou ZHENG ; Zixuan SUN
Chinese Journal of Tissue Engineering Research 2026;30(1):120-129
BACKGROUND:Cell-free therapy is a research hotspot in the field of medical cosmetic anti-aging.It is still unknown for paracellular secretion of human umbilical cord mesenchymal stem cell-derived small extracellular vesicles loaded with the antiaging drug α-ketoglutaric acid to delay skin aging.OBJECTIVE:To investigate the effect of the anti-aging agent α-ketoglutarate engineered human umbilical cord mesenchymal stem cell-derived small extracellular vesicles in a D-galactose-induced model of dermal fibroblast senescence.METHODS:(1)Biological characteristics of primary human umbilical cord mesenchymal stem cells were identified by osteogenic-lipogenic differentiation staining and flow cytometry.(2)The small extracellular vesicles derived from human umbilical cord mesenchymal stem cell were obtained by using differential-ultracentrifugation.α-Ketoglutarate-engineered human umbilical cord mesenchymal stem cell-small extracellular vesicles were constructed by electroporation,and biologically characterized by transmission electron microscopy and nanoparticle tracking analyzer,while the encapsulation rate was assessed using high-performance liquid chromatography.(3)The effect of α-ketoglutarate on the proliferative capacity of dermal fibroblasts was assessed by CCK-8 and Edu cell proliferation assay kits.(4)The effect of α-ketoglutarate-engineered human umbilical cord mesenchymal stem cell-small extracellular vesicles on delaying the senescence of dermal fibroblasts was evaluated by reactive oxygen species detection kit,western blot assay,and cellular immunofluorescence.RESULTS AND CONCLUSION:(1)The obtained human umbilical cord mesenchymal stem cell and human umbilical cord mesenchymal stem cell-small extracellular vesicles were biologically compatible.(2)There was no toxic effect on dermal fibroblasts when α-ketoglutarate was used in the concentration range of 0.5-8 mmol/L.(3)D-gal induced senescence in dermal fibroblasts,while α-ketoglutarate-engineered human umbilical cord mesenchymal stem cell-small extracellular vesicles treatment reduced the level of oxidative stress,DNA damage,and collagen loss,which was further verified that α-ketoglutarate-engineered human umbilical cord mesenchymal stem cell-small extracellular vesicles could effectively slow down the skin aging process.
6.Alpha-ketoglutarate engineered small extracellular vesicles delay skin aging
Zhijing WU ; Jiali LI ; Jiaxin ZHANG ; Tangrong WANG ; Yuzhou ZHENG ; Zixuan SUN
Chinese Journal of Tissue Engineering Research 2026;30(1):120-129
BACKGROUND:Cell-free therapy is a research hotspot in the field of medical cosmetic anti-aging.It is still unknown for paracellular secretion of human umbilical cord mesenchymal stem cell-derived small extracellular vesicles loaded with the antiaging drug α-ketoglutaric acid to delay skin aging.OBJECTIVE:To investigate the effect of the anti-aging agent α-ketoglutarate engineered human umbilical cord mesenchymal stem cell-derived small extracellular vesicles in a D-galactose-induced model of dermal fibroblast senescence.METHODS:(1)Biological characteristics of primary human umbilical cord mesenchymal stem cells were identified by osteogenic-lipogenic differentiation staining and flow cytometry.(2)The small extracellular vesicles derived from human umbilical cord mesenchymal stem cell were obtained by using differential-ultracentrifugation.α-Ketoglutarate-engineered human umbilical cord mesenchymal stem cell-small extracellular vesicles were constructed by electroporation,and biologically characterized by transmission electron microscopy and nanoparticle tracking analyzer,while the encapsulation rate was assessed using high-performance liquid chromatography.(3)The effect of α-ketoglutarate on the proliferative capacity of dermal fibroblasts was assessed by CCK-8 and Edu cell proliferation assay kits.(4)The effect of α-ketoglutarate-engineered human umbilical cord mesenchymal stem cell-small extracellular vesicles on delaying the senescence of dermal fibroblasts was evaluated by reactive oxygen species detection kit,western blot assay,and cellular immunofluorescence.RESULTS AND CONCLUSION:(1)The obtained human umbilical cord mesenchymal stem cell and human umbilical cord mesenchymal stem cell-small extracellular vesicles were biologically compatible.(2)There was no toxic effect on dermal fibroblasts when α-ketoglutarate was used in the concentration range of 0.5-8 mmol/L.(3)D-gal induced senescence in dermal fibroblasts,while α-ketoglutarate-engineered human umbilical cord mesenchymal stem cell-small extracellular vesicles treatment reduced the level of oxidative stress,DNA damage,and collagen loss,which was further verified that α-ketoglutarate-engineered human umbilical cord mesenchymal stem cell-small extracellular vesicles could effectively slow down the skin aging process.
7.Progress on active components and mechanisms of Traditional Chinese Medicine in the prevention and treatment of acute lung injury
Zixuan ZHANG ; Yuan GAO ; Li ZHANG ; Jiali LI ; Xike XU ; Xianpeng ZU
Journal of Pharmaceutical Practice and Service 2025;43(9):421-426
Acute lung injury (ALI) refers to the rapid onset of dyspnea, hypoxemia, and diffuse alveolar damage induced by various direct and indirect injurious factors, representing one of the clinically common diseases with a high mortality rate. However, there is currently a lack of specific therapeutic interventions targeting their underlying pathological mechanisms. Western medical treatment primarily relies on supportive care, and the existing pharmacological agents for ALI are predominantly corticosteroids, which, while efficacious, often accompany severe adverse effects. Recent research has revealed that numerous active components in Traditional Chinese Medicine (TCM) exhibit remarkable efficacy in the prevention and treatment of ALI, providing new insights into the therapeutic approaches for ALI. In this article, the pathological mechanisms of ALI and the roles and mechanisms of active components from TCM in the prevention and treatment of ALI were reviewed, aiming to provide a theoretical basis for the development of new drugs for the prevention and treatment of ALI.
8.Application of progressive exercise training based on mMRC grading in respiratory rehabilitation for patients with chronic obstructive pulmonary disease in a primary healthcare setting
Tingting GE ; Chengyue ZHU ; Yanan ZHANG ; Zixuan ZHENG ; Jiannan LI ; Junqing LI ; Zhijun JIE ; Jindong SHI ; Hanwei ZHAO
Chinese Journal of Clinical Medicine 2025;32(4):578-584
Objective To explore the efficacy of progressive exercise training based on the modified Medical Research Council dyspnea scale (mMRC) grading in respiratory rehabilitation for patients with chronic obstructive pulmonary disease (COPD) at a primary healthcare setting. Methods A total of 106 patients with COPD admitted to Zhuanqiao Community Health Service Center in Shanghai from Aug.1, 2022 to Jul. 30, 2024 were selected as research subjects. They were randomly divided into a study group and a control group in a 1∶1 ratio, with 53 patients in each group. The control group received conventional treatment, while the study group received conventional treatment combined with progressive exercise training. After 4 weeks of continuous treatment, the changes in the 6-minute walk test (6MWT), COPD assessment test (CAT) score, mMRC grading, Global Initiative for Chronic Obstructive Lung Disease (GOLD) grading and pulmonary function were compared between the two groups. Results Patients in both groups showed improvements in 6MWT distance, CAT score, mMRC grading, GOLD grading, and pulmonary function compared to baseline (P<0.05). Moreover, the study group had better improvements in 6MWT distance, CAT score, mMRC grading, GOLD grading, and pulmonary function than the control group (P<0.05). Conclusions Conventional treatment combined with progressive exercise training based on mMRC grading can enhance the effect of respiratory rehabilitation in patients with COPD, particularly in improving pulmonary function and exercise tolerance.
9.Research on the mediating effect of clinicians’ empathy ability between medical narrative competence and humanistic care quality
Ziqi LI ; Jiawen LIU ; Zixuan LI ; Yun LIU
Chinese Medical Ethics 2025;38(10):1365-1372
ObjectiveTo explore the mediating effect of empathy ability on clinicians’ medical narrative competence and humanistic care quality, and to provide data support for the improvement of clinicians’ empathy ability, narrative competence, and humanistic care quality. MethodsEmploying a convenience sampling method, a questionnaire survey was conducted among clinicians in Hebei province using a general data questionnaire, the Chinese Physician Narrative Behavior Scale, the Chinese version of the Jefferson Scale of Empathy, and the Humanistic Care Quality Scale. SPSS 21.0 software was used to analyze the current situation and correlation of clinicians’ medical narrative competence, empathy ability, and humanistic care quality. Amos 26.0 software was utilized to construct the structural equation model, and the Bootstrap method was adopted to test this model. ResultsThe scores of clinicians’ medical narrative competence, empathy ability, and humanistic care quality were (84.436±11.939), (106.058±18.936), and (117.652±14.087), respectively. There were significantly positive correlations between clinicians’ medical narrative competence and humanistic care quality (r = 0.530, P<0.01), between empathy ability and humanistic care quality (r=0.416, P < 0.01), as well as between medical narrative competence and empathy ability (r=0.176, P<0.01). Clinicians’ medical narrative competence had a positive predictive effect on humanistic care quality (β = 0.649, P < 0.001). The empathy ability of clinicians played a partial mediating role between medical narrative competence and humanistic care quality (β = 0.061, P < 0.001), with a mediating effect size of 0.068, accounting for 8.59% of the total effect. ConclusionClinicians’ medical narrative ability, empathy ability, and humanistic care quality are all at a moderately high level. Empathy ability plays a partially mediating role between medical narrative ability and humanistic care quality. It is suggested that clinicians’ medical narrative competence should be improved through various ways, thereby improving their humanistic care quality.
10.Discussion on the meaning of "yinluo" in Suwen: Shuire Xue Lun.
Haoji WU ; Rui LI ; Zixuan ZHU ; Weijie QIU ; Shangjin LIU
Chinese Acupuncture & Moxibustion 2025;45(2):249-252
By analyzing the understandings of water points (acupoints connected with the kidney) and its association with water (kidney), zangfu organs and meridian-collateral recorded in Suwen: Shuire Xue Lun (Discussion on Water and Heat Diseases in Plain Question), it is found that the recognition on the water points is different from that on water diseases in Huangdi Neijing (the Yellow Emperor 's Inner Classic). The recognition on the water points focuses on the core theory, "rooted at the kidney", to explain the water diseases. Besides, in association with the study on the connotation of "luo" in Huangdi Neijing, it is discovered that "yinluo" discussed in water points is actually the misunderstanding of "zang zhi yinluo" that means "the connection by the kidney". It is shown that the discussion of water points refer to the elaboration of zangfu organs and 57 acupoints connected with water (the kidney), rather than the theory of collaterals. The characteristics of these 57 acupoints involved and the related needling techniques provide a new approach to the treatment of zangfu diseases.
Acupuncture Points
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Humans
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Meridians
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China
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History, Ancient
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Medicine in Literature
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Medicine, Chinese Traditional/history*
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Acupuncture Therapy/history*

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