1.Erjingwan Alleviate Inflammatory Response and Apoptosis in Skeletal Muscle Cells of Sarcopenia via SIRT1/Nrf2/HO-1 Signaling Pathway
Long SHI ; Yang LI ; Hongyu YAN ; Tianle ZHOU ; Zhiwen ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(3):57-66
ObjectiveTo investigate the effects of the classical Chinese medicine compound prescription Erjingwan on the inflammatory response and apoptosis of skeletal muscle cells in a mouse model of sarcopenia and decipher the mechanism based on the silent information regulator 1 (SIRT1)/nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling pathway. MethodsForty C57/BL6 male mice were randomized into a control group, a model group, and groups with different doses of Erjingwan (8,16,32 g·kg-1). The mouse model of sarcopenia was established by D-gal-induced skeletal muscle senescence. The body weight and grip strength of mice treated with different doses of Erjingwan were examined to evaluate their physiological functions. Hematoxylin-eosin (HE) staining and Masson staining were used to observe the pathological changes and fibrosis in the skeletal muscle of mice. Enzyme-linked immunosorbent assay (ELISA) was adopted to determine the levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in the serum samples of mice, and biochemical tests were conducted to quantify the levels of superoxide dismutase (SOD), malondialdehyde (MDA), and glutathione (GSH) in the serum. The protein and mRNA levels of SIRT1, Nrf2, B-cell lymphoma (Bcl-2), and Bcl-2-associated X protein (Bax) were determined by Western blot and Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR), respectively. ResultsAfter 4 weeks of drug intervention, the model group exhibited significant reductions in body weight and grip strength (P0.01) compared with the control group. Compared with the model group, all doses of Erjingwan increased the body weight in mice at week 8 (P0.01) and grip strength from week 6 (P0.01). HE staining revealed clear muscle fiber structure in the control group, muscle fiber rupture and atrophy in the model group, and dose-dependent repair of muscle fiber structure in the Erjingwan groups. Masson staining showed minimal collagen fibers and mild fibrosis in the control group, collagen fiber proliferation and severe fibrosis in the model group, and collagen proliferation with dose-dependent inhibition of fibrosis in the Erjingwan groups. ELISA results showed that serum levels of TNF-α and IL-6 were elevated in the model group compared with those in the control group (P0.01). After intervention, the low-dose Erjingwan group exhibited a decreased TNF-α level (P0.05), while the medium and high-dose groups showed decreases in both TNF-α and IL-6 levels (P0.01). Biochemical assays revealed that the model group had decreased SOD and GSH levels (P0.01) and an increased MDA level (P0.01) compared with the control group. The medium and high-dose Erjingwan groups exhibited increases in SOD and GSH levels (P0.01) and decreases in MDA level (P0.01), compared with the model group. WB and Real-time PCR results showed that compared with the control group, the model group presented down-regulated protein and mRNA levels of SIRT1, Nrf2, HO-1, and Bcl-2 in the muscle tissue (P0.01) and up-regulated protein and mRNA levels of Bax (P0.01). Compared with the model group, Erjingwan at different doses up-regulated the protein levels of SIRT1, Nrf2, HO-1, and Bcl-2 (P0.01) and down-regulated the protein and mRNA levels of Bax (P0.01) in the muscle tissue. Low-dose Erjingwan elevated the mRNA levels of Nrf2 and HO-1 (P0.05, P0.01), and medium and high-dose Erjingwan up-regulated the mRNA levels of SIRT1, Nrf2, HO-1, and Bcl-2 (P0.01). ConclusionErjingwan reduced the content of inflammatory factors in skeletal muscle cells, improved the antioxidant capacity, and attenuated pathological changes and fibrosis in the muscle of the mouse model of sarcopenia by regulating the SIRT1/Nrf2/HO-1 pathway, inflammatory response, and apoptosis network.
2.Erjingwan Alleviate Inflammatory Response and Apoptosis in Skeletal Muscle Cells of Sarcopenia via SIRT1/Nrf2/HO-1 Signaling Pathway
Long SHI ; Yang LI ; Hongyu YAN ; Tianle ZHOU ; Zhiwen ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(3):57-66
ObjectiveTo investigate the effects of the classical Chinese medicine compound prescription Erjingwan on the inflammatory response and apoptosis of skeletal muscle cells in a mouse model of sarcopenia and decipher the mechanism based on the silent information regulator 1 (SIRT1)/nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling pathway. MethodsForty C57/BL6 male mice were randomized into a control group, a model group, and groups with different doses of Erjingwan (8,16,32 g·kg-1). The mouse model of sarcopenia was established by D-gal-induced skeletal muscle senescence. The body weight and grip strength of mice treated with different doses of Erjingwan were examined to evaluate their physiological functions. Hematoxylin-eosin (HE) staining and Masson staining were used to observe the pathological changes and fibrosis in the skeletal muscle of mice. Enzyme-linked immunosorbent assay (ELISA) was adopted to determine the levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in the serum samples of mice, and biochemical tests were conducted to quantify the levels of superoxide dismutase (SOD), malondialdehyde (MDA), and glutathione (GSH) in the serum. The protein and mRNA levels of SIRT1, Nrf2, B-cell lymphoma (Bcl-2), and Bcl-2-associated X protein (Bax) were determined by Western blot and Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR), respectively. ResultsAfter 4 weeks of drug intervention, the model group exhibited significant reductions in body weight and grip strength (P0.01) compared with the control group. Compared with the model group, all doses of Erjingwan increased the body weight in mice at week 8 (P0.01) and grip strength from week 6 (P0.01). HE staining revealed clear muscle fiber structure in the control group, muscle fiber rupture and atrophy in the model group, and dose-dependent repair of muscle fiber structure in the Erjingwan groups. Masson staining showed minimal collagen fibers and mild fibrosis in the control group, collagen fiber proliferation and severe fibrosis in the model group, and collagen proliferation with dose-dependent inhibition of fibrosis in the Erjingwan groups. ELISA results showed that serum levels of TNF-α and IL-6 were elevated in the model group compared with those in the control group (P0.01). After intervention, the low-dose Erjingwan group exhibited a decreased TNF-α level (P0.05), while the medium and high-dose groups showed decreases in both TNF-α and IL-6 levels (P0.01). Biochemical assays revealed that the model group had decreased SOD and GSH levels (P0.01) and an increased MDA level (P0.01) compared with the control group. The medium and high-dose Erjingwan groups exhibited increases in SOD and GSH levels (P0.01) and decreases in MDA level (P0.01), compared with the model group. WB and Real-time PCR results showed that compared with the control group, the model group presented down-regulated protein and mRNA levels of SIRT1, Nrf2, HO-1, and Bcl-2 in the muscle tissue (P0.01) and up-regulated protein and mRNA levels of Bax (P0.01). Compared with the model group, Erjingwan at different doses up-regulated the protein levels of SIRT1, Nrf2, HO-1, and Bcl-2 (P0.01) and down-regulated the protein and mRNA levels of Bax (P0.01) in the muscle tissue. Low-dose Erjingwan elevated the mRNA levels of Nrf2 and HO-1 (P0.05, P0.01), and medium and high-dose Erjingwan up-regulated the mRNA levels of SIRT1, Nrf2, HO-1, and Bcl-2 (P0.01). ConclusionErjingwan reduced the content of inflammatory factors in skeletal muscle cells, improved the antioxidant capacity, and attenuated pathological changes and fibrosis in the muscle of the mouse model of sarcopenia by regulating the SIRT1/Nrf2/HO-1 pathway, inflammatory response, and apoptosis network.
3.Mechanism by which KRT18 interacts with mRNA and long non-coding RNA to regulate intervertebral disc nucleus pulposus cell injury
Zhongyuan LIU ; Yang LI ; Zhiwen ZHANG
Chinese Journal of Tissue Engineering Research 2025;29(2):312-321
BACKGROUND:Differentially expressed RNA-binding proteins in the intervertebral disc plays a key role in intervertebral disc degeneration,and decreased levels of the RNA-binding protein KRT18 are associated with degenerative disc disease,but its specific role in the nucleus pulposus cells has not yet been fully determined. OBJECTIVE:To investigate the interaction of KRT18 with mRNA and long non-coding RNA on nucleus pulposus cells of the intervertebral disc and its mechanism. METHODS:Normal and degenerated nucleus pulposus cells were obtained from nucleus pulposus samples of patients undergoing interbody fusion for lumbar fracture or intervertebral disc degeneration.iRIP-seq,functional enrichment analysis,and DNA microarray analysis were performed to identify the mRNA and long non-coding RNA binding with KRT18.Subsequently,KRT18 was knocked down in nucleus pulposus cells based on the analysis results,and the expression levels of related genes were detected at the protein and RNA levels through protein immunoblotting and qRT-PCR,respectively. RESULTS AND CONCLUSION:Through iRIP-seq analysis,we identified abundant KRT18 binding sites within the GUAAUC and AGCCUC sequences,indicating that KRT18 may be involved in regulating RNA transcription,translation,stability or play a role in cell signaling pathways.It can stably bind to mature mRNA,among which highly expressed genes include CRLF1,IGFBP4,etc.At the same time,the peak genes of long non-coding RNA binding with it include SNHG25,SNHG12,NEAT1,USP32,EIF4A2 and CDH4.Most of these genes are involved in various biological processes such as apoptosis and inflammation,and can mediate related pathways of extracellular matrix metabolism.KRT18 can regulate their stability,transport,translation,splicing and other functions,thus affecting gene expression and cell function.We further verified through experiments the knockdown of KRT18 in nucleus pulposus cells,and found that the level of extracellular matrix metabolism was inhibited and unbalanced,resulting in intervertebral disc degeneration in vitro.This study investigated the regulatory mechanism of KRT18 from the perspective of its binding with mRNA and long non-coding RNA for the first time,and speculated the potential function of KRT18 in the pathogenesis of intervertebral disc degeneration,laying a foundation for future research on the key functions of KRT18.
4.Correlation studies of histopathological features,clinical prognosis,and genomic mutation profiles in non-small cell lung cancer
Lu HE ; Zhiwen LI ; Fanqing MENG ; Yipin WANG
Chinese Journal of Clinical and Experimental Pathology 2025;41(1):99-104
Lung cancer represents as one of the most prevalent malignant tumors globally,necessitating the urgent identification of additional biomarkers to facilitate precise stratified treatment and elevate its survival rates.Previous studies have focused on the correlation between the histopathological characteristics,driver gene mutations,and progno-sis of non-small cell lung cancer(NSCLC),with the aim of predicting the potential molecular background,treatment efficacy,and possible clinical outcomes of patients from the morphological perspective.This article aims to briefly sum-marize the advancements in emerging histopathological indicators of NSCLC,and discuss their implications for guiding the prognosis of this disease.
5.Mediating effect of intrinsic motivation of nurses between empowering leadership and job performance
Shujuan WEN ; Lili HOU ; Weihua WU ; Xiaomei JIANG ; Zhiwen ZHU ; Wenli ZHANG ; Lei YANG ; Siqi LI
Chinese Journal of Practical Nursing 2025;41(15):1168-1175
Objective:To explore the mediating effect of intrinsic motivation of nurses between empowering leadership and job performance, with the aim of providing a reference basis for managers to develop a scientific and effective intervention programme to improve nurses′ job performance.Methods:Convenience sampling method was used to select 1 213 clinical nurses from four tertiary general hospitals in Shandong Province, Henan Province, Yunnan Province, and Fujian Province from November to December 2023, and General Information Questionnaire, Empowering Leadership Scale, Intrinsic Motivation Scale, and Job Performance Scale were used to conduct a cross-sectional survey. AMOS26.0 software was used to test the mediating effect of intrinsic motivation of nurses between empowering leadership and job performance.Results:A total of 1 100 nurses completed the survey finally. Among them, there were 58 males and 1 042 females, 474 under 31 years old, 448 between 31-40 years old, and 178 over 40 years old.The total scores of the Empowering Leadership Scale, Intrinsic Motivation Scale, and Job Performance Scale were 49.44 ± 10.04, 82.35 ± 13.54 and 46.27 ± 6.20 in that order. Nurses' job performance were positive correlation with the empowered leadership and intrinsic motivation ( r=0.486, 0.703, both P<0.01), there was a positive correlation between nurse empowerment leadership and intrinsic motivation ( r=0.452, P<0.01). Nurses′ intrinsic motivation partially mediates the relationship between empowering leadership and job performance, accounting for 62.69% of the total effect. Conclusions:Intrinsic motivation of nurses is a mediating variable between empowered leadership and job performance. Nursing managers should focus on nurses' participation in autonomous decision-making to enhance nurses′ sense of competence and meaning at work, and mobilise their motivation to improve job performance.
6.Construction and usability evaluation of a clinical decision support system for frequency repositioning in ICU patients
Jiamin LI ; Haoqi WU ; Yufang HAO ; Zhiwen WANG ; Xinjuan WU
Chinese Journal of Nursing 2025;60(7):827-831
Objective This study aims to construct and evaluate a clinical decision support system for individualized frequency repositioning in ICU patients using big data and modern information technology,with the goal of improving ICU nursing quality.Methods From February to August 2023,a dedicated research team was established to construct a data model based on real-world data from 3,988 ICU patients,assessing the impact of different position change frequencies on the incidence of pressure injuries.Based on this model,a decision support system was designed and developed,incorporating modules for personalized patient characteristics input,data analysis and result queries,decision recording,and patient file management.From September to November 2023,ICU nurses at a tertiary hospital in Qingdao city was selected to use the system.A usability survey was conducted using the System Usability Scale(SUS)to evaluate the system's usability.Results The constructed decision support system can display the outcomes for patients under 7 different position change frequencies based on the input of personalized patient characteristics and the calculation results from the data model,providing precise decision support for nurses.A total of 85 nurses participated in the system usability evaluation,with the SUS score of 64.22±13.9.Conclusion The constructed individualized frequency of repositioning decision support system for ICU patients demonstrates good scientific validity and usability,providing clinical nurses with a valuable reference for implementing personalized position change frequencies for patients.
7.Mediating effect of intrinsic motivation of nurses between empowering leadership and job performance
Shujuan WEN ; Lili HOU ; Weihua WU ; Xiaomei JIANG ; Zhiwen ZHU ; Wenli ZHANG ; Lei YANG ; Siqi LI
Chinese Journal of Practical Nursing 2025;41(15):1168-1175
Objective:To explore the mediating effect of intrinsic motivation of nurses between empowering leadership and job performance, with the aim of providing a reference basis for managers to develop a scientific and effective intervention programme to improve nurses′ job performance.Methods:Convenience sampling method was used to select 1 213 clinical nurses from four tertiary general hospitals in Shandong Province, Henan Province, Yunnan Province, and Fujian Province from November to December 2023, and General Information Questionnaire, Empowering Leadership Scale, Intrinsic Motivation Scale, and Job Performance Scale were used to conduct a cross-sectional survey. AMOS26.0 software was used to test the mediating effect of intrinsic motivation of nurses between empowering leadership and job performance.Results:A total of 1 100 nurses completed the survey finally. Among them, there were 58 males and 1 042 females, 474 under 31 years old, 448 between 31-40 years old, and 178 over 40 years old.The total scores of the Empowering Leadership Scale, Intrinsic Motivation Scale, and Job Performance Scale were 49.44 ± 10.04, 82.35 ± 13.54 and 46.27 ± 6.20 in that order. Nurses' job performance were positive correlation with the empowered leadership and intrinsic motivation ( r=0.486, 0.703, both P<0.01), there was a positive correlation between nurse empowerment leadership and intrinsic motivation ( r=0.452, P<0.01). Nurses′ intrinsic motivation partially mediates the relationship between empowering leadership and job performance, accounting for 62.69% of the total effect. Conclusions:Intrinsic motivation of nurses is a mediating variable between empowered leadership and job performance. Nursing managers should focus on nurses' participation in autonomous decision-making to enhance nurses′ sense of competence and meaning at work, and mobilise their motivation to improve job performance.
8.A novel perspective on male testicular aging: Sertoli cell lysosomal dysfunction with intervention targets
Yunzhi LIN ; Yulin XIONG ; Zhiwen DENG ; Zheng LI ; Zhi ZHOU
Chinese Journal of Reproduction and Contraception 2025;45(11):1124-1130
Male reproductive aging is characterized by degenerative changes in the structure and function of the testes. Testicular aging involves alterations in various types of cells, among which lysosomal dysfunction in Sertoli cells is particularly critical. Recent studies have shown that abnormal lysosomal acidification leads to impaired phagosome degradation, which fails to maintain normal nutrient cycling and thereby exacerbates damage to the testicular microenvironment. In addition, endoplasmic reticulum stress, mitochondrial dysfunction, and epigenetic changes are also important factors contributing to reproductive aging. Therefore, molecular intervention strategies targeting lysosomal dysfunction, mitochondrial oxidative stress, and endoplasmic reticulum stress, such as the use of lysosomal activators like ML-SA1 and antioxidants, may offer new therapeutic directions for alleviating male reproductive aging. Future research should further explore the interactions between these mechanisms and potential intervention targets to improve reproductive health and quality of life in middle-aged and older men.
9.Association between the presence of peritumoral retraction clefts and clinicopatho-logical features and prognosis in esophageal squamous cell carcinoma
Ning ZHU ; Zhiwen LI ; Yuan FANG ; Li LI
Chinese Journal of Clinical and Experimental Pathology 2025;41(7):892-896,903
Purpose To investigate the clinicopathological significance of peritumoral retraction clefts(PRC)in esophageal squamous cell cancer(ESCC)and its correlation with prognosis.Methods 266 cases of esophageal squa-mous cell carcinoma were collected.Excluding the cases due to incomplete clinical data,cracks caused by the produc-tion process,and receiving preoperative adjuvant treatment,248 cases were finally counted.PRC was determined by the proportion of retraction clefts in the tumor volume of 10%.A retrospective analysis was conducted to explore the re-lationship between PRC and the clinicopathological features as well as prognosis of ESCC.Results Among 248 ESCC patients,114 cases had PRC,while 134 cases did not.Correlation analysis showed that PRC was closely related to his-tological grade,lymphatic invasion,lymph node metastasis,depth of tumor invasion and TNM stage of ESCC,and ES-CC patients with PRC were more likely to have lymphatic invasion and lymph node metastasis(P<0.05).In patients without lymphatic invasion,the probability of nodal metastasis in patients with PRC was higher than those without PRC,and the difference was statistically significant(P<0.001).Kaplan-Meier survival analysis showed that 5-year overall survival(P=0.001)and progression-free survival(P=0.002)in ESCC patients with PRC were significantly lower than those without PRC.Conclusion ESCC patients with PRC are more likely to have local invasiveness,lymphatic invasion and nodal metastasis,may predict the poor prognosis of ESCC patients.Patients with nodal metastasis are more common with PRC.
10.Relationship between systemic immune inflammation index and vitamin D in patients with type 2 diabetes based on restricted cubic spline
Min ZHAO ; Zhiwen LI ; Chenglong HUANG ; Xiaoju SHEN ; Guangming HUANG
The Journal of Practical Medicine 2025;41(15):2393-2397
Objective To investigate the correlation between plasma vitamin D levels and a novel inflam-matory marker,the systemic immune-inflammatory index(SII),in patients with type 2 diabetes.Methods This study adopted a cross-sectional design,in which patients diagnosed with type 2 diabetes who were admitted to the First Affiliated Hospital of Guangxi Medical University were enrolled as study participants.Data on demographic characteristics,medical history,physical examination findings,and laboratory test results were systematically collected.Participants were categorized into three groups based on their serum vitamin D levels:deficient,insuffi-cient,and sufficient.The relationship between vitamin D levels and the SII was evaluated using a multivariate linear regression model.Additionally,a restricted cubic spline model was employed to assess the nonlinear dose-response association between vitamin D levels and SII.Results This study enrolled a total of 5,716 patients with type 2 diabetes.A statistically significant difference in the SII was observed across groups with varying vitamin D levels(P<0.05),with the highest SII value found in the vitamin D-deficient group.Multivariate linear regression analysis revealed that,after adjusting for potential confounding factors including gender,age,season of blood collection,body mass index,hypertension,dyslipidemia,and chronic kidney disease,vitamin D levels were negatively associ-ated with SII(β=-2.68,95%CI:-3.56 to-1.81,P<0.001).Compared with the vitamin D-deficient group,the vitamin D-sufficient group exhibited significantly lower SII levels(β=-78.42,95%CI:-137.90 to-18.93,P=0.01).Furthermore,the restricted cubic spline model indicated a nonlinear dose-response relationship between vita-min D levels and SII(P<0.001).Conclusion There is a significant inverse correlation between plasma vitamin D levels and the SII in patients with type 2 diabetes.

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