1.Effect of Epimedium brevicornu Ethanol Extract on Aging of Castrated Rats by Intervening in Mesenchymal Adipose-derived Stem Cells
Zuyu MENG ; Haiquan LIU ; Shaozi LIN ; Mei WANG ; Yiyao ZHANG ; Fang LIU ; Menghan LI ; Hongling CHEN ; Jiajia QIN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(1):174-181
ObjectiveTo explore the mechanism by which the ethanol extract of Epimedium brevicornu (EEBM) intervenes in mesenchymal adipose-derived stem cells (ADSCs) to delay aging in castrated rats. MethodsForty-five 3-month-old SPF female SD rats were ovariectomized and randomly divided into model group, ADSCs treatment group, and ADSCs groups treated with low, medium, and high concentrations of EEBM (1, 50, 100 μg·L-1), referred to as the AE low, medium, and high concentration groups, with 9 rats in each group. After tail vein injection of 200 μL of the corresponding stem cell suspension, aging-related indicators including cyclin-dependent kinase inhibitor (p21), tumor suppressor gene (p53), interleukin-6 (IL-6), interleukin-8 (IL-8), superoxide dismutase (SOD), malondialdehyde (MDA), B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X protein (Bax), cysteine-aspartic acid protease-3 (Caspase-3), and lipofuscin were measured using enzyme-linked immunosorbent assay (ELISA) and Western blot. ResultsCompared with the model group, the IL-6 content in the AE low, medium, and high concentration groups was significantly decreased (P<0.05). Lipofuscin, MDA, and IL-8 levels in the ADSCs treatment group and AE low, medium, and high concentration groups were significantly reduced (P<0.01), while SOD content was significantly increased (P<0.05, P<0.01). Compared with the ADSCs treatment group, lipofuscin and IL-8 levels in the AE low, medium, and high concentration groups were significantly reduced (P<0.05, P<0.01). The MDA content was significantly decreased in the AE medium concentration group (P<0.01). Compared with the model group, protein levels of p21, p53, Bax, and Caspase-3 in the ADSCs treatment group and AE low, medium, and high concentration groups were significantly reduced (P<0.05, P<0.01), while the Bcl-2 protein level was significantly increased (P<0.01). Compared with the ADSCs treatment group, protein levels of p21, p53, Bax, and Caspase-3 in the AE low, medium, and high concentration groups were significantly reduced (P<0.05, P<0.01), and the Bcl-2 protein level in the AE low concentration group was significantly increased (P<0.01). ConclusionThe results of this experiment show that EEBM-treated ADSCs or ADSCs may delay aging in castrated rats by inhibiting cell apoptosis, reducing cell cycle inhibitors and pro-inflammatory factors, enhancing antioxidant capacity, and reducing oxidative reactions. Moreover, EEBM-treated ADSCs demonstrate stronger anti-aging effects than ADSCs alone. This study provides experimental evidence supporting the clinical use of EEBM to intervene in ADSCs and delay aging.
2.The role of CYP2E1 in trichloroethylene-induced skin sensitization and liver damage in guinea pigs
Lijuan WU ; Xiangrong SONG ; Fengrong LU ; Hongling LI ; Jiaheng HE ; Xiao ZHANG ; Hailan WANG
China Occupational Medicine 2025;52(3):249-256
Objective To investigate the role of cytochrome P450 2E1 (CYP2E1) in trichloroethylene (TCE)-induced skin sensitization and liver damage in guinea pigs, using diallyl sulfide (DAS), a CYP2E1 inhibitor, as an intervention. Methods Specific pathogen-free female guinea pigs were randomly divided into blank control group, solvent control group, positive control (2,4-dinitrochlorobenzene) group, TCE-exposure group, and DAS-intervention group. Skin sensitization experiments were conducted using the guinea pig TCE maximal dose-skin sensitization test. Urinary trichloroacetic acid levels were determined following TCE induction and challenge. At 48 hours after the final challenge, serum liver function markers and inflammatory cytokines levels were detected. Histopathological examination on skin and liver tissues was performed, and hepatic CYP2E1 protein expression and oxidative stress indicators were assessed. Results The sensitization rates of guinea pigs were 100.0%, 75.0%, and 33.3% in the positive control, TCE-exposure, and DAS-intervention groups, respectively, while the blank control and solvent control groups were both 0.0%. Compared with the guinea pigs in TCE-exposure group, those in the DAS-intervention group had lower urinary trichloroacetic acid levels at intradermal induction, local induction, first challenge, and 24 hours after the final challenge time point (all P<0.05). Histopathology of guinea pigs showed dermal inflammatory infiltration and basal keratinocyte necrosis in the TCE-exposure group, whereas only mild dermal inflammation was observed in the DAS-intervention group. The guinea pigs in TCE-exposure group exhibited diffuse hepatocellular necrosis, while hepatic damage in the DAS-intervention group was alleviated, characterized by only mild hepatocellular steatosis and hepatocyte swelling around the central vein. The skin sensitization rate of guinea pigs in the TCE-exposure group increased (all P<0.01), the serum alanine aminotransferase (ALT )activity, the levels of interleukin (IL)-2, IL-17, and tumor necrosis factor-α (TNF- α) increased (all P<0.05), the relative expression of CYP2E1 protein, the activity of superoxide dismutase (SOD), and the level of malondialdehyde in liver tissue increased (all P<0.05), while the activity of catalase decreased (P<0.05), compared with the blank control and solvent control groups. The serum ALT activity and the levels of IL-2, IL-17, and TNF-α of guinea pigs in DAS-intervention group reduced (all P<0.05), as well as CYP2E1 protein expression, SOD activity, and malondialdehyde level in liver tissue reduced (all P<0.05), compared with the TCE-exposure group. Conclusion TCE can induce hepatic CYP2E1 expression, thereby promoting oxidative stress and inflammatory responses, which contributes to skin sensitization and liver damage. DAS alleviates TCE-induced toxic effects on skin and liver by inhibiting CYP2E1 expression.
3.Intervention effect and mechanism of breviscapine on hepatic fibrosis in rats
Dandan WEI ; Shanshan LI ; Minghao ZHANG ; Yurun WEI ; Hongling WANG ; Shuangshuang CHAI ; Jingjing YIN ; Min ZHANG ; Han ZHAO ; Zongyao WU ; Kuicheng ZHU ; Qingbo WANG
China Pharmacy 2024;35(6):671-677
OBJECTIVE To investigate the intervention effect and potential mechanism of breviscapine on hepatic fibrosis (HF) in rats based on the transforming growth factor-β(1 TGF-β1)/Smad2/extracellular signal-regulated protein kinase 1(ERK1) and Kelch-like epichlorohydrin-associated protein 1(Keap1)/nuclear factor-erythroid 2-related factor 2(Nrf2)/heme oxygenase-1(HO-1) pathways. METHODS Totally 60 rats were randomly divided into normal control group, model group, breviscapine low-dose, medium-dose and high-dose groups (5.4, 10.8, 21.6 mg/kg), and colchicine group (positive control, 0.45 mg/kg), with 10 rats in each group, half male and half female. Except for the normal control group, HF model of the other groups was induced by carbon tetrachloride. Subsequently, each drug group was given corresponding medicine by gavage once a day for 28 days. The liver appearance of rats in each group was observed and their liver coefficients were calculated. The levels of alanineaminotransferase (ALT) and aspartate aminotransferase (AST)in serum, those of ALT, AST, superoxide dismutase (SOD),malondialdehyde (MDA) and glutathione peroxidase (GSH- Px) in liver tissue were detected. The liver tissue inflammatory and fibrotic changes were observed. The protein and mRNA expressions of TGF-β1, Smad2, ERK1, Nrf2, Keap1 and HO-in liver tissue were detected. RESULTS Compared with the normal control group, the model group showed large areas of white nodular lesions in the liver, obvious inflammatory cell infiltration and collagen fiber deposition. The body weight, the levels of SOD and GSH-Px in liver tissue, the protein and mRNA expressions of Nrf2 and HO-1 were significantly lowered in the model group (P<0.05); the liver coefficient, the percentage of Masson staining positive area, ALT and AST levels of serum and liver tissue, MDA level of liver tissue, the protein and mRNA expressions of TGF-β1, Smad2, ERK1 and Keap1 were significantly increased (P<0.05). Compared with the model group, the liver lesions of rats in each drug group were improved, and the above quantitative indexes were generally reversed (P<0.05). CONCLUSIONS Breviscapine has a good intervention effect on HF rats, which may be related to inhibiting TGF-β1/Smad2/ERK1 pathway for anti-fibrosis and regulating Keap1/Nrf2/HO-1 pathway to inhibit oxidative stress.
4.Characterization of Metabolic Reprogramming in Head and Neck Squamous Cell Carcinoma and Application Prospects for Targeted Therapy
Ruilin WANG ; Yuxiu MA ; Xuelin LIU ; Qi ZHANG ; Guoyin WANG ; Hongling LI
Cancer Research on Prevention and Treatment 2024;51(12):1046-1050
Head and neck squamous cell carcinoma (HNSCC) is the seventh most common malignant tumor in the world, with a 5-year survival rate of only about 50%. Thus, discovering more effective diagnostic and therapeutic approaches is an urgent need. The metabolic reprogramming of tumor cells is a key feature in the development of HNSCC, which widely exhibits alterations in glycolytic metabolism, lipid metabolism, and amino acid metabolism compared with normal cells. Metabolic reprogramming affects the energy supply and biosynthesis of tumor cells. It also participates in the regulation of the tumor microenvironment and promotes key biological processes such as proliferation, invasion, and metastasis of HNSCC. With the progressive understanding of the complexity of tumor biology, targeted-therapy strategies against metabolic reprogramming in HNSCC are emerging as a promising therapeutic approach. These metabolically targeted therapies have performed well in preclinical studies, but their clinical application requires further validation. In the future, we need to deeply explore the more complex features of metabolic reprogramming and its biological significance in HNSCC, with the aim of discovering more effective diagnostic and therapeutic targets, as well as providing new strategies to improve the prognosis of HNSCC patients.
5.The Correlation between Twist2 Expression and Vascular Infiltration and Prog-nosis in Ovarian Cancer
Jingjing JIANG ; Hongling ZHANG ; Fangfang FU ; Tian WANG
Journal of Practical Obstetrics and Gynecology 2024;40(5):369-373
Objective:To analyze the relationship between Twist2 and the prognosis and vascular infiltration of ovarian cancer patients,and to explore the role and mechanism of Twist2 in vascular infiltration of ovarian cancer.Methods:KM plotter was used to explore the correaltion between Twist2 mRNA expression and overall survival(OS),progression free survival(PFS)and post progression survival(PPS)in ovarian cancer.To analyze the cor-relation between Twist2 and vascular infiltration in ovarian cancer using the cancer genomics database cBioPor-tal.In vitro experiment:Transwell method was employed to determine the role of Twist2 in the invasion and migra-tion abilities of ovarian cancer cell CAOV3[blank group,negative control group(siNC group),siTwist2 group].Uti-lizing Realtime-PCR and Western blot to clarify the changes in Twist2 and VEGFC expression in CAOV3 cells af-ter downregulating Twist2 expression at the RNA and protein levels,respectively.Results:①Online data analysis of KM plotter showed that the ovarian cancer patients with high expression of Twist2 were associated with poor prognosis,with OS(HR 1.24,95%Cl 1.01-1.52),PFS(HR 1.39,95%CI 1.14-1.70)and PPS(HR 1.37,95%CI 1.08-1.74)all showing statistical significance(P<0.05).CBioportal analysis showed that Twist2 mRNA expression was positively correlated with vascular infiltration(r=0.93,P=0.001)and lymphatic infiltration(r=0.89,P=0.009)in ovarian cancer.②Compared with the blank group and siNC group,in vitro experiment Tran-swell assay showed that the invasion and migration ability of ovarian cancer cells in siTwist2 group was significant-ly reduced(P<0.05).In mRNA and protein level,Realtime-PCR and Western blot showed that compared with the blank group and siNC group,the expression of Twist2,as well as VEGFC,were significantly reduced in the siTwist2 group(P<0.05).Conclusions:The expression of Twist2 in ovarian cancer is closely related to tumor prognosis and vascular infiltration.After downregulating Twist2,the number of cells that migrate and invade is sig-nificantly reduced,and the expression of VEGFC is reduced.Twist2 can induce migration and invasion of ovarian cancer cells through VEGFC,which may be one of the indicators for prognosis evaluate and targeted therapy of ovarian cancer in future.
6.Construction of the quality evaluation scale of specification of management for humanistic caring in outpatients and its reliability and validity testing
Lixia YUE ; Na CUI ; Xu CHE ; Heng ZHANG ; Hongxia WANG ; Shujie GUO ; Hongling SHI ; Ruiying YU ; Xia XIN ; Xiaohuan CHEN ; Li WANG ; Zhiwei ZHI ; Lei TAN ; Xican ZHENG
Chinese Medical Ethics 2024;37(11):1366-1377
Objective:To construct the quality evaluation scale of specification of management for humanistic caring in outpatients and test its reliability and validity.Methods:Referring to the group standards in Specification of Management for Humanistic Caring in Outpatients released by the China Association for Life Care,as well as relevant guidelines and literature,a pool of items for the quality evaluation scale of specification of management for humanistic caring in outpatients was formed.After expert consultation and expert argumentation,a quality evaluation scale of specification of management for humanistic caring in outpatients was constructed.From January to February 2024,243 hospital managers from 5 hospitals in Zhengzhou were selected as survey subjects to conduct item analysis,and reliability and validity testing on the scale.Results:Two rounds of expert inquiry and two rounds of expert argumentation were conducted,with questionnaire response rates of 92.00%and 100.00%,respectively,and expert authority coefficients of 0.952.In the second round of the expert inquiry scale,the mean importance score of the first-level indicators was 4.80 to 5.00,the full score ratio was 88.00%to 100.00%,the coefficient of variation was 0.04 to 0.17,and Kendall's coefficient of concordance was 0.857(P<0.001);the mean importance score of the second-level indicators was 4.60 to 5.00,the full score ratio was 80.00%to 100.00%,the coefficient of variation was 0.00 to 0.21,and Kendall's coefficient of concordance was 0.775(P<0.001);the mean importance score of the third-level indicators was 4.60 to 5.00,the full score ratio was 76.00%to 100.00%,the coefficient of variation was 0.00 to 0.21,and Kendall's coefficient of concordance was 0.830(P<0.001).Finally,a quality evaluation scale of specification of management for humanistic caring in outpatients was formed,including 5 first-level indicators,25 second-level indicators,and 58 third-level indicators.Exploratory factor analysis produced 5 common factors with a cumulative variance contribution rate of 74.628%.The Pearson correlation coefficients between the five-factor scores ranged from 0.648 to 0.798,and the correlation coefficients between the factor scores and the total score of the scale ranged from 0.784 to 0.938.The scale-level content validity index(S-CVI)of the scale was 0.945,the item-content validity index(I-CVI)was 0.725 to 1.000,the Cronbach's alpha coefficient of the total scale was 0.973,and the retest reliability coefficient was 0.934.Conclusion:The constructed quality evaluation scale of specification of management for humanistic caring in outpatients has good scientific validity and reliability,and can be used as an evaluation tool for specification of management for humanistic caring in outpatients.
7.Annual review of clinical research on extracorporeal life support in 2023
Hongling ZHANG ; Yuan YU ; Dechang CHEN ; You SHANG
Chinese Critical Care Medicine 2024;36(2):118-123
The clinical research in the field of extracorporeal life support (ECLS) in 2023 has focused on the efficacy of veno-arterial extracorporeal membrane oxygenation (ECMO) in patients with infarct-related cardiogenic shock. Additionally, the research also explored the efficacy of prone positioning during veno-venous ECMO, transfusion strategies, and the impact of obesity on outcomes. Awake veno-venous ECMO has shown novel therapeutic potential, but its optimal practice methods and management strategies remain to be determined. In in-hospital cardiac arrest patients, extracorporeal cardiopulmonary resuscitation has demonstrated higher survival rates and better neurological recovery compared to conventional cardiopulmonary resuscitation. The effectiveness of extracorporeal carbon dioxide removal varies among patients with different types of respiratory failure. Future research should focus on optimizing the application strategies and process management of ECLS technologies, investigating personalized therapy, and studying how to improve long-term rehabilitation and quality of life for survivors.
8.Advances in research and application of ionizing radiation biomarkers
Hongling OU ; Wenchao AI ; Yan WANG ; Yingying MA ; Lei SHI ; Qiaoyun ZHANG ; Xiujun SONG ; Xinru WANG
Chinese Journal of Pharmacology and Toxicology 2024;38(1):70-78
Exposure to ionizing radiation intervenes in genomic stability and gene expression,resulting in the disruption of normal metabolic processes in cells and organs by causing complex biolog-ical responses.Altered genomic variations,gene expression and metabolite concentrations in blood or tissue samples reflect systemic radiation damage.With the application of new techniques and exten-sive study on the mechanisms for ionizing radiation damage,related indicators such as chromosomal variation,gene expression,lipid and metabolism are being recognized and promise to be the markers for early diagnosis and prognosis of radiation exposure.Therefore,this article reviews recent progress in and potential applications of biomarkers related to ionizing radiation injury.
9.Two case reports of rare antisynthetase syndrome and literature review
Dongbin JIANG ; Yinli ZHANG ; Wenjuan GUAN ; Lei ZHANG ; Hongling ZENG ; Xin ZHANG ; Shengyun LIU ; Guanmin GAO
Chinese Journal of Rheumatology 2024;28(2):123-126
Objective:To study the clinical and immunological features of two case of rare antisynthetase syndrome (ASS), so as to improve the level of diagnosis and treatment.Methods:Two cases with rare antisynthetase syndrome admitted to the First Affiliated Hospital of Zhengzhou University from July 2020 to August 2022 were collected.Results:The two rare ASS were anti-Zo antibody and anti-Ha antibody positive patients, both of which had interstitial lung disease (ILD) as the main clinical manifestation and positive anti-Ro52 antibody. Two rare antisynthetase autoantibodies manifested cytoplasmic ANA indirect immunofluorescence (IIF) staining pattern, but it is different from the cytoplasmic dense speckled pattern of several common ASS antibodies. After treatment with glucocorticoids and immunosuppressants, case 1 died of respiratory failure due to a long course of disease and late diagnosis, the lung lesions of case 2 improved significantly.Conclusion:When encountering the cytoplasmic ANA fluorescent pattern in ILD patients, especially with anti-Ro52 antibody, it is necessary to screen more myositis specific antibodies to rule out the possibility of rare ASS.
10.To investigate the correlation between moderate intensity aerobic exercise and cerebral blood flow regulation in mild stenosis of the carotid artery
Xin PAN ; Yanan ZHANG ; Shubei MA ; Shuhan LIU ; Xiaowen SUI ; Haibin LIU ; Furong LI ; Zusheng LI ; Hongling ZHAO
Chinese Journal of Postgraduates of Medicine 2024;47(8):694-699
Objective:To investigate the correlation between moderate intensity aerobic exercise and cerebral blood flow regulation in patients with mild carotid artery stenosis.Methods:A retrospective study was conducted to select 30 cases of patients with unilateral mild carotid artery stenosis and moderate intensity aerobic exercise for more than 1 year in the Central Hospital of Dalian University of Technology from July 2022 to November 2023 as the exercise group (study group), and 30 cases of patients with unilateral mild carotid artery stenosis without exercise habits matched by age, gender and other factors as the non-exercise group (control group). Transcranial Doppler ultrasound (TCD) examination was performed in both groups, and the recumbent-upright-test, breath holding test and breath exchange test were performed to calculate the occurrence rate of "w" wave in recumbent-upright position, the slope of "w" wave in recubitus position, the change rate of pulse index (PI) before and after breath holding, resistance index (RI), breath holding index (BHI), and cerebral blood flow velocity before and after breath exchange. The blood pressure and heart rate difference in the recumbent-upright position were calculated, and the correlation between moderate intensity aerobic exercise and cerebral blood flow regulation function in patients with mild carotid artery stenosis was evaluated by statistical analysis. The correlation analysis between the exercise years and BHI in the study group was carried out to explore the relationship between the exercise years and cerebrovascular reactivity.Results:The occurrence rate and slope of "w" wave in the study group were higher than those in the control group: 93.3%(28/30) vs. 86.7%(26/30), 2.27 ± 1.14 vs. 1.28 ± 0.23, 2.67 ± 0.63 vs. 1.41 ± 0.69, there were statistically significant ( P<0.05). The change rates of PI and RI before and after breath holding and ventilation in the study group were higher than those in the control group: 21.23 ± 7.67 vs. 13.89 ± 9.67, 14.62 ± 6.63 vs. 11.17 ± 1.78 and 26.26 ± 12.46 vs. 18.36 ± 12.13, 14.91 ± 4.91 vs. 10.83 ± 2.35, and the average cerebral blood flow velocity before and after ventilation was higher than that in the control group: (31.26 ± 4.92) cm/s vs. (24.89 ± 6.34) cm/s, there were statistically significant ( P<0.01). The exercise years of the study group was negatively correlated with the breath holding index. Conclusions:Moderate intensity exercise is associated with cerebral blood flow regulation in patients with mild carotid artery stenosis. Exercise years are negatively correlated with cerebral blood flow regulation. Impaired cerebral blood flow regulation may be one of the potential mechanisms of poor prognosis of stroke in carotid artery stenosis population.

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