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.Renshentang Alleviates Atherosclerosis in Mice by Targeting TRPV1 to Regulate Foam Cell Cholesterol Metabolism
Yulu YUAN ; Ce CHU ; Xuguang TAO ; Zhen YANG ; Xiangyun CHEN ; Zhanzhan HE ; Yongqi XU ; Yuxin ZHANG ; Peizhang ZHAO ; Wanping CHEN ; Hongxia ZHAO ; Wenlai WANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(17):11-19
ObjectiveTo explore the effects of Renshentang on atherosclerosis (AS) in mice based on the role of transient receptor potential vanilloid1 (TRPV1) in regulating cholesterol metabolism in foam cells. MethodsNine SPF-grade 8-week-old C57BL/6J mice were set as a normal group, and 60 ApoE-/- mice were randomized into model, positive drug (simvastatin, 0.02 g·kg-1·d-1), and low-, medium-, and high-dose (1.77, 3.54, 7.08 g·kg-1·d-1, respectively) Renshentang groups (n=12) according to body weight. The normal group was fed with a normal diet, and the other groups were fed with a high-fat diet and given corresponding drugs by oral gavage for the modeling of AS. The mice were administrated with corresponding drugs once a day for 12 weeks. After the last administration and fasting for 12 h, the aorta was collected. Plaque conditions, pathological changes, levels of total cholesterol (TC), triglcerides (TG), low-density lipoprotein-cholesterol (LDL-C), and high-density lipoprotein-cholesterol (HDL-C), and the expression of TRPV1, liver X receptor (LXR), inducible degrader of the low-density lipoprotein receptor (IDOL), and low-density lipoprotein receptor (LDLR) in the aortic tissue were observed and detected by gross oil red O staining, HE staining, Western blot, immunohistochemistry, and real-time PCR. ResultsCompared with the normal group, the model group presented obvious plaque deposition in the aorta, raised levels of TC, TG, and LDL-C in the serum (P<0.01), up-regulated expression level of LDLR in the aorta (P<0.01), lowered level of HDL-C in the serum, and down-regulated expression levels of TRPV1, LXR, and IDOL in the aorta (P<0.05, P<0.01). Compared with the model group, the positive drug and Renshentang at different doses alleviated AS, elevated the levels of HDL-C, TRPV1, LXR, and IDOL (P<0.05, P<0.01), while lowering the levels of TC, TG, LDL-C, and LDLR (P<0.05, P<0.01). ConclusionRenshentang has a lipid-lowering effect on AS mice. It can effectively reduce lipid deposition, lipid levels, and plaque area of AS mice by activating TRPV1 expression and regulating the LXR/IDOL/LDLR pathway.
4.Renshentang Alleviates Atherosclerosis in Mice by Targeting TRPV1 to Regulate Foam Cell Cholesterol Metabolism
Yulu YUAN ; Ce CHU ; Xuguang TAO ; Zhen YANG ; Xiangyun CHEN ; Zhanzhan HE ; Yongqi XU ; Yuxin ZHANG ; Peizhang ZHAO ; Wanping CHEN ; Hongxia ZHAO ; Wenlai WANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(17):11-19
ObjectiveTo explore the effects of Renshentang on atherosclerosis (AS) in mice based on the role of transient receptor potential vanilloid1 (TRPV1) in regulating cholesterol metabolism in foam cells. MethodsNine SPF-grade 8-week-old C57BL/6J mice were set as a normal group, and 60 ApoE-/- mice were randomized into model, positive drug (simvastatin, 0.02 g·kg-1·d-1), and low-, medium-, and high-dose (1.77, 3.54, 7.08 g·kg-1·d-1, respectively) Renshentang groups (n=12) according to body weight. The normal group was fed with a normal diet, and the other groups were fed with a high-fat diet and given corresponding drugs by oral gavage for the modeling of AS. The mice were administrated with corresponding drugs once a day for 12 weeks. After the last administration and fasting for 12 h, the aorta was collected. Plaque conditions, pathological changes, levels of total cholesterol (TC), triglcerides (TG), low-density lipoprotein-cholesterol (LDL-C), and high-density lipoprotein-cholesterol (HDL-C), and the expression of TRPV1, liver X receptor (LXR), inducible degrader of the low-density lipoprotein receptor (IDOL), and low-density lipoprotein receptor (LDLR) in the aortic tissue were observed and detected by gross oil red O staining, HE staining, Western blot, immunohistochemistry, and real-time PCR. ResultsCompared with the normal group, the model group presented obvious plaque deposition in the aorta, raised levels of TC, TG, and LDL-C in the serum (P<0.01), up-regulated expression level of LDLR in the aorta (P<0.01), lowered level of HDL-C in the serum, and down-regulated expression levels of TRPV1, LXR, and IDOL in the aorta (P<0.05, P<0.01). Compared with the model group, the positive drug and Renshentang at different doses alleviated AS, elevated the levels of HDL-C, TRPV1, LXR, and IDOL (P<0.05, P<0.01), while lowering the levels of TC, TG, LDL-C, and LDLR (P<0.05, P<0.01). ConclusionRenshentang has a lipid-lowering effect on AS mice. It can effectively reduce lipid deposition, lipid levels, and plaque area of AS mice by activating TRPV1 expression and regulating the LXR/IDOL/LDLR pathway.
5.Application of self-transcendence in cancer patients: a scoping review
Zheng WANG ; Xia TIAN ; Yongqi HUANG ; Wenli XIAO
Chinese Journal of Modern Nursing 2024;30(6):825-831
Objective:To conduct a scoping review on self-transcendence in cancer patients, analyze and summarize the current status of self-transcendence in cancer patients, so as to provide a reference for its future development in cancer.Methods:The relevant research was systematically searched on China National Knowledge Infrastructure, WanFang Data, VIP, PubMed, Web of Science, Embase, Cochrane Library, and CINAHL, with a search period from database establishment to September 5, 2023. The included literature was summarized and analyzed.Results:A total of 43 articles were included, consisting of 16 cross-sectional surveys, 8 qualitative studies, and 19 intervention studies. Five aspects were elaborated and summarized, namely theoretical evolution and development, evaluation tools, current situation and influencing factors, implementation approaches, and intervention program characteristics.Conclusions:The research on self-transcendence in cancer patients is in the ascendant. In the future, it is necessary to strengthen the development of self-transcendence assessment tools for cancer patients, adopt various research methods to comprehensively understand the changes in self-transcendence level and psychological experience of cancer patients, and improve the scientific and rigorous nature of self-transcendence intervention program for cancer patients.
6.Development and validation of a prediction model for abnormal bone mass in end-stage renal disease patients
Jing LU ; Yujia WANG ; Yuxia ZHANG ; Zhiqing CHEN ; Yongqi LI ; Min WU ; Rining TANG
Chinese Journal of Nephrology 2024;40(5):345-357
Objective:To identify the risk factors, and develop and validate a risk prediction model for abnormal bone mass in end-stage renal disease (ESRD) patients.Methods:It was a retrospective cross-sectional study. The clinical and laboratory data of ESRD patients who were hospitalized in the Department of Nephrology, Zhongda Hospital Affiliated to Southeast University from January 2022 to May 2023 were collected retrospectively. The patients were randomly divided into training and validation cohorts at a ratio of 7∶3. They were further divided into normal and abnormal bone mass groups according to the T value measured by dual-energy X-ray absorptiometry (DXA). Then, backward stepwise regression and least absolute shrinkage and selection operator (LASSO) were respectively used to develop the risk prediction model for abnormal bone mass in ESRD patients. Akaike information criterion (AIC), bayesian information criterion (BIC), and accuracy were used to evaluate the performance of these two models, after which the preferable model was selected. Moreover, the receiver operating characteristic (ROC) curve, calibration curve, Hosmer-Lemeshow test, and decision curve analyses (DCA) were applied to evaluate the diagnostic performance of the preferable model. Finally, a dynamic nomogram for individual assessment was constructed based on the preferable model.Results:A total of 254 ESRD patients were enrolled, including 160 (63.0%) males, 161 (63.4%) hemodialysis patients, and 202 (79.5%) patients with abnormal bone mass. There was no significant difference in the prevalence of abnormal bone mass between training group ( n=178) and validation group ( n=76) (79.2% vs. 80.3%, χ2=0.036, P=0.849). The final variables and variable parameters included in the LASSO and stepwise regression models were the same, which were five variables: age, body mass index, hypertension, diabetes, and osteocalcin. Both models also had the same AIC, BIC, and accuracy in the training group, which were 113.45, 132.54, and 0.837, respectively. Therefore, the LASSO model and the stepwise regression model performed consistently in this study and could be considered as the same model, hereafter referred to as the Model. The Model's area under the ROC curve in the training and validation groups was 0.923 (95% CI 0.884-0.963) and 0.809 (95% CI 0.675-0.943), respectively. The optimal cutoff for the training group was 0.858, with a sensitivity of 0.801, a specificity of 0.973 and an accuracy of 0.837; when this cutoff value was taken, the validation group's sensitivity was 0.689, specificity was 0.800, and accuracy was 0.711. The Model demonstrated excellent performance in the calibration curve, Hosmer-Lemeshow test ( P>0.05), and DCA. Finally, based on the five predictors of the Model, a dynamic nomogram was created for clinicians to enter baseline clinical parameters for early identification of high-risk patients with abnormal bone mass. Conclusions:A dynamic nomogram for abnormal bone mass in ESRD patients is constructed with good predictive performance based on the prediction model, which can be used as a practical approach for the personalized early screening and auxiliary diagnosis of the potential risk factors and assist physicians in making a personalized diagnosis for patients.
7.A single-center retrospective study of salvage allogeneic hematopoietic stem cell transplantation pretreated with MeCBA regimen for refractory/relapsed acute myeloid leukemia
Fangfang YUAN ; Yongqi WANG ; Minghui LI ; Gangping LI ; Ziye LI ; Ruihua MI ; Qingsong YIN ; Yuewen FU ; Xudong WEI
Chinese Journal of Hematology 2024;45(5):500-504
Thirty refractory relapsed acute myeloid leukemia (R/R AML) patients who received salvage allo-HSCT with MeCBA conditioning regimen from January 2018 to June 2022 at Henan Cancer Hospital were included, and their clinical data were reviewed. There were 16 males and 14 females among the 30 patients with a median age of 37 (16-53) years. There were 3 sibling allograft donor transplants, 1 unrelated donor transplant, and 26 haplotype transplants. The median course of pre-transplant chemotherapy was 4 (3-22). The time of neutrophil engraftment was 14 (9-22) days and 18 (10-40) days for platelet. The 30-day cumulative incidence of neutrophil engraftment was 100% and the 100-day cumulative incidence of platelet engraftment was 96.7% (95% CI 85.4% -97.5% ). 22 (73.3% ) patients experienced grade 1-2 gastrointestinal reactions, and there was no grade 3-4 organ toxicity. With a median follow-up of 37.1 months, the overall survival (OS) rate, event-free survival (EFS) rate, cumulative recurrence rate (CIR), and non-recurrence mortality (NRM) rate at 3 years after transplantation were 70.0% (95% CI 50.3% -83.1% ), 65.3% (95% CI 44.8% -79.8% ), 21.2% (95% CI 9.2% -44.4% ) and 16.7% (95% CI 7.3% -35.5% ), respectively.
8.Multidimensional screening of Astragalus membranaceus small molecules to mitigate carbon ion radiation-induced bystander effects
Zhang LIYING ; Zhang YIMING ; Li YANGYANG ; Li QIYANG ; Zhang SHANGZU ; Miao ZHIMING ; He JINPENG ; Zhou TING ; Yang GENGQIANG ; Wang XIN ; Wang JUFANG ; Liu YONGQI
Journal of Pharmaceutical Analysis 2024;14(10):1531-1534
Existing studies have shown that Astragalus membranaceus(AM)and its active ingredients astragalus polysaccharides,oninon,and astragalus methyl glycosides can attenuate X-ray radiation-induced injury.However,there are no studies on how isoliquiritigenin(ISL)attenuate the bystander effect of bone marrow mesenchymal stem cells(BMSCs)induced by carbon ion radiation therapy for lung cancer.This study aimed to investigate the AM-derived small molecule ISL to enhance radiotherapy sensitivity by attenuating the carbon ion radiation-induced bystander effect(RIBE)in BMSCs to elucidate its mecha-nism of action.In this study,we established a C57BL/6 mouse lung cancer transplantation tumor model in vivo and a co-culture model of A549 cells and BMSCs in vitro,and the models were successfully treated with carbon ions.In further work,we used flow cytometry,immunofluorescence,Western blot,enzyme-linked immunosorbent assay(ELISA),inhibitor,short hairpin RNA(shRNA),Cell Counting Kit-8(CCK-8),and other methods to illustrate the mechanism.In the next experiments,we found that ISL combined with carbon ion radiotherapy had a significant anti-tumor effect and protected BMSCs from radiation damage.The aim of this study was to investigate the potential of ISL in enhancing the sensitivity of lung cancer cells to radiotherapy and attenuating RIBE in both in vitro and in vivo settings.Traditional Chinese medicine combined with radiation therapy is a promising and innovative treatment for non-small cell lung cancer.These results establish a theoretical foundation for further clinical development of ISL as a potential radiosensitizer option.
9.Comparison of Runzao Zhiyang capsules and loratadine tablets in drug-induced liver injury:a real-world cohort study
Zilin LONG ; Houyu ZHAO ; Yongqi ZHENG ; Lianxin WANG ; Feng SUN
Chinese Journal of Pharmacoepidemiology 2024;33(3):241-250
Objective To compare the difference in risk of drug-induced liver injury(DILI)between Runzao Zhiyang capsules and loratadine tablets.Methods Based on electronic medical records obtained through active drug safety monitoring in China,a retrospective cohort study was conducted to collect clinical data of patients who took oral Runzao Zhiyang capsules or loratadine tablets between January 1,2004,and December 31,2021.After balancing the confounding factors with a 1∶1 propensity score,the logistic regression model was used to analyze the risk of DILI between the two groups.Additionally,the sensitivity analysis of the data before matching and after inverse probability weighting method was conducted.Results A total of 31 636 patients were included,with 26 840 patients taking Runzao Zhiyang capsules orally.After matching there were 4 072 patients in each group,the risk of DILI in the Runzao Zhiyang capsules group was significantly lower than in the loratadine tablets group(0.12%vs.0.83%),OR=0.15(95%CI 0.06 to 0.38).Before matching and after inverse probability weighting,the incidence of DILI in the Runzao Zhiyang capsules group was still lower than that in the loratadine tablets group,and the difference was statistically significant(P<0.001).Conclusion Runzao Zhiyang capsules have a better safety profile in terms of liver injury compared to the loratadine tablets.The hepatotoxicity of Polygonum multiflorum and its preparations should be scientifically evaluated and rationally treated to ensure medication safety and health.
10.Finite element analysis of the effects of posterior malleolar fracture fixation on the rotational stability of the ankle joint
Yongqi LI ; Yi LIAO ; Zhou FANG ; Shun WANG ; Tian ZHAO ; Huaqian LA ; Nati SHA ; Yunfeng YANG
Chinese Journal of Trauma 2024;40(8):707-714
Objective:To explore the effects of posterior malleolar fracture fixation on the rotational stability of the ankle joint.Methods:A total of 20 fresh cadaveric specimens of lower limbs were anatomized to measure the area of attachment of the posterior inferior tibiofibular ligament and transverse ligament complex to the posterior surface of the tibia. One healthy volunteer was selected to construct a finite element model for the intact tibiofibular and ankle joints and finite element models for posterior malleolar fracture with different posterior projection areas. A load of 600 N was vertically applied to the inferior calcaneus along the tibial mechanical axis. The contact area and maximum Von Mises stress of the distal tibial articular surface were analyzed to verify the validity of the model for the intact tibiofibular and ankle joints. In the finite element models for the posterior malleolar fracture (S, 1/2S, 1/4S, 1/8S and 1/16S model groups, with S standing for the complete projection area of the ligament complex on the posterior surface of the tibia), the width increase in the tibiofibular clear space was measured when a vertical load of 600 N and external rotation load of 5 N·m were applied to the ankle joint after the reduction and fixation of posterior malleolar fracture. The cutoff value of the posterior projection area of posterior malleolar fracture that could maintain the rotational stability of the ankle joint was assessed.Results:The measurement results of the cadaveric specimens showed that the area of attachment of the posterior inferior tibiofibular ligament and transverse ligament complex to the posterior surface of the tibia was relatively large. It was attached to the posterolateral area of the distal tibia with the highest point located at (45.2±5.6)mm from the articular surface. With the increase in the distance from the joint line, the width of the posterior attachment area of the ligament complex was decreased. Results of the finite element analysis showed that in the finite element model for the intact tibiofibular and ankle joints, the tibiotalar joint contact area was 324.02 mm 2 and the maximum Von Mises stress was 4.495 1 MPa with a vertical load of 600 N. In the finite element models for the posterior malleolar fracture, the distal tibiofibular clear spaces of the S, 1/2S, 1/4S and 1/8S model groups increased by less than 2 mm following loading, while it was increased by 3.445 8 mm in the 1/16S model group. The cutoff value of the posterior tibial projection area that could maintain the rotational stability of the ankle joint was 1/8S. Conclusions:The attachment area of the posterior inferior tibiofibular ligament and transverse ligament complex to the posterior surface of the tibia is large. Both the axial stability and rotational stability of the ankle joint should be considered in the treatment selection for posterior malleolar fracture. Simple posterior malleolar fixation is recommended to restore the rotational stability and axial stability of the ankle joint when tibiofibular syndesmosis is unstable and the cutoff value is larger than or equal to 1/8, while tibiofibular syndesmosis screws must be implanted when tibiofibular syndesmosis is unstable and the cutoff value is less than 1/8.

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