1.Inhibition of Angiogenesis by Sanguisorbae Radix and Sophorae Flos in Ulcerative Colitis Mice by Regulating PI3K/Akt Signaling Pathway
Yuzhuo WEI ; Li LIU ; Shu BU ; Yongqi WANG ; Zhiwei MIAO ; Yi XU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(11):40-50
ObjectiveTo explore the potential mechanism of action of the combination of Sanguisorbae Radix-Sophorae Flos (DH) in the treatment of ulcerative colitis (UC) using network pharmacology methods and molecular docking technology. MethodsNetwork pharmacology analysis was utilized to predict the potential targets of DH for the treatment of UC. The therapeutic effects were experimentally validated by inducing a UC model in mice with 3% dextran sulfate sodium (DSS). The experimental groups were the normal group, the model group, the salazosulfapyridine group (100 mg·kg-1), and the low, medium, and high dose groups of DH (1.2, 2.4, and 4.8 g·kg-1). The efficacy of the treatment was assessed through the general condition of the mice, histopathological examination, and the expression levels of inflammatory markers in the colon. The effect of DH on angiogenesis was explored by messenger RNA (mRNA) detection of colonic angiogenesis-related mediators, vascular endothelial growth factor (VEGF) immunohistochemistry, microvessel density (MVD) detection, and transmission electron microscopy. The phosphatidylinositol-3-kinase (PI3K)-protein kinase B (Akt) signaling pathway proteins were quantitatively analyzed through Western blot to assess whether the suppression of pathological angiogenesis by DH is associated with this pathway. ResultsNetwork pharmacological analysis yielded 112 potential core therapeutic targets for the treatment of UC with DH, of which the core targets were tumor protein 53 (TP53), JUN, interleukin (IL)-6, Akt1, and tumor necrosis factor (TNF). Compared with the normal group, mice in the model group showed significant weight loss, colon shortening, and high DAI score, increased expression of inflammatory factors IL-6, IL-1β, and TNF-α, as well as increased mRNA expression levels of angiogenesis-related mediators VEGF, vascular cell adhesion molecule 1 (VCAM1), angiotensin 1 (Ang1), matrix metalloproteinase (MMP)-1, MMP-2, and MMP-9. The positive expression of CD31 and VEGF in colonic tissue increased, and the protein expression of the PI3K/Akt pathway was increased (P<0.05). The endothelial cells of the colonic mucosa and the colonic vasculature were severely damaged. Compared with the model group, mice in the DH groups had significantly reduced weight loss and colon shortening, lower DAI scores, and a significant decrease in mRNA expression of inflammatory factors and angiogenesis-related mediators. In addition, there was decreased positive expression of CD31 and VEGF in colonic tissue and decreased protein expression of the PI3K/Akt pathway (P<0.05). ConclusionNetwork pharmacology, molecular docking, and experimental validation are applied to explore the mechanism of action of DH in the treatment of UC, and it is found that DH is able to improve the symptoms of colitis and inhibit the pathological angiogenesis in UC mice. Its action might be related to affecting the PI3K/Akt pathway.
2.Inhibition of Angiogenesis by Sanguisorbae Radix and Sophorae Flos in Ulcerative Colitis Mice by Regulating PI3K/Akt Signaling Pathway
Yuzhuo WEI ; Li LIU ; Shu BU ; Yongqi WANG ; Zhiwei MIAO ; Yi XU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(11):40-50
ObjectiveTo explore the potential mechanism of action of the combination of Sanguisorbae Radix-Sophorae Flos (DH) in the treatment of ulcerative colitis (UC) using network pharmacology methods and molecular docking technology. MethodsNetwork pharmacology analysis was utilized to predict the potential targets of DH for the treatment of UC. The therapeutic effects were experimentally validated by inducing a UC model in mice with 3% dextran sulfate sodium (DSS). The experimental groups were the normal group, the model group, the salazosulfapyridine group (100 mg·kg-1), and the low, medium, and high dose groups of DH (1.2, 2.4, and 4.8 g·kg-1). The efficacy of the treatment was assessed through the general condition of the mice, histopathological examination, and the expression levels of inflammatory markers in the colon. The effect of DH on angiogenesis was explored by messenger RNA (mRNA) detection of colonic angiogenesis-related mediators, vascular endothelial growth factor (VEGF) immunohistochemistry, microvessel density (MVD) detection, and transmission electron microscopy. The phosphatidylinositol-3-kinase (PI3K)-protein kinase B (Akt) signaling pathway proteins were quantitatively analyzed through Western blot to assess whether the suppression of pathological angiogenesis by DH is associated with this pathway. ResultsNetwork pharmacological analysis yielded 112 potential core therapeutic targets for the treatment of UC with DH, of which the core targets were tumor protein 53 (TP53), JUN, interleukin (IL)-6, Akt1, and tumor necrosis factor (TNF). Compared with the normal group, mice in the model group showed significant weight loss, colon shortening, and high DAI score, increased expression of inflammatory factors IL-6, IL-1β, and TNF-α, as well as increased mRNA expression levels of angiogenesis-related mediators VEGF, vascular cell adhesion molecule 1 (VCAM1), angiotensin 1 (Ang1), matrix metalloproteinase (MMP)-1, MMP-2, and MMP-9. The positive expression of CD31 and VEGF in colonic tissue increased, and the protein expression of the PI3K/Akt pathway was increased (P<0.05). The endothelial cells of the colonic mucosa and the colonic vasculature were severely damaged. Compared with the model group, mice in the DH groups had significantly reduced weight loss and colon shortening, lower DAI scores, and a significant decrease in mRNA expression of inflammatory factors and angiogenesis-related mediators. In addition, there was decreased positive expression of CD31 and VEGF in colonic tissue and decreased protein expression of the PI3K/Akt pathway (P<0.05). ConclusionNetwork pharmacology, molecular docking, and experimental validation are applied to explore the mechanism of action of DH in the treatment of UC, and it is found that DH is able to improve the symptoms of colitis and inhibit the pathological angiogenesis in UC mice. Its action might be related to affecting the PI3K/Akt pathway.
3.Study on the mechanism of Lycium barbarum polysaccharides inhibiting the proliferation,migration and immune escape of oral cancer cells
Jinyu LI ; Xiaoyu XU ; Yuzhuo WANG
China Pharmacy 2025;36(17):2134-2140
OBJECTIVE To explore the effects of Lycium barbarum polysaccharides on the proliferation, migration, and immune escape of oral cancer cells by regulating the T cell immunoglobulin and mucin domain-containing protein 3 (TIM3)/ galectin-9 (Gal-9) signaling pathway. METHODS Human oral cancer cells KB and CAL27 were assigned to control group, L. barbarum polysaccharides low-concentration group (200 μg/mL), L. barbarum polysaccharides high-concentration group (400 μg/mL), pcDNA-NC group (transfection of pcDNA-NC plasmid), pcDNA-TIM3 group (transfection of pcDNA-TIM3 plasmid), high concentration of L. barbarum polysaccharides+pcDNA-NC group (400 μg/mL L. barbarum polysaccharides + transfection of pcDNA-NC plasmid), and high concentration of L. barbarum polysaccharides+pcDNA-TIM3 group (400 μg/mL L. barbarum polysaccharides + transfection of pcDNA-TIM3 plasmid). The proliferation, migration and invasion abilities of the cells, T cell killing rate as well as the levels of interferon-γ (IFN-γ) and interleukin-2 (IL-2) in the cell supernatant were measured. mRNA expressions of TIM3 and Gal-9 and protein expressions of indoleamine 2,3-dioxygenase 1 (IDO1), programmed death-ligand 1 (PD-L1), TIM3 and Gal-9 in the cells were also determined. RESULTS Compared with control group, the clone formation rate, scratch healing rate, the number of invasive cells, protein expressions of IDO1 and PD-L1, mRNA and protein expressions of TIM3 and Gal-9 in both cell types of L. barbarum polysaccharide low- and high-concentration groups were decreased significantly (P<0.05), while the proliferation inhibition rate, T cell killing rate, and the levels of IFN-γ and IL-2 were significantly increased (P<0.05). Compared with control group and pcDNA-NC group, the clone formation rate, scratch healing rate, the number of invasive cells, and protein expressions of IDO1 and PD-L1, mRNA and protein expressions of TIM3 and Gal-9 in both cell types of the pcDNA-TIM3 group were all significantly increased (P<0.05), while the proliferation inhibition rate, T cell killing rate, IFN-γ and IL-2 levels were significantly decreased (P<0.05). Compared with L. barbarum polysaccharides high-concentration group and high concentration of L. barbarum polysaccharides+pcDNA-NC group, the clone formation rate, scratch healing rate, the number of invasive cells, and protein expressions of IDO1 and PD-L1, mRNA and protein expressions of TIM3 and Gal-9 in both cell types of high concentration of L. barbarum polysaccharides+pcDNA-TIM3 group were significantly increased (P<0.05), while the proliferation inhibition rate, T cell killing rate, and the levels of IFN-γ and IL-2 were significantly decreased (P<0.05). CONCLUSIONS L. barbarum polysaccharides may inhibit the proliferation, migration, and immune escape of oral cancer cells by suppressing TIM3/Gal-9 signaling pathway.
4.Breaking the ethical dilemmas in elderly care institutions under the integrated medical and elderly care model: exploration and optimization of practical pathways
Xiangyan FENG ; Lele MIAO ; Qingqiao LYU ; Xiaoe LI ; Zhinan YANG ; Yuzhuo MA
Chinese Medical Ethics 2025;38(10):1270-1274
The integrated medical and elderly care model provides comprehensive medical and elderly care services by establishing medical facilities in elderly care institutions or forming close cooperative relationships with surrounding medical institutions. Currently, there are 87,000 paired partnerships established nationwide between medical and health institutions and elderly care service institutions, and more than 7,800 integrated medical and elderly care institutions have obtained the qualifications of medical and health institutions and completed elderly care service registration. This model not only meets the elderly’s healthcare needs but also provides life care, psychological support, and social activities, thereby improving their quality of life. However, the integrated medical and elderly care model also faces numerous ethical dilemmas in practice. This paper aimed to explore in depth the ethical dilemmas and countermeasures optimization in the work of elderly care institutions under this model, to promote the improvement of service quality, comprehensively guarantee the rights and interests of the elderly, and promote the healthy development of this model in practice. Under this model, the elderly care institutions not only bear the responsibility of providing long-term care and life services but also need to cooperate with medical institutions to provide healthcare and health management services for the elderly. By exploring the practical paths for elderly care institutions to address the ethical dilemmas faced with this model, feasible solutions were proposed to enhance the welfare of the elderly and promote the harmonious development of society.
5.Effect of moxibustion at "Shenque" (CV8) on the expression of BDNF and c-fos in the urinary control brain regions of rats with neurogenic bladder after spinal cord injury.
Han YU ; Yuanbo FU ; Huilin LIU ; Yuzhuo ZHANG ; Yutong NI ; Qingdai LI ; Yi XU
Chinese Acupuncture & Moxibustion 2025;45(5):638-645
OBJECTIVE:
To observe the effects of moxibustion at "Shenque" (CV8) on urodynamics and the expression of brain-derived neurotrophic factor (BDNF) and immediate early gene (c-fos) in pontine micturition center (PMC), periaqueductal gray (PAG), medial prefrontal cortex (mPFC) of neurogenic bladder (NB) rats after spinal cord injury.
METHODS:
Twenty-four SPF female SD rats were randomly divided into a sham-operation group (6 rats) and a modeling group (18 rats). In the modeling group, T9 complete spinal cord transection method was used to establish a neurogenic detrusor overactivity model, and the 12 rats with successful modeling were randomized into a model group and a moxibustion group, with 6 rats in each group. The rats in the moxibustion group were treated with ginger/salt-insulated moxibustion at "Shenque" (CV8), and 4 consecutive moxa cones were delivered in one intervention. Moxibustion was operated once daily and for 14 days. After intervention completion, the urodynamic indexes of rats in each group were detected. Fluorescence quantitative PCR was used to detect the mRNA expression of BDNF and c-fos in PMC, PAG and mPFC in rats. Western blot was used to detect the protein expression of BDNF and c-fos in PMC, PAG and mPFC.
RESULTS:
The rats in the sham-operation group did not show phasic detrusor contraction during bladder filling. Compared with the model group, the frequency and amplitude of the phasic detrusor contraction were reduced 5 min before urine leakage in the rats of the moxibustion group (P<0.05), and the duration of the first phasic detrusor contraction during bladder filling was prolonged (P<0.05). Compared with the sham-operation group, the mRNA and protein expression of BDNF and c-fos in PMC, PAG and mPFC increased in the model group (P<0.05). Compared with the model group, the mRNA and protein expression of BDNF and c-fos in PMC, PAG and mPFC decreased in the moxibustion group (P<0.05).
CONCLUSION
Moxibustion at "Shenque" (CV8) can improve the phasic contraction during bladder filling in NB rats after spinal cord injury, possibly by down-regulating the mRNA and protein expression of BDNF and c-fos in PMC, PAG, and mPFC.
Animals
;
Moxibustion
;
Female
;
Rats
;
Brain-Derived Neurotrophic Factor/metabolism*
;
Rats, Sprague-Dawley
;
Acupuncture Points
;
Spinal Cord Injuries/metabolism*
;
Urinary Bladder, Neurogenic/etiology*
;
Proto-Oncogene Proteins c-fos/metabolism*
;
Humans
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Urinary Bladder/physiopathology*
;
Brain/metabolism*
;
Urination
7.Characterizing immune microenvironment cell composition of chronic rhinosinusitis with nasal polyps based on mass cytometry technology
Lei WANG ; Weiqing WANG ; Surita AODENG ; Yuzhuo LIU ; Zhenzhen ZHU ; Jingjing LI ; Wei LYU
Chinese Journal of Otorhinolaryngology Head and Neck Surgery 2024;59(6):532-542
Objective:To analyze the cellular composition characteristics of the nasal tissue immune microenvironment in patients with control, chronic rhinosinusitis without nasal polyps (CRSsNP), non-eosinophilic chronic rhinosinusitis with nasal polyps (neCRSwNP), and eosinophilic chronic rhinosinusitis with nasal polyps (eCRSwNP) using mass cytometry flow technology.Methods:Thirteen CRS patients who underwent endoscopic nasal surgery at the Department of Otorhinolaryngology Head and Neck Surgery of Peking Union Medical College Hospital from March to December 2022 were recruited, including 8 males and 5 females, aged 22.3 to 58.3 years. Three control mucosae were obtained from normal ethmoid or sphenoid sinuses of patients with benign tumors of the temporal fossa or non-functional pituitary adenomas who underwent endoscopic surgery, excluding allergic rhinitis and sinusitis. Sixteen clinical tissue samples (3 of control, 3 of CRSsNP, 4 of neCRSwNP, and 6 of eCRSwNP) were prepared into single-cell suspensions. Mass cytometry flow detection was performed using a combination of 42 molecular markers to analyze the differences in cell subpopulations among the groups. Data were analyzed using GraphPad Prism 9.Results:Based on the mass cytometry flow results, cells from control, CRSsNP, neCRSwNP, and eCRSwNP were divided into seven main cell subgroups, with detailed subgrouping of T/NK cells and myeloid cells. In T/NK cells, compared with the control group, the number of NK CD56bright cells increased in the CRSsNP group, while NK CD56dim cells decreased; compared with the CRSsNP group, the eCRSwNP group showed a decrease in NKT cells and CD4 +Tem cells; compared with the CRSsNP group, the eCRSwNP group showed a significant increase in CD25 expression within Treg cells; compared with the CRSsNP group, the eCRSwNP group showed a significant decrease in Tbet expression in CD8 +Teff cells and CD8 +TRM cells; in eCRSwNP, the expression of CD103 in CD8 +TRM cells was significantly lower than in CRSsNP. In myeloid cells, compared with the other three groups, the eCRSwNP group showed a significant increase in macrophages and a significant decrease in cDC1 and monocytes; compared with the control group and CRSsNP, the eCRSwNP group also showed a significant decrease in resting state macrophages; compared with the CRSsNP group, the eCRSwNP group showed a significant decrease in the level of CX3CR1 within cDC2 and monocytes; the expression levels of NLRP3 in cDC2 and macrophages in the eCRSwNP group were significantly higher than in the other three groups; compared with the control group, the expression levels of Gata3 in cDC2 and macrophages in the eCRSwNP group were also significantly increased; additionally, the expression of CCR2 within monocytes in the eCRSwNP group was lower than in the CRSsNP group. In ILC, compared with the control group, the expression of CCR6 decreased in the eCRSwNP group. Conclusions:Compared with the control group, CRSsNP, and neCRSwNP, eCRSwNP shows an increase in macrophage number, a decrease in cDC1 and resting state macrophages, and depletion of protective cells CD103 +CD8 +TRM. Additionally, the expression levels of CCR2 and CX3CR1 in monocytes of eCRSwNP are decreased.
8.Evaluation of student experience teaching in medical colleges and universities under the three-source flow theory: proposal of core concepts and framework construction
Yuzhuo XIE ; Yong LI ; Xilin XU ; Yazhou WANG ; Yuwei ZHANG ; Mingli JIAO
Chinese Journal of Medical Education Research 2024;23(7):865-871
In the context of the emphasis on the claims of multiple subjects in fourth-generation educational evaluation, the subjective experience of students has gradually become one of the key contents of educational evaluation. However, there is still a vague understanding of the conceptual source, specific definition, and measurement indicators of the student experience theory, and a more systematic theoretical system has not yet been formed. With the UE user experience thinking in the business field as the core meta-theory, this article integrates value-added evaluation and the idea of three-source flow, elaborates on the core concept connotation of compound student experience teaching evaluation, and builds a five-dimensional evaluation model for student experience with "aesthetic experience, interactive experience, emotional experience, behavioral experience, and discursive experience" as the first-level indicators based on literature research, expert interviews, and multi-round group discussions. It is hoped that student evaluation will force teachers to improve the contents and form of teaching and help to achieve breakthrough reform of the teaching system as a whole.
9.Study on risk factors for coma in patients with hypoglycemia
Quanhong LIN ; Yaowei XU ; Yuzhuo LI ; Lebai LIU ; Shifan TANG ; Xiaowan LIN ; Zhaohua XIN
Chinese Journal of Emergency Medicine 2024;33(9):1273-1280
Objective:To investigate the incidence and risk factors of coma in patients with hypoglycemia (≤3.9 mmol/L).Methods:A retrospective study was conducted. Patients aged 20 years and older with blood glucose levels ≤3.9 mmol/L, and measured by emergency physicians from January 2020 to December 2022 were collected. Baseline patient data, clinical values collected on-site, and treatment outcomes were analyzed. The Glasgow Coma Scale (GCS) was used to determine if patients were comatose, with GCS ≤8 classified as the coma group and GCS >8 as the non-coma group. Further analysis was conducted on the resuscitated coma group to identify factors affecting patient recovery. Patients were divided into eight age groups, seven time periods within 24 h, and six blood glucose level groups to calculate the incidence of coma. A multivariate logistic regression model was constructed to analyze independent risk factors for coma in hypoglycemic patients.Results:A total of 754 patients with blood glucose levels ≤3.9 mmol/L were collected, with 425 cases of coma and 329 non-coma cases, resulting in a coma probability of 56.37% (95% CI: 52.82%-59.91%). Patients in the coma group were older ( P<0.001) and had a higher prevalence of diabetes compared to the non-coma group (82.12% vs. 67.78%, P<0.001). The age of all patients was (73.05±15.20) years, with the 61-90 years age groups being the most prone to hypoglycemia and coma. In terms of time distribution, the high-incidence periods for hypoglycemia and coma were 0-6 o’clock, 6-9 o’clock, and 14-18 o’clock. The primary causes of hypoglycemia included reduced energy intake after insulin injection (12.07%), improper use of insulin (6.37%), and reduced energy intake (6.23%), with 71.09% of cases having unknown causes. Additionally, 18.44% of patients used insulin before the onset of hypoglycemia, with a higher proportion in the coma group compared to the non-coma group (22.12% vs. 13.68%, P=0.003). The initial blood glucose level of all patients was (2.13±0.85) mmol/L, with lower levels observed in the coma group compared to the non-coma group ( P<0.001). The probabilities of coma occurrence corresponding to blood glucose levels were: 1.1-1.5 mmol/L (72.97%), 1.6-2.0 mmol/L (68.90%), 2.1-2.5 mmol/L (54.10%), 2.6-3.0 mmol/L (38.20%), 3.1-3.5 mmol/L (37.50%), and 3.6-3.9 mmol/L (19.40%). Multivariate logistic regression analysis indicated that age ( OR=1.021, 95% CI: 1.010-1.033, P<0.001), insulin use before onset ( OR=1.948, 95% CI: 1.142-3.323, P=0.014), and blood glucose concentration ( OR=0.426, 95% CI: 0.347-0.522, P<0.001) were independent predictors of coma in hypoglycemic patients. The investigation revealed that after intravenous injection of 50% glucose solution, 215 of 425 coma patients regained consciousness (50.58%), and the recovery time was (18.43±9.09) min. Patients in the recovery group were younger and had lower initial blood glucose levels compared to the non-recovery group (both P<0.05), while recovery group re-measured blood glucose levels were higher than those in the non-recovery group ( P=0.002). Conclusions:The probability of coma in hypoglycemic patients was high, with insulin use being a common trigger. Proper use of insulin is essential to prevent hypoglycemia and coma.
10.Clinical experience in treatment of refractory tinnitus with He's santong therapy of acupuncture.
Xueting ZHANG ; Baijie LI ; Huilin LIU ; Yuzhuo ZHANG ; Yutong NI ; Yuhan ZENG ; Yaohui FENG ; Yuanbo FU
Chinese Acupuncture & Moxibustion 2024;44(11):1324-1327
This article summarizes the clinical experience in treatment of refractory tinnitus with He's santong therapy of acupuncture (three techniques of acupuncture to remove the blockage and promote circulation). Refractory tinnitus is characterized by a mixture of deficiency and excess, which is implicated in the dysfunction of zangfu organs, resulting in physical and mental injuries. In association with the complicated conditions of the diseases and etiology, He's santong therapy of acupuncture is adopted. The needling with filiform needles acts directly on the affected site to regulate the mind and improve the hearing, the fire needling works on removing the refractory illness and blockage through heating up, and bloodletting on activating blood circulation and promoting qi flowing to eliminate the pathogens. The three techniques of acupuncture co-work on harmonizing the mind, promoting the circulations in the ear to stop tinnitus.
Humans
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Tinnitus/physiopathology*
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Acupuncture Therapy
;
Male
;
Middle Aged
;
Adult
;
Female
;
Acupuncture Points

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