1.Investigation of Mechanism of Simiaowan in Promoting Intestinal Uric Acid Excretion in Hyperuricemic Rats by Inhibiting Ferroptosis of Intestinal Epithelial Cells via SLC7A11/GPX4 Signaling Pathway
Zhongyou ZHANG ; Huilin FENG ; Lian DUAN ; Xuping FAN ; Shaoang DONG ; Lingchun WANG ; Bowen YE ; Hao DAI
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(18):151-161
ObjectiveTo investigate the mechanism by which Simiao Wan improve intestinal uric acid excretion in hyperuricemic (HUA) rats by inhibiting ferroptosis via the solute carrier family 7 member 11/glutathione peroxidase 4 (SLC7A11/GPX4) signaling pathway. MethodsForty-eight male SD rats were randomly assigned to a normal group, a model group, a low-dose Simiao Wan group (282.6 mg·kg-1), a high-dose Simiao Wan group (565.2 mg·kg-1), an etoricoxib group (5.4 mg·kg-1), and a ferroptosis inhibitor (Fer-1) group (2 mg·kg-1). Except for the normal group, rats in all other groups were intraperitoneally injected with potassium oxonate (100 mg·kg-1) combined with intragastric administration of hypoxanthine (500 mg·kg-1) to establish the HUA rat model. After 21 days, rats in each administration group received the corresponding dose of drug by gavage, rats in the Fer-1 group received intraperitoneal injection of Fer-1, and rats in the normal and model groups were given an equal volume of normal saline by gavage. After sampling, serum levels of uric acid (SUA), creatinine (Cr), and blood urea nitrogen (BUN) were measured using biochemical assays. The content of ferrous ion (Fe2+), reduced glutathione (GSH), and malondialdehyde (MDA), as well as superoxide dismutase (SOD) activity in ileal tissues were determined. Hematoxylin and eosin (HE) staining was performed to observe the histopathological changes in the ileum, and transmission electron microscopy was used to observe mitochondrial alterations in the ileal tissue. Immunohistochemistry (IHC) and Western blot were used to detect the protein expression levels of GPX4, ferritin heavy chain 1 (FTH1), acyl-CoA synthetase long-chain family member 4 (ACSL4), SLC7A11, and ATP-binding cassette transporter G2 (ABCG2) in ileal tissue. Real-time quantitative polymerase chain reaction (Real-time PCR) was used to determine the mRNA expression of GPX4, FTH1, ACSL4, SLC7A11, and ABCG2 in the ileal tissue. ResultsCompared with the normal group, the model group exhibited significantly elevated serum UA, Cr, and BUN levels (P<0.01), significantly increased content of MDA and Fe2+ in ileal tissue, and significantly decreased GSH content and SOD activity (P<0.01). HE staining showed extensive shedding of the ileal villous epithelium, disrupted and disorganized villous structure, and incomplete local tissue architecture. Transmission electron microscopy revealed reduced mitochondrial volume, decreased or even vanished cristae, indicating ultrastructural features characteristic of ferroptosis. Molecular and immunohistochemical results demonstrated that the protein and mRNA expression levels of GPX4, FTH1, SLC7A11, and ABCG2 were significantly downregulated, whereas those of ACSL4 were significantly upregulated (P<0.05, P<0.01). Compared with the model group, after intervention with Simiao Wan, the serum UA, Cr, and BUN levels significantly decreased in all dose groups (P<0.05,P<0.01), the MDA and Fe2+ content in ileal tissues were significantly reduced (P<0.01), and the GSH content and SOD activity significantly increased (P<0.01). HE staining showed that the shedding of ileal villous epithelium was markedly alleviated, the villous structure became relatively intact and regularly arranged, and local tissue damage was obviously improved. Transmission electron microscopy showed attenuated mitochondrial damage, improvement in mitochondrial shrinkage, and partial restoration of mitochondrial cristae. Molecular and immunohistochemical results showed that Simiao Wan upregulated GPX4, FTH1, SLC7A11, and ABCG2, and downregulated ACSL4 in a dose-dependent manner. In the high‑dose group, all indices improved significantly (P<0.05,P<0.01), whereas in the low‑dose group, only improving trends were observed for FTH1, SLC7A11 mRNA, and ABCG2 protein. ConclusionSimiao Wan may inhibit ferroptosis of ileal epithelial cells by regulating the SLC7A11/GPX4 signaling pathway, and upregulate the expression of the uric acid transporter ABCG2, thereby promoting intestinal uric acid excretion and improving HUA.
2.The analysis of prognosis factors of tongue squamous cell carcinoma
Kun WU ; Bowen DAI ; Hanjiang WU
Journal of Practical Stomatology 2025;41(6):798-801
Objective:To analyze the prognostic factors of tongue squamous cell carcinoma(TSCC)and provide a clinical refer-ence for the treatment of TSCC.Methods:329 patients underwent radical resection of TSCC primary tumor and neck dissection were included in this study.Results:The overall 5-year survival rate was 73.01%and the local control rate was 84.74%.Cox multivari-ate analysis showed that age(P=0.045 1),histological grade(P<0.000 1)and clinical stage(P=0.004 9)were closely related to the 5-year overall survival rate of the patients with TSCC.Multivariate linear regression analysis showed that histopathological grade(P=0.000 3),T stage(P=0.009 7)and lymph node metastasis(P=0.040 6)was closely related to local disease control in the patients.Conclusion:Age,histological grade and clinical stage are important prognostic factors,the histological grade,T stage and lymph node metastasis are closely related to local disease control in patients with TSCC.
3.The effects of resveratrol on the level of autophagy in the spleen of mice with OSAHS
Liru ZHAO ; Guanzhou HOU ; Bowen DAI ; Xiaolei GE ; Xiuge GU ; Yang LIU ; Linna WANG ; Xinyu XIE ; Jiaqi MAO
Journal of Practical Stomatology 2025;41(2):200-205
Objective:To study the effects of hypoxia on the autophagy level in the spleen of mice with OSAHS.Methods:Mouse OSAHS hypoxia model was established in 24 C57BL/6 mice and the mice were divided into 3 groups:normoxic group,hypoxic group and resveratrol group(n=8).Real time PCR,Western blot and immunohistochemical staining(IHC)were used to detect the mRNA and protein expression of autophagy related proteins microtube associated protein 1 light chain 3 B(LC3B),myosin-like BCL2 inteacting protein(Beclin1)and autophagy related gene 5(ATG5)in mouse spleen respectively.Results:The mRNA expres-sion of LC3B,Beclin1,and ATG5 in the hypoxic group was lower than that in the normoxic group(P<0.01,P<0.01,P<0.001),resveratrol upregulated the expression levels of LC3B and ATG5 mRNA in the hypoxic group(P<0.05,P<0.001),but did not up-regulate the expression of Beclin1(P>0.05).The protein expression levels of LC3B,Beclin1 and ATG5 in the hypoxic group were lower than that in the normoxic group(P<0.05,P<0.05,P<0.01).Resveratrol upregulated the expression levels of LC3B and ATG5 in the hypoxic group(P<0.05,P<0.01),but did not upregulated the expression of Beclin1(P>0.05).IHC test showed that the expression level of LC3B,Beclin1 and ATG5 in the hypoxic group was lower than that in the normoxic group(P<0.01,P<0.01,P<0.001).Resveratrol increased the expression level of LC3B and ATG5 in the hypoxic group(P<0.05,P<0.01),but did not upregulate the expression of Beclin1(P>0.05).Conclusion:Hypoxia may inhibite the autophagy level of spleen in mice.Resvera-trol derivatives increases the autophagy level of mice under hypoxia condition,but has no significant effect on Beclin1 expression.
4.Osteogenic ability and autophagy level between normal and inflammatory periodontal ligament stem cells
Jiaqi MAO ; Liru ZHAO ; Dongru YANG ; Yongqing HU ; Bowen DAI ; Shujuan LI
Chinese Journal of Tissue Engineering Research 2025;29(1):74-79
BACKGROUND:Inflammation affects the osteogenic differentiation of periodontal ligament stem cells,and the osteogenic ability and autophagy level of periodontal ligament stem cells are closely related.However,there are no relevant reports on whether inflammation affects the osteogenic ability and autophagy level of periodontal ligament stem cells at different stages of osteogenic differentiation. OBJECTIVE:To explore alkaline phosphatase expression and autophagy periodontal ligament stem cells levels in periodontitis and normal conditions. METHODS:Periodontal ligament stem cells from normal and periodontitis patients were isolated and cultured,and underwent Vimentin,pan-CK,and Stro-1 fluorescence staining.At 3,7,and 14 days of osteogenic differentiation,western blot assay was used to detect the protein expression levels of alkaline phosphatase,LC3B,Beclin1,and ATG5 in normal and inflammatory periodontal ligament stem cells.The mRNA expression levels of alkaline phosphatase,bone sialoprotein,osteocalcin,Runx2,LC3B,Beclin1,and ATG5 were detected by real-time PCR. RESULTS AND CONCLUSION:(1)Stro-1 was positive,Vimentin was positive,and pan CK was negative in periodontal ligament stem cells.(2)At 3,7,and 14 days after osteogenic differentiation,compared with normal periodontal ligament stem cells,the mineralization nodules formed by periodontal ligament stem cells from inflammatory sources were significantly reduced(P<0.01);the expression of alkaline phosphatase protein and mRNA was significantly lower(P<0.05);the mRNA expression levels of bone sialoprotein,osteocalcin,and Runx2 were significantly decreased(P<0.05).(3)At 7 and 14 days after osteogenic differentiation,compared with normal periodontal ligament stem cells,the expression levels of ATG5,LC3B,and Beclin1 proteins and mRNA of periodontal ligament stem cells were downregulated(P<0.05).These findings suggest that inflammation reduces the activity of periodontal ligament stem cells in mineralizing nodule formation and the expression of alkaline phosphatase and weakens the autophagy potential of periodontal ligament stem cells at 7 and 14 days after osteogenic differentiation.
5.The effects of resveratrol on the level of autophagy in the spleen of mice with OSAHS
Liru ZHAO ; Guanzhou HOU ; Bowen DAI ; Xiaolei GE ; Xiuge GU ; Yang LIU ; Linna WANG ; Xinyu XIE ; Jiaqi MAO
Journal of Practical Stomatology 2025;41(2):200-205
Objective:To study the effects of hypoxia on the autophagy level in the spleen of mice with OSAHS.Methods:Mouse OSAHS hypoxia model was established in 24 C57BL/6 mice and the mice were divided into 3 groups:normoxic group,hypoxic group and resveratrol group(n=8).Real time PCR,Western blot and immunohistochemical staining(IHC)were used to detect the mRNA and protein expression of autophagy related proteins microtube associated protein 1 light chain 3 B(LC3B),myosin-like BCL2 inteacting protein(Beclin1)and autophagy related gene 5(ATG5)in mouse spleen respectively.Results:The mRNA expres-sion of LC3B,Beclin1,and ATG5 in the hypoxic group was lower than that in the normoxic group(P<0.01,P<0.01,P<0.001),resveratrol upregulated the expression levels of LC3B and ATG5 mRNA in the hypoxic group(P<0.05,P<0.001),but did not up-regulate the expression of Beclin1(P>0.05).The protein expression levels of LC3B,Beclin1 and ATG5 in the hypoxic group were lower than that in the normoxic group(P<0.05,P<0.05,P<0.01).Resveratrol upregulated the expression levels of LC3B and ATG5 in the hypoxic group(P<0.05,P<0.01),but did not upregulated the expression of Beclin1(P>0.05).IHC test showed that the expression level of LC3B,Beclin1 and ATG5 in the hypoxic group was lower than that in the normoxic group(P<0.01,P<0.01,P<0.001).Resveratrol increased the expression level of LC3B and ATG5 in the hypoxic group(P<0.05,P<0.01),but did not upregulate the expression of Beclin1(P>0.05).Conclusion:Hypoxia may inhibite the autophagy level of spleen in mice.Resvera-trol derivatives increases the autophagy level of mice under hypoxia condition,but has no significant effect on Beclin1 expression.
6.Development and psychometric evaluation of the Nurse Parenting Stress Scale
Haixiao YU ; Yueguang DAI ; Bowen LI ; Xiujuan CHEN ; Shengjie JIA ; Zhaozhao XU ; Shuxiang ZHANG ; Xiaomin LIU
Chinese Journal of Modern Nursing 2025;31(35):4803-4808
Objective:To develop the Nurse Parenting Stress Scale and evaluate its reliability and validity.Methods:Based on Abidin's Parenting Stress Theory, scale items were generated through literature review and semi-structured interviews. The initial version was constructed via Delphi expert consultation. Using a convenience sampling method, nurses from six hospitals in Shandong Province were surveyed between August and October 2024. The first survey collected 314 questionnaires (308 valid, effective recovery rate 98.1%) for item analysis and exploratory factor analysis (EFA). The second survey collected 458 questionnaires (447 valid, effective recovery rate 97.6%) for confirmatory factor analysis (CFA) .Results:The Nurse Parenting Stress Scale consists of 4 dimensions and 31 items. The Cronbach's α coefficient of the total scale was 0.951, split-half reliability was 0.782, and test-retest reliability was 0.926. EFA extracted four common factors explaining 70.241% of the cumulative variance. CFA demonstrated a good model fit. The item-level content validity index ( I- CVI) ranged from 0.889 to 1.000, the scale-level universal agreement content validity index ( S- CVI/ UA) was 0.903, and the scale-level average content validity index ( S- CVI/ Ave) was 0.989. Conclusions:The Nurse Parenting Stress Scale shows strong reliability and validity and can serve as an effective tool for assessing parenting stress among nurses.
7.Development and psychometric evaluation of the Nurse Parenting Stress Scale
Haixiao YU ; Yueguang DAI ; Bowen LI ; Xiujuan CHEN ; Shengjie JIA ; Zhaozhao XU ; Shuxiang ZHANG ; Xiaomin LIU
Chinese Journal of Modern Nursing 2025;31(35):4803-4808
Objective:To develop the Nurse Parenting Stress Scale and evaluate its reliability and validity.Methods:Based on Abidin's Parenting Stress Theory, scale items were generated through literature review and semi-structured interviews. The initial version was constructed via Delphi expert consultation. Using a convenience sampling method, nurses from six hospitals in Shandong Province were surveyed between August and October 2024. The first survey collected 314 questionnaires (308 valid, effective recovery rate 98.1%) for item analysis and exploratory factor analysis (EFA). The second survey collected 458 questionnaires (447 valid, effective recovery rate 97.6%) for confirmatory factor analysis (CFA) .Results:The Nurse Parenting Stress Scale consists of 4 dimensions and 31 items. The Cronbach's α coefficient of the total scale was 0.951, split-half reliability was 0.782, and test-retest reliability was 0.926. EFA extracted four common factors explaining 70.241% of the cumulative variance. CFA demonstrated a good model fit. The item-level content validity index ( I- CVI) ranged from 0.889 to 1.000, the scale-level universal agreement content validity index ( S- CVI/ UA) was 0.903, and the scale-level average content validity index ( S- CVI/ Ave) was 0.989. Conclusions:The Nurse Parenting Stress Scale shows strong reliability and validity and can serve as an effective tool for assessing parenting stress among nurses.
8.The analysis of prognosis factors of tongue squamous cell carcinoma
Kun WU ; Bowen DAI ; Hanjiang WU
Journal of Practical Stomatology 2025;41(6):798-801
Objective:To analyze the prognostic factors of tongue squamous cell carcinoma(TSCC)and provide a clinical refer-ence for the treatment of TSCC.Methods:329 patients underwent radical resection of TSCC primary tumor and neck dissection were included in this study.Results:The overall 5-year survival rate was 73.01%and the local control rate was 84.74%.Cox multivari-ate analysis showed that age(P=0.045 1),histological grade(P<0.000 1)and clinical stage(P=0.004 9)were closely related to the 5-year overall survival rate of the patients with TSCC.Multivariate linear regression analysis showed that histopathological grade(P=0.000 3),T stage(P=0.009 7)and lymph node metastasis(P=0.040 6)was closely related to local disease control in the patients.Conclusion:Age,histological grade and clinical stage are important prognostic factors,the histological grade,T stage and lymph node metastasis are closely related to local disease control in patients with TSCC.
9.Upregulated SKP2 Empowers Epidermal Proliferation Through Downregulation of P27 Kip1
Lipeng TANG ; Bowen ZHANG ; Guanzhuo LI ; Xinmin QIU ; Zixin DAI ; Hongying LIU ; Ying ZHU ; Bing FENG ; Zuqing SU ; Wenhui HAN ; Huilin HUANG ; Qiuping LI ; Zihao ZHANG ; Maojie WANG ; Huazhen LIU ; Yuchao CHEN ; Yanmei ZHANG ; Dinghong WU ; Xirun ZHENG ; Taohua LIU ; Jie ZHAO ; Chutian LI ; Guangjuan ZHENG
Annals of Dermatology 2024;36(5):282-291
Background:
Excessive growth of keratinocytes is the critical event in the etiology of psoriasis.However, the underlying molecular mechanism of psoriatic keratinocyte hyperproliferation is still unclear.
Objective:
This study aimed to figure out the potential contributory role of S-phase kinase-associated protein 2 (SKP2) in promoting the hyperproliferation of keratinocytes in psoriasis.
Methods:
We analyzed microarray data (GSE41662) to investigate the gene expression of SKP2in psoriatic lesion skins compared with their adjacent non-lesional skin. Then, we further confirmed the mRNA and protein expression of SKP2 in human psoriatic skin tissues, imiquimod (IMQ)-induced psoriatic mice back skins and tumor necrosis factor α (TNF-α), interleukin (IL)-17A and IL-6-stimulated keratinocytes by using real-time quantitative polymerase chain reaction and western blot (WB). Furthermore, we explored the potential pathogenic role and its underlying cellular mechanism of SKP2 in promoting keratinocytes hyperproliferation through 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, cell cycle detection, 5-ethynyl-2′-deoxyuridine staining and WB. Finally, we determined whether inhibition of SKP2 can effectively alleviate the keratinocytes hyperproliferation in vivo.
Results:
We identified that SKP2 is aberrantly upregulated in the psoriatic lesion skin and cytokines-stimulated keratinocytes. Moreover, upregulated SKP2 augments cytokines-induced keratinocytes hyperproliferation. Mechanistically, enhanced SKP2 increased the S phase ratio through inhibiting Cyclin-Dependent Kinase Inhibitor p27 (P27 Kip1) expression. Correspondingly, suppression of SKP2 with SMIP004 can significantly ease the epidermis hyperplasia in vivo.
Conclusion
Our results suggest that elevated SKP2 can empower keratinocytes proliferation and psoriasis-like epidermis hyperplasia via downregulation of P27 Kip1. Therefore, targeting SKP2-P27 Kip1 axis might be a promising therapeutic strategy for the treatment of psoriasis in future.
10.The analysis of unconventional lymph node metastasis in tongue squamous cell carcinoma
Kun WU ; Bowen DAI ; Hanjiang WU
Chinese Journal of Otorhinolaryngology Head and Neck Surgery 2024;59(3):227-232
Objective:To analyze the characteristics of cervical lymph node metastasis in tongue squamous cell carcinoma (TSCC).Methods:A retrospective study was conducted. A total of 329 patients with TSCC who underwent en bloc resection of primary tumor and neck dissection in the Second Xiangya Hospital of Central South University from June 2010 to March 2018 were included. There were 283 males and 46 females, aged from 26 to 80 years. All patients underwent the modified neck dissection. The main difference between the modified neck dissection and the traditional neck dissection lay in the managements of unconventional lymph nodes. The lymphatic adipose tissues adjacent to the superior thyroid artery, the base of facial artery and the branches of external carotid artery were thoroughly dissected. The primary tumor as well as lingual artery, tissues along the lingual artery and lymph nodes in the mouth floor were resected. χ 2 test was used for comparison of count data, and linear regression model was used for multivariate analysis. Results:Cervical lymph node metastases were found in 136 patients (41.3%). Among 142 patients (T1-2cN0) with supraomohyoid neck dissection, 22 patients had pathologically occult lymph node metastases (15.5%), with a 5-year overall survival rate of 90.2%, which was similar to the 5-year overall survival rate of 92.1% in 120 patients without lymph node metastasis (χ 2=0.156, P=0.693). Multivariate linear regression analysis showed that T stage, clinical stage and unconventional lymph node metastasis were important factors for cervical lymph node metastasis in tongue cancer patients ( P<0.05). Unconventional lymph node metastases occurred in 30 patients (9.1%), including the metastases of lymph nodes in the floor of mouth (3.0%), the lingual artery (2.4%), the base of the external maxillary artery (2.1%), the superior thyroid artery (0.9%), and the external carotid artery (0.6%). There were significant differences in the unconventional lymph node metastasis rates between patients with negative and positive conventional lymph node metastases [4.9%(10/203) vs. 15.9%(20/126), χ 2=11.242, P=0.001] and also between patients with depth of invasion ≤5 mm, 5 mm

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