1.Traditional Chinese Medicine Treats Diabetic Nephropathy via Pathways Related to Pyroptosis: A Review
Jintao SHI ; Zhiyi ZHANG ; Yunfei WEI ; Jiarui HAN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(3):290-300
Diabetic kidney disease (DKD), one of the leading causes of end-stage renal disease, shows increasing prevalence and mortality, seriously affecting the physical and mental health of patients. As a crucial link in the occurrence and development of DKD, pyroptosis can lead to kidney cell injury and inflammation through the abnormal activation of reactive oxygen species (ROS)/thioredoxin-interacting protein (TXNIP)/NOD-like receptor protein 3 (NLRP3), Toll-like receptor 4 (TLR4)/nuclear factor-κB (NF-κB)/NLRP3, nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1), mitogen-activated protein kinase (MAPK)/NLRP3, and hypoxia-inducible factor-1α (HIF-1α)/NLRP3 signaling pathways, which accelerate the progression of DKD. In recent years, traditional Chinese medicine (TCM) has demonstrated definite efficacy in the treatment of DKD via multiple targets and pathways. Studies have shown that various TCM active components, including glycosides, flavonoids, polyphenols, terpenoids, and alkaloids, as well as TCM compound prescriptions for clearing heat and detoxifying, tonifying deficiency and consolidating root, and eliminating stasis and descending turbidity, can target relevant signaling pathways to inhibit pyroptosis and intervene in the development of DKD, providing new possibilities for precision treatment of DKD. This article systematically reviews the relevant pathways of pyroptosis and summarizes the research achievements and mechanisms of TCM active components and compound prescriptions in the treatment of DKD via pyroptosis in recent years. This review aims to provide new directions and ideas for the treatment and research of DKD with TCM and promote the modernization and development of TCM.
2.Treatment of Diabetic Kidney Disease with Traditional Chinese Medicine Based on Epithelial-to-mesenchymal Transition-related Pathways: A Review
Jintao SHI ; Zhiyi ZHANG ; Yushan GAO ; Baicun GUO ; Yifei HU ; Jiarui HAN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(24):288-298
Diabetic kidney disease (DKD) stands as one of the most prevalent microvascular complications of diabetes,noted for its concealed onset and tendency to evolve into end-stage renal disease,profoundly impacting patients' life expectancy and quality of life. Epithelial-to-mesenchymal transition (EMT) is a central pathological process in the initiation and progression of DKD,facilitating disease advancement and renal fibrosis,thus representing a crucial focus of research into the pathological mechanisms of DKD. EMT is driven by the abnormal activation of signaling pathways,including transforming growth factor-β (TGF-β)/Smad,secreted glycoprotein/β-catenin,Notch,tumor necrosis factor-α (TNF-α)/nuclear factor-κB (NF-κB),and phosphatidylinositol-3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR),leading to renal cellular injury and subsequently accelerating renal fibrosis and the progression of DKD. Traditional Chinese medicine (TCM),characterized by its multi-target and multi-pathway therapeutic approach,demonstrates unique advantages in addressing DKD and EMT. Recent research has shown that active ingredients in TCM,including glycosides,flavonoids,and polyphenols,as well as TCM formulas,can precisely target these relevant signaling pathways,effectively inhibiting cellular injury in DKD and intervening in the EMT process. These findings not only underscore the potential of TCM monomers and formulas in treating DKD and EMT but also pave new directions for research in this field within TCM. This paper systematically reviewed the signaling pathways associated with EMT and provided an in-depth analysis of the research achievements and underlying mechanisms of TCM monomers and formulas in treating DKD and intervening in EMT,aiming to offer new insights and directions for TCM in the treatment of DKD and research on EMT,thereby further promoting the modernization and development of TCM.
3.Progress in the treatment of Alzheimer′s disease by Chinese medicine extracts based on C . elegans model
Yuqing Pei ; Chunyu Xu ; Xindi Shao ; Yujie Zhu ; Siyue Zhou ; Zhiyi Zheng ; Fei Cheng ; Xuan Shi ; Zhangyue Chen
Acta Universitatis Medicinalis Anhui 2025;60(4):760-765
Abstract
Alzheimer′s disease(AD) is a common neurodegenerative disease. It has been found that AD is related to various pathogenic factors such as genetics, cardiovascular and cerebrovascular disease, and excessive phosphorylation of tau protein. However, no definitive conclusions on its pathogenesis have been reached. In this paper, the research progress on the pathogenesis of AD inC.elegansmodel and the therapeutic effects of traditional Chinese medicine extracts on AD are reviewed, providing a basis for further research on the alleviating effects of Chinese medicine extracts on AD.
4.Interleukin-27 exerts a protective effect against psoriasis by inhibiting the secretion of interleukin-17A from T cells: a mechanistic study
Zhiyi LAN ; Zeyu CHEN ; Zihan ZHAO ; Xilin ZHANG ; Jun GU ; Yuling SHI
Chinese Journal of Dermatology 2025;58(11):1034-1041
Objective:To investigate the specific mechanisms underlying the protective effect of interleukin (IL) -27 in the pathogenesis of psoriasis.Methods:Five skin tissue samples from healthy individuals and 6 lesional skin samples from psoriasis patients were collected, and IL-27 expression was determined by immunohistochemical staining. Il27ra gene knockout (KO) mice were constructed. Psoriasis-like mouse models were established with topical imiquimod in 5 wild-type (WT) mice and 6 KO mice. Mouse skin lesions were evaluated using the modified Psoriasis Area and Severity Index (mPASI), and lesional skin tissues were collected for hematoxylin and eosin (HE) staining to observe changes in epidermal thickness. Single-cell suspensions were prepared with skin lesions and skin-draining lymph nodes of 4 WT mice and 3 KO mice, and changes in immune cells (including T cells, γδ T cells, and neutrophils) were analyzed using flow cytometry. Additionally, skin-draining lymph node cells were isolated from 9 normal WT mice, and IL-17A expression was stimulated using a T-cell receptor agonist (CD3/28 activating antibodies, αCD3/28) or cytokines (IL-23 + IL-1β), followed by the addition of IL-27; peripheral blood mononuclear cells (PBMCs) were isolated from 6 psoriasis patients, and IL-17A expression was stimulated using the T-cell receptor agonist, followed by the addition of IL-27; the effect of IL-27 on IL-17A expression in T cells was analyzed using flow cytometry and enzyme-linked immunosorbent assay (ELISA). Measurement data were compared between two groups using the t test. Results:Immunohistochemical staining revealed a significant reduction in IL-27 expression in psoriatic lesions (mean fluorescence intensity: 9.85 ± 3.07) compared with the normal skin (19.45 ± 2.51, t = 5.60, P < 0.001). Animal experiments demonstrated that the KO mice exhibited significantly aggravated psoriasis-like skin inflammation (mPASI: 4.00 ± 0.89) and significantly increased epidermal thickness (115.50 ± 7.69 μm) compared with the WT mice (mPASI: 2.80 ± 0.84, t = 2.28, P = 0.049; epidermal thickness: 92.26 ± 8.76 μm, t = 4.70, P = 0.001) ; compared with the WT mice, the KO mice showed significantly increased proportions of T cells (11.22% ± 2.76% vs. 7.08% ± 0.85%) and dermal γδ T cells (4.78% ± 0.39% vs. 2.78% ± 0.49%) among live cells in the lesions ( t = 2.91, 2.75, respectively, both P < 0.05), as well as significantly increased proportions of Th17, IL-17 + γδ T, Th22, and IL-22 + γδ T cells in the skin-draining lymph nodes (all P < 0.05), but no significant difference in the proportion of neutrophils in the lesions (WT: 13.57% ± 8.36%, KO: 14.43% ± 9.13%; t = 0.13, P = 0.902). Experiments with different stimuli showed that IL-27 significantly suppressed T-cell receptor agonist-induced IL-17A expression in murine γδ T cells (αCD3/28 group: 1.00 ± 0.11, αCD3/28 + IL-27 group: 0.76 ± 0.13; t = 3.54, P = 0.004), while there was no significant difference in IL-17A expression between cells induced by IL-23 + IL-1β with the IL-27 co-culture and those without ( t = 1.34, P > 0.05). ELISA showed that IL-27 significantly reduced the IL-17A concentration in the culture supernatant of draining lymph node cells stimulated by the T-cell receptor agonist (αCD3/28 group: 1 535.00 ± 97.76 pg/ml, αCD3/28 + IL-27 group: 1 030.00 ± 287.90 pg/ml, t = 3.29, P = 0.031), but did not reduce the IL-17A concentration induced by IL-23 + IL-1β ( t = 0.09, P > 0.05). Flow cytometry indicated that IL-27 significantly inhibited the T-cell receptor agonist-induced IL-17A expression in T cells from psoriasis patients (αCD3/28 group: 4.28 ± 3.25, αCD3/28 + IL-27 group: 3.04 ± 2.65, t = 4.46, P = 0.007) . Conclusion:IL-27 appeared to play a protective role in psoriasis by suppressing IL-17A secretion from T cells.
5.Analysis of factors influencing postoperative pathological upgrading in prostate cancer with target biopsy Gleason score 3 + 3 and development of a predictive model
Rongjie SHI ; Lai DONG ; Zhiyi SHEN ; Kaiyu ZHANG ; Chenglong ZHANG ; Yamin WANG ; Ruizhe ZHAO ; Shangqian WANG ; Gong CHENG ; Lixin HUA
Chinese Journal of Urology 2025;46(9):684-690
Objective:To explore the influencing factors for pathological upgrading in prostate cancer patients with a Gleason score of 3 + 3 undergoing targeted biopsy,and to establish a nomogram prediction model.Methods:A retrospective analysis was conducted on 191 patients with localized prostate cancer diagnosed with a Gleason score of 3 + 3 through targeted biopsies at the First Affiliated Hospital of Nanjing Medical University from January 2020 to June 2024. The age of the patients was 67(61,73)years,with prostate-specific antigen(PSA)level of 7.44(5.53,10.19)ng/ml,prostate volume of 35.64(26.59,48.97)ml,and PSA density(PSAD)of 0.20(0.14,0.31)ng/ml 2. Among them,61 cases(31.94%)had a Prostate Imaging Reporting and Data System(PI-RADS)score of 3,104 cases(54.45%)had a score of 4,and 26 cases(13.61%)had a score of 5. The diameter of the main lesion was 10.75(7.86,14.00)mm. The lesions were located in the peripheral zone in 78 cases(40.84%),the transition zone in 99 cases(51.83%),and the anterior fibromuscular stroma in 14 cases(7.33%). The lesions were found at the apex in 56 cases(29.32%),in the body in 120 cases(62.83%),and at the base in 15 cases(7.85%). MRI revealed only one lesion with a PI-RADS score ≥ 3 in 131 cases,two suspected lesions in 43 cases,three suspected lesions in 12 cases,and four suspected lesions in 5 cases. Systematic biopsy was positive in 121 cases(63.4%)and negative in 70 cases(36.6%). The lesions were confined to the left lobe in 63 cases(32.98%),right lobe in 68 cases(35.60%),and involved both lobes in 60 cases(31.41%). The interval between biopsy and surgery was 9.0(7.0,14.0)days. Univariate analyses were performed using Mann-Whitney U tests or χ2 tests,and multivariate logistic regression was used to identify independent predictors of pathological upgrading. A nomogram model was constructed based on these independent predictors. The model’s discriminative ability was assessed using the area under the receiver operating characteristic(ROC)curve(AUC),and internal validation of the model’s consistency was conducted using the bootstrap resampling method. Decision curve analysis(DCA)was performed to assess clinical utility. Results:Among the 191 cases,60(31.4%)had no pathological upgrading after surgery,while 131(68.6%)showed upgrading. Univariate analysis showed that the maximum diameter of the main lesion[9.0(6.0,13.2)mm vs. 11.0(8.4,14.0)mm],number of suspicious lesions on MRI[1.0(1.0,1.0)vs. 1.0(1.0,2.0)],number of positive systematic biopsy cores[1.0(0,2.0)vs. 1.0(0,3.0)],percentage of positive systematic biopsy cores[0.08(0,0.17)vs. 0.12(0,0.25)],number of positive targeted biopsy cores[2.0(1.0,3.0)vs. 3.0(1.0,4.0)],percentage of positive targeted biopsy cores[0.37(0.24,0.75)vs. 0.50(0.38,0.85)],level of the index lesion,location of the index lesion,and PI-RADS score were associated with pathological upgrading( P < 0.05). Multivariate logistic regression analysis showed that PI-RADS score 4( OR = 5.88,95% CI 2.41 - 14.35),number of suspicious lesions on MRI( OR = 4.15,95% CI 1.88 - 9.17),location of the index lesion in the transition zone( OR = 6.86,95% CI 2.81 - 16.73),and percentage of positive targeted biopsy cores( OR = 4.37,95% CI 1.38 - 14.90)were independent risk factors for pathological upgrading( P < 0.05). The nomogram model constructed using these predictors had an AUC of 0.845. Internal validation using the Bootstrap method yielded an AUC value of 0.812,indicating high predictive accuracy of the model. The calibration curve indicated good calibration. Decision curve analysis showed that the threshold range for net benefit in the model was between 12% - 100%. Conclusions:The PI-RADS score 4,the number of lesions with PI-RADS ≥ 3,the location of the main lesion in the transition zone,and the percentage of positive needles in targeted biopsy are independent risk factors for pathological upgrading from Gleason score 3 + 3. The nomogram model constructed from these factors demonstrates good predictive performance and provides a reference for clinical decision-making.
6.Research on the anti-abortive effect of Taxilli Herba aqueous decoction in rats
Yao LIU ; Yinyue SHI ; Ying CUI ; Lingling LI ; Zhiyi FENG
Acta Laboratorium Animalis Scientia Sinica 2025;33(6):790-801
Objective To investigate the effect and mechanism of Taxilli Herba decoction in preventing miscarriage in rats with threatened abortion.Methods Seventy-two SPF-grade SD rats were co-housed at a male-to-female ratio of 2∶1.Forty-eight pregnant rats were subsequently divided into a normal group,a threatened abortion model group,a positive control group,as well as Taxilli Herba decoction low/medium/high dose groups(n=8 rats per group).Rats in the positive control group received 3.02 mg/kg dydrogesterone intragastrically,and rats in the low-,medium-,and high-dose Taxilli Herba decoction groups received 2.5,5,and 10 g/kg Taxilli Herba decoction intragastrically,respectively.The normal and model groups received intragastric distilled water once a day for 10 consecutive days.On day 10 after administration of the corresponding treatment,rats in all groups except the normal group received intragastric administration of 3.75 mg/kg mifepristone suspension.The effects of Taxilli Herba on the vaginal bleeding rate and abortion rate were observed.Serum levels of follicle-stimulating hormone(FSH),luteinizing hormone(LH),estrogen(E),progesterone(P),vascular endothelial growth factor(VEGF),testosterone(T),and aromatase and E and P levels in the ovary in pregnant rats were detected by enzyme-linked immunosorbent assay.Expression levels of E receptor(ER),P receptor(PR),VEGF receptor 2(VEGFR2),and platelet endothelial cell adhesion molecule-1(CD31)in the uterine decidua in pregnant rats were detected by immunofluorescence staining,and semi-quantitative analysis was performed.Results Mifepristone significantly increased the vaginal bleeding rate and abortion rate in pregnant rats,but these were effectively reduced by treatment with Taxilli Herba water decoction.Taxilli Herba water decoction also increased serum E,P,and VEGF,and ovary levels of E and P(P<0.05).The treatment also decreased serum LH,maintained the secretion of FSH,and enhanced ER,PR,VEGFR2,and CD31 expression in decidual tissue.Conclusions Taxilli Herba demonstrated effective miscarriage-prevention effects in a rat model of threatened abortion.Its mechanism of action involves regulating the normal physiological function of the hypothalamic-pituitary-gonadal axis upstream of the uterus,and enhancing the expression of the downstream P/PR/VEGF/VEGFR2 and E/ER/VEGF/VEGFR2 pathways.
7.Interleukin-27 exerts a protective effect against psoriasis by inhibiting the secretion of interleukin-17A from T cells: a mechanistic study
Zhiyi LAN ; Zeyu CHEN ; Zihan ZHAO ; Xilin ZHANG ; Jun GU ; Yuling SHI
Chinese Journal of Dermatology 2025;58(11):1034-1041
Objective:To investigate the specific mechanisms underlying the protective effect of interleukin (IL) -27 in the pathogenesis of psoriasis.Methods:Five skin tissue samples from healthy individuals and 6 lesional skin samples from psoriasis patients were collected, and IL-27 expression was determined by immunohistochemical staining. Il27ra gene knockout (KO) mice were constructed. Psoriasis-like mouse models were established with topical imiquimod in 5 wild-type (WT) mice and 6 KO mice. Mouse skin lesions were evaluated using the modified Psoriasis Area and Severity Index (mPASI), and lesional skin tissues were collected for hematoxylin and eosin (HE) staining to observe changes in epidermal thickness. Single-cell suspensions were prepared with skin lesions and skin-draining lymph nodes of 4 WT mice and 3 KO mice, and changes in immune cells (including T cells, γδ T cells, and neutrophils) were analyzed using flow cytometry. Additionally, skin-draining lymph node cells were isolated from 9 normal WT mice, and IL-17A expression was stimulated using a T-cell receptor agonist (CD3/28 activating antibodies, αCD3/28) or cytokines (IL-23 + IL-1β), followed by the addition of IL-27; peripheral blood mononuclear cells (PBMCs) were isolated from 6 psoriasis patients, and IL-17A expression was stimulated using the T-cell receptor agonist, followed by the addition of IL-27; the effect of IL-27 on IL-17A expression in T cells was analyzed using flow cytometry and enzyme-linked immunosorbent assay (ELISA). Measurement data were compared between two groups using the t test. Results:Immunohistochemical staining revealed a significant reduction in IL-27 expression in psoriatic lesions (mean fluorescence intensity: 9.85 ± 3.07) compared with the normal skin (19.45 ± 2.51, t = 5.60, P < 0.001). Animal experiments demonstrated that the KO mice exhibited significantly aggravated psoriasis-like skin inflammation (mPASI: 4.00 ± 0.89) and significantly increased epidermal thickness (115.50 ± 7.69 μm) compared with the WT mice (mPASI: 2.80 ± 0.84, t = 2.28, P = 0.049; epidermal thickness: 92.26 ± 8.76 μm, t = 4.70, P = 0.001) ; compared with the WT mice, the KO mice showed significantly increased proportions of T cells (11.22% ± 2.76% vs. 7.08% ± 0.85%) and dermal γδ T cells (4.78% ± 0.39% vs. 2.78% ± 0.49%) among live cells in the lesions ( t = 2.91, 2.75, respectively, both P < 0.05), as well as significantly increased proportions of Th17, IL-17 + γδ T, Th22, and IL-22 + γδ T cells in the skin-draining lymph nodes (all P < 0.05), but no significant difference in the proportion of neutrophils in the lesions (WT: 13.57% ± 8.36%, KO: 14.43% ± 9.13%; t = 0.13, P = 0.902). Experiments with different stimuli showed that IL-27 significantly suppressed T-cell receptor agonist-induced IL-17A expression in murine γδ T cells (αCD3/28 group: 1.00 ± 0.11, αCD3/28 + IL-27 group: 0.76 ± 0.13; t = 3.54, P = 0.004), while there was no significant difference in IL-17A expression between cells induced by IL-23 + IL-1β with the IL-27 co-culture and those without ( t = 1.34, P > 0.05). ELISA showed that IL-27 significantly reduced the IL-17A concentration in the culture supernatant of draining lymph node cells stimulated by the T-cell receptor agonist (αCD3/28 group: 1 535.00 ± 97.76 pg/ml, αCD3/28 + IL-27 group: 1 030.00 ± 287.90 pg/ml, t = 3.29, P = 0.031), but did not reduce the IL-17A concentration induced by IL-23 + IL-1β ( t = 0.09, P > 0.05). Flow cytometry indicated that IL-27 significantly inhibited the T-cell receptor agonist-induced IL-17A expression in T cells from psoriasis patients (αCD3/28 group: 4.28 ± 3.25, αCD3/28 + IL-27 group: 3.04 ± 2.65, t = 4.46, P = 0.007) . Conclusion:IL-27 appeared to play a protective role in psoriasis by suppressing IL-17A secretion from T cells.
8.Research on the anti-abortive effect of Taxilli Herba aqueous decoction in rats
Yao LIU ; Yinyue SHI ; Ying CUI ; Lingling LI ; Zhiyi FENG
Acta Laboratorium Animalis Scientia Sinica 2025;33(6):790-801
Objective To investigate the effect and mechanism of Taxilli Herba decoction in preventing miscarriage in rats with threatened abortion.Methods Seventy-two SPF-grade SD rats were co-housed at a male-to-female ratio of 2∶1.Forty-eight pregnant rats were subsequently divided into a normal group,a threatened abortion model group,a positive control group,as well as Taxilli Herba decoction low/medium/high dose groups(n=8 rats per group).Rats in the positive control group received 3.02 mg/kg dydrogesterone intragastrically,and rats in the low-,medium-,and high-dose Taxilli Herba decoction groups received 2.5,5,and 10 g/kg Taxilli Herba decoction intragastrically,respectively.The normal and model groups received intragastric distilled water once a day for 10 consecutive days.On day 10 after administration of the corresponding treatment,rats in all groups except the normal group received intragastric administration of 3.75 mg/kg mifepristone suspension.The effects of Taxilli Herba on the vaginal bleeding rate and abortion rate were observed.Serum levels of follicle-stimulating hormone(FSH),luteinizing hormone(LH),estrogen(E),progesterone(P),vascular endothelial growth factor(VEGF),testosterone(T),and aromatase and E and P levels in the ovary in pregnant rats were detected by enzyme-linked immunosorbent assay.Expression levels of E receptor(ER),P receptor(PR),VEGF receptor 2(VEGFR2),and platelet endothelial cell adhesion molecule-1(CD31)in the uterine decidua in pregnant rats were detected by immunofluorescence staining,and semi-quantitative analysis was performed.Results Mifepristone significantly increased the vaginal bleeding rate and abortion rate in pregnant rats,but these were effectively reduced by treatment with Taxilli Herba water decoction.Taxilli Herba water decoction also increased serum E,P,and VEGF,and ovary levels of E and P(P<0.05).The treatment also decreased serum LH,maintained the secretion of FSH,and enhanced ER,PR,VEGFR2,and CD31 expression in decidual tissue.Conclusions Taxilli Herba demonstrated effective miscarriage-prevention effects in a rat model of threatened abortion.Its mechanism of action involves regulating the normal physiological function of the hypothalamic-pituitary-gonadal axis upstream of the uterus,and enhancing the expression of the downstream P/PR/VEGF/VEGFR2 and E/ER/VEGF/VEGFR2 pathways.
9.Analysis of factors influencing postoperative pathological upgrading in prostate cancer with target biopsy Gleason score 3 + 3 and development of a predictive model
Rongjie SHI ; Lai DONG ; Zhiyi SHEN ; Kaiyu ZHANG ; Chenglong ZHANG ; Yamin WANG ; Ruizhe ZHAO ; Shangqian WANG ; Gong CHENG ; Lixin HUA
Chinese Journal of Urology 2025;46(9):684-690
Objective:To explore the influencing factors for pathological upgrading in prostate cancer patients with a Gleason score of 3 + 3 undergoing targeted biopsy,and to establish a nomogram prediction model.Methods:A retrospective analysis was conducted on 191 patients with localized prostate cancer diagnosed with a Gleason score of 3 + 3 through targeted biopsies at the First Affiliated Hospital of Nanjing Medical University from January 2020 to June 2024. The age of the patients was 67(61,73)years,with prostate-specific antigen(PSA)level of 7.44(5.53,10.19)ng/ml,prostate volume of 35.64(26.59,48.97)ml,and PSA density(PSAD)of 0.20(0.14,0.31)ng/ml 2. Among them,61 cases(31.94%)had a Prostate Imaging Reporting and Data System(PI-RADS)score of 3,104 cases(54.45%)had a score of 4,and 26 cases(13.61%)had a score of 5. The diameter of the main lesion was 10.75(7.86,14.00)mm. The lesions were located in the peripheral zone in 78 cases(40.84%),the transition zone in 99 cases(51.83%),and the anterior fibromuscular stroma in 14 cases(7.33%). The lesions were found at the apex in 56 cases(29.32%),in the body in 120 cases(62.83%),and at the base in 15 cases(7.85%). MRI revealed only one lesion with a PI-RADS score ≥ 3 in 131 cases,two suspected lesions in 43 cases,three suspected lesions in 12 cases,and four suspected lesions in 5 cases. Systematic biopsy was positive in 121 cases(63.4%)and negative in 70 cases(36.6%). The lesions were confined to the left lobe in 63 cases(32.98%),right lobe in 68 cases(35.60%),and involved both lobes in 60 cases(31.41%). The interval between biopsy and surgery was 9.0(7.0,14.0)days. Univariate analyses were performed using Mann-Whitney U tests or χ2 tests,and multivariate logistic regression was used to identify independent predictors of pathological upgrading. A nomogram model was constructed based on these independent predictors. The model’s discriminative ability was assessed using the area under the receiver operating characteristic(ROC)curve(AUC),and internal validation of the model’s consistency was conducted using the bootstrap resampling method. Decision curve analysis(DCA)was performed to assess clinical utility. Results:Among the 191 cases,60(31.4%)had no pathological upgrading after surgery,while 131(68.6%)showed upgrading. Univariate analysis showed that the maximum diameter of the main lesion[9.0(6.0,13.2)mm vs. 11.0(8.4,14.0)mm],number of suspicious lesions on MRI[1.0(1.0,1.0)vs. 1.0(1.0,2.0)],number of positive systematic biopsy cores[1.0(0,2.0)vs. 1.0(0,3.0)],percentage of positive systematic biopsy cores[0.08(0,0.17)vs. 0.12(0,0.25)],number of positive targeted biopsy cores[2.0(1.0,3.0)vs. 3.0(1.0,4.0)],percentage of positive targeted biopsy cores[0.37(0.24,0.75)vs. 0.50(0.38,0.85)],level of the index lesion,location of the index lesion,and PI-RADS score were associated with pathological upgrading( P < 0.05). Multivariate logistic regression analysis showed that PI-RADS score 4( OR = 5.88,95% CI 2.41 - 14.35),number of suspicious lesions on MRI( OR = 4.15,95% CI 1.88 - 9.17),location of the index lesion in the transition zone( OR = 6.86,95% CI 2.81 - 16.73),and percentage of positive targeted biopsy cores( OR = 4.37,95% CI 1.38 - 14.90)were independent risk factors for pathological upgrading( P < 0.05). The nomogram model constructed using these predictors had an AUC of 0.845. Internal validation using the Bootstrap method yielded an AUC value of 0.812,indicating high predictive accuracy of the model. The calibration curve indicated good calibration. Decision curve analysis showed that the threshold range for net benefit in the model was between 12% - 100%. Conclusions:The PI-RADS score 4,the number of lesions with PI-RADS ≥ 3,the location of the main lesion in the transition zone,and the percentage of positive needles in targeted biopsy are independent risk factors for pathological upgrading from Gleason score 3 + 3. The nomogram model constructed from these factors demonstrates good predictive performance and provides a reference for clinical decision-making.
10.Effects of Huoxue Digui Decoction on Iron Accumulation and Ferroptosis in Renal Podocytes of Diabetic Nephropathy Mice Based on Nrf2/FPN1 Signaling Pathway
Zhiyi ZHANG ; Xueyi WANG ; Bing LI ; Jintao SHI ; Jiarui HAN
Chinese Journal of Information on Traditional Chinese Medicine 2024;31(12):105-111
Objective To observe the effects of Huoxue Digui Decoction on iron accumulation and ferroptosis in renal podocytes of diabetic nephropathy(DN)mice.Methods Totally 50 C57BL/6J mice were randomly divided into normal group(6 mice)and modeling group(44 mice).The DN model was established by streptozotocin injection.Mice conforming to DN model were randomly divided into model group(8 mice),and sulforaphane group,Huoxue Digui Decoction low-,medium-and high-dosage groups(6 mice for each group).The sulforaphane group was injected with sulforaphane intraperitoneally,while Huoxue Digui Decoction low-,medium-and high-dosage groups were orally administered with corresponding solution for 12 consecutive weeks.The fasting blood glucose,blood urea nitrogen,serum creatinine,24 h urinary albumin were detected,HE staining was used to observe the morphology of renal tissue,PAS staining was used to observe glycogen deposition in renal tissue,Masson staining was used to observe fibrosis in renal tissue;transmission electron microscopy was used to observe the ultrastructure of renal tissue,immunohistochemistry was used to detect the expressions of Podocin and Nephrin in renal tissue,Western blot was used to detect the protein expressions of glutathione peroxidase 4(GPX4),ACSL4,nuclear factor E2 related factor 2(Nrf2)and ferroportin 1(FPN1)in renal tissue,Prussian blue staining was used to observe the deposition of ferric ion in renal tissue.Results Compared with the normal group,the fasting blood glucose,blood urea nitrogen,serum creatinine and 24 h urinary albumin in model group significantly increased(P<0.01),with renal tissue capillary atrophy,increased glycogen deposition,and worsening fibrosis,the expressions of Podocin and Nephrin in renal tissue were down-regulated,while the expressions of GPX4,Nrf2 and FPN1 protein were significantly decreased(P<0.01),the expression of ACSL4 protein significantly increased(P<0.01),and the deposition of ferric ion in renal tissue increased.Compared with the model group,the fasting blood glucose,blood urea nitrogen,serum creatinine and 24 h urinary albumin in sulforaphane group and Huoxue Digui Decoction groups were reduced to different degrees(P<0.05,P<0.01),renal tissue pathological damage was reduced to varying degrees,glycogen deposition was reduced,and fibrosis was alleviated,the expressions of Podocin and Nephrin in renal tissue were up-regulated,while the expressions of GPX4,Nrf2 and FPN1 protein significantly increased(P<0.01),the expression of ACSL4 protein significantly decreased(P<0.05,P<0.01),and the deposition of ferric ion in renal tissue was reduced.Conclusion Huoxue Digui Decoction can alleviate renal pathological injury,reduce blood glucose and delay the progression of DN mice.The mechanism may be related to regulating the expressions of Nrf2 and FPN1,inhibiting iron accumulation and ferroptosis in renal podocytes of DN mice.


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