1.Effect of Huanglian Jiedutang in Regulating Ferroptosis in Mice with Atherosclerosis Based on Nrf2/GPX4 Signaling Pathway
Zhaohui GONG ; Li GAO ; Huiqi ZHAI ; Jinzi YU ; Qingmin CHU ; Chuanjin LUO ; Lijin QING ; Wei WU ; Rong LI
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(3):22-28
ObjectiveTo study the mechanism of Huanglian Jiedutang (HLJDT) in treating mice with atherosclerosis (AS) by improving ferroptosis. MethodsA total of 10 SPF C57BL/6J mice were selected as a normal group, and 50 ApoE-/- mice were randomly divided into five groups: model group, low-dose group of HLJDT, medium-dose group of HLJDT, high-dose group of HLJDT, and atorvastatin (ATV) group. ApoE-/- mice were fed a high-fat diet for eight weeks to establish the AS model, and at the 9th week, they were given normal saline, low, medium, and high doses of HLJDT (3.9, 7.8, 15.6 g·kg-1·d-1), and atorvastatin calcium tablets (0.01 g·kg-1·d-1), respectively, for a total of eight weeks. The formation of aortic plaque in mice was observed by gross oil red O staining and Masson staining. The levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), triglyceride (TG), and high-density lipoprotein cholesterol (HDL-C) in blood fat were measured by the automatic biochemical analyzer, and the mitochondrial structure of the aorta was observed by transmission electron microscopy. The content of serum superoxide dismutase (SOD) in serum was detected by enzyme-linked immunosorbent assay (ELISA). The content of reduced glutathione (GSH) in serum was detected by the microplate method, and that of malondialdehyde (MDA) in serum was detected by the TBA method. The protein expression of nuclear factor E2-associated factor 2 (Nrf2)/glutathione peroxidase 4 (GPX4) signaling pathway was detected by Western blot. ResultsCompared with those of the normal group, the contents of TC, LDL-C, TG, HDL-C, and MDA in the serum and the aortic vascular plaque deposition of the model group were significantly increased (P<0.01), while the expression levels of SOD and GSH in serum, as well as Nrf2, solute carrier family 7 member 11 (SLC7A11), and GPX4 in aorta were significantly decreased (P<0.01). Mice in the model group appeared mitochondrial fragmentation and vacuolation in the aorta, volume atrophy, mitochondrial crista reduction, or a loose and disorganized form. Compared with those in the model group, the aortic vascular plaque deposition was significantly decreased in the low-dose, medium-dose, and high-dose groups of HLJDT and ATV group, and the contents of serum TC, LDL-C, TG, and MDA in serum were significantly decreased (P<0.05, P<0.01). The contents of serum SOD and GSH and the expression levels of Nrf2, SLC7A11, and GPX4 in the aorta were increased (P<0.05, P<0.01), and the symptoms of aortic mitochondrial vacuolation were alleviated. The number of cristae was increased, and they were ordered neatly. ConclusionHLJDT can reduce aortic vascular plaque deposition, decrease blood lipid and MDA expression, increase SOD and GSH expression, and ameliorate the pathological changes of ferroptosis, the mechanism of which is related to the Nrf2/GPX4 signaling pathway.
2.Antioxidant and Anti-tumor Effect and Mechanisms of Andrographis paniculata Polysaccharide on Human Cervical Cancer HeLa Cells
Lijin HUANG ; Zilin LI ; Ziyan YANG ; Han WANG ; Guiyuan CHEN
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(18):80-88
ObjectiveTo explore the antioxidant and anti-human cervical cancer HeLa cell effect and mechanisms of Andrographis paniculata polysaccharide (APP). MethodCell function assays were conducted to assess the effects of APP (400, 450, 500 mg·L-1) on the proliferation, migration, and invasion of HeLa cells using the cell counting kit-8 (CCK-8) assay, scratch assay, and Transwell assay. Molecular mechanism experiments were conducted to detect the effects of APP on HeLa cell apoptosis and cell cycle-related mRNA and protein expression using flow cytometry, real-time fluorescence-based quantitative polymerase chain reaction (Real-time PCR), and Western blot analysis. The antioxidant activity of APP was tested using DPPH+, OH-, and reducing power assays. ResultCompared with the blank group, APP (400, 450, 500 mg·L-1) significantly inhibited the migration, proliferation, and invasion abilities of HeLa cells in a time- and dose-dependent manner (P<0.05, P<0.01). Flow cytometry with propidium iodide (PI) single staining was used to detect cell cycle. The results showed that compared with the blank group, the proportion of HeLa cells in the G2/M phase increased after 48 hours of treatment with APP (400, 450, 500 mg·L-1), indicating that APP can arrest HeLa cells in the G2/M phase. Flow cytometry with fluorescein isothiocyanate (Annexin V-FITC)/PI apoptosis kit was used to detect cell apoptosis. Compared with the blank group, the proportion of early and late apoptotic HeLa cells increased in a dose-dependent manner after 48 hours of APP (400, 450, 500 mg·L-1) treatment (P<0.05, P<0.01), indicating that APP promotes HeLa cell apoptosis. The results of Real-time PCR and Western blot assay showed that compared with the blank group, after 48 hours of APP (400, 450, 500 mg·L-1) treatment resulted in decreased mRNA and protein expression of cell cycle-dependent kinase-1 (CDK-1), Cyclin B1, and B-cell lymphoma-2 (Bcl-2), and increased mRNA and protein expression of cysteine aspartate protease (Caspase)-3, Caspase-8, Caspase-9, and Bcl-2-associated X protein (Bax) (P<0.05, P<0.01). These findings were consistent with the flow cytometry results and showed a dose-dependent effect. In vitro antioxidant tests demonstrated that different concentrations of APP (50-1 000 mg·L-1) were able to scavenge DPPH+ and OH- radicals, indicating certain antioxidant activity. ConclusionAPP possesses antioxidant activity and can inhibit the viability of HeLa cells while promoting their apoptosis.
3.Interpretation of the Pituitary Society International Consensus of Diagnosis and Management of Prolactin-Secreting Pituitary Adenomas
Lijin JI ; Bin LU ; Hongying YE ; Yiming LI
Chinese Journal of Endocrinology and Metabolism 2024;40(5):365-372
The Pituitary Society released the 2023 International Consensus on the Diagnosis and Treatment of Prolactin-Secreting Adenomas, marking another update following the guidelines from the Endocrine Society in 2006 and 2011. Published in Nature Reviews Endocrinology, this consensus is based on the latest research evidence in recent years, covering topics such as the efficacy, long-term adverse effects, and withdrawal protocols of dopamine receptor agonists, as well as indications for surgery, preoperative medical therapy, and radiation therapy. It comprehensively discusses the treatment of prolactin-secreting adenomas in special periods and conditions. This article provides a detailed interpretation of the core recommended points in the consensus, focusing on four major aspects: diagnosis, treatment, special populations, and rare conditions of prolactinoma, aiming to help clinicians gain a comprehensive understanding of the consensus and provide assistance in clinical management.
4.Risk factors and development of a risk assessment model for postoperative venous thromboembolism in Cushing′s disease
Wenjuan LIU ; Dan LIU ; Min HE ; Qing MIAO ; Lijin JI ; Lili CHEN ; Yifei YU ; Zengyi MA ; Xuefei SHOU ; Shuo ZHANG ; Yutao WANG ; Zhiyuan WU ; Chaoyun ZHANG ; Yao ZHAO ; Yiming LI ; Yongfei WANG ; Hongying YE
Chinese Journal of Endocrinology and Metabolism 2024;40(6):487-493
Objective:To investigate the incidence and prothrombotic risk factors of postoperative venous thromboembolism(VTE) in Cushing′s disease and to further develop an assessment model to identify those at high risk of postoperative VTE events.Methods:A retrospective study was performed in 82 patients who were admitted to Huashan Hospital, Fudan University during January 2019 and January 2020 and diagnosed with Cushing′s disease. These patients underwent the evaluation about their clinical, hormonal, and coagulation parameters, as well as ultrasonography and pulmonary angio-CT when necessary. The least absolute shrinkage and selection operator(LASSO) regression analysis was used to screen independent risk factors, and a nomogram model for postsurgical VTE risk assessment in Cushing′s disease was initially established, and Bootstrap method was used for internal verification. Finally, the predictive model was evaluated for calibration and clinical applicability in the study cohort.Results:Nineteen patients(23.17%) developed VTE events, with 14 cases occurring after endoscopic transsphenoidal surgery. Compared to patients without VTE, those in the VTE group were older( P<0.001), had longer postoperative bed rest, higher rates of current infection, higher HbA 1C levels, and more severe glucose tolerance impairment(all P<0.05). Through LASSO regression analysis, two independent risk factors for postoperative VTE were identified: Age and current infection. Then a VTE risk assessment nomogram model was established to predict the patients at high risk of VTE. In the nomogram model for VTE risk assessment, the area under the receiver operating characteristic curve was 0.868(95% CI 0.787-0.949), with the calibration curve closely aligning with the ideal diagonal line and the clinical decision curve exceeding the two extreme curves. Conclusions:Advanced perioperative assessment needs to be taken to screen those with high VTE risks in patients diagnosed with Cushing′s disease. Additionally, during the perioperative period, patients with Cushing′s disease should undergo mandatory physical activity or prophylactic anticoagulant therapy.
5.Renal diabetes insipidus caused by Sj?gren′s syndrome
Xiaoxia LIU ; Lijin JI ; Lingbiao WANG ; Lin LU ; Yu XUE ; Jun XUE ; Yiming LI ; Bin LU
Chinese Journal of Endocrinology and Metabolism 2024;40(8):697-701
We present a case of nephrogenic diabetes insipidus secondary to primary Sj?gren′s syndrome. At onset, the patient exhibited a urine output of up to 10 liter per day. Diagnostic evaluation and clinical features confirmed renal diabetes insipidus due to primary Sj?gren′s syndrome. A review of the literature indicates that primary Sj?gren′s syndrome can involve renal manifestations, including renal tubulointerstitial inflammation and impaired renal concentration ability. However, nephrogenic diabetes insipidus with such high urine output is uncommon. Management of this condition requires proactive control of the underlying disease, potassium supplementation, and urine management.
6.Expression changes of miRNAs and EMT-related genes in human mesothelial cells induced by long-term exposure to asbestos
Rui LI ; Wenke YU ; Qi WANG ; Lijin ZHU ; Fangfang ZHANG
Chinese Journal of Industrial Hygiene and Occupational Diseases 2024;42(9):668-672
Objective:To investigate the effects of long-term exposure to chrysotile and crocidolite on miRNAs and epithelial mesenchymal transformation (EMT) -related gene expression in human pleural mesothelial cells.Methods:In November 2020, fluorescence quantitative polymerase chain reaction (RT-qPCR) was used to detect the expressions of EMT-related genes in human pleural mesothelioma cells (NCl-H2052 cells, NCl-H2452 cells) and human normal mesothelial cells (Met-5A cells). MiRNAs with abnormal expression in human pleural mesothelioma cells were screened out from the previous miRNA chip data of research group, and target genes of differentially expressed miRNAs were predicted using miRWalk database (http: //mirwalk.umm.uni-heidelberg.de). RT-qPCR was used to verify the abnormal expression of EMT-related miRNAs in cell lines. Met-5A cells were treated with 5μg/cm 2 chrysotile and crocidolite respectively for 48 h a time, once a week and a total of 10 times. Chrysotile group, crocidolite group and control group were set up. And the control group was added with the same volume of PBS. The expression changes of EMT-related genes and abnormal expression miRNAs in each group were detected by RT-qPCR. The differences among the groups were compared by one-way ANOVA, and the differences between the control group and the experimental group were compared by dunnet- t test. Results:Compared with Met-5A cells, the expression levels of Vimentin and Twist genes were increased, and the expression level of E-cadherin genes was decreased in NCl-H2052 cells and NCl-H2452 cells ( P<0.001). Target genes of miRNAs with abnormal expression in miRNA chip were predicted, and the results showed four abnormally expressed miRNAs associated with EMT and verified the expression of these four miRNAs in the cell lines. Compared with Met-5A cells, the expression level of hsa-miR-155-5p was increased in NCl-H2052 cells and NCl-H2452 cells, the expression levels of hsa-miR-34b-5p, hsa-miR-34c-5p and hsa-miR-28-5p were decreased in NCl-H2052 cells and NCl-H2452 cells ( P<0.001), which was consistent with the results of chip analysis. After exposure of Met-5A cells, it was found that compared with the control group, the expression levels of Vimentin and Twist genes, hsa-miR-155-5p, hsa-miR-34b-5p and hsa-miR-34c-5p in the crocidolite group were increased, while the expression level of E-cadherin gene was decreased ( P<0.05). Compared with the control group, the expression levels of Vimentin, Twist and E-cadherin genes in chrysotile group were increased, while the expression levels of hsa-miR-34b-5p, hsa-miR-34c-5p and hsa-miR-28-5p were decreased ( P<0.05) . Conclusion:Long-term exposure to chrysotile and crocidolite could cause Met-5A cells to produce miRNAs and EMT-related gene expression changes similar to mesothelioma cells.
7.Expression changes of miRNAs and EMT-related genes in human mesothelial cells induced by long-term exposure to asbestos
Rui LI ; Wenke YU ; Qi WANG ; Lijin ZHU ; Fangfang ZHANG
Chinese Journal of Industrial Hygiene and Occupational Diseases 2024;42(9):668-672
Objective:To investigate the effects of long-term exposure to chrysotile and crocidolite on miRNAs and epithelial mesenchymal transformation (EMT) -related gene expression in human pleural mesothelial cells.Methods:In November 2020, fluorescence quantitative polymerase chain reaction (RT-qPCR) was used to detect the expressions of EMT-related genes in human pleural mesothelioma cells (NCl-H2052 cells, NCl-H2452 cells) and human normal mesothelial cells (Met-5A cells). MiRNAs with abnormal expression in human pleural mesothelioma cells were screened out from the previous miRNA chip data of research group, and target genes of differentially expressed miRNAs were predicted using miRWalk database (http: //mirwalk.umm.uni-heidelberg.de). RT-qPCR was used to verify the abnormal expression of EMT-related miRNAs in cell lines. Met-5A cells were treated with 5μg/cm 2 chrysotile and crocidolite respectively for 48 h a time, once a week and a total of 10 times. Chrysotile group, crocidolite group and control group were set up. And the control group was added with the same volume of PBS. The expression changes of EMT-related genes and abnormal expression miRNAs in each group were detected by RT-qPCR. The differences among the groups were compared by one-way ANOVA, and the differences between the control group and the experimental group were compared by dunnet- t test. Results:Compared with Met-5A cells, the expression levels of Vimentin and Twist genes were increased, and the expression level of E-cadherin genes was decreased in NCl-H2052 cells and NCl-H2452 cells ( P<0.001). Target genes of miRNAs with abnormal expression in miRNA chip were predicted, and the results showed four abnormally expressed miRNAs associated with EMT and verified the expression of these four miRNAs in the cell lines. Compared with Met-5A cells, the expression level of hsa-miR-155-5p was increased in NCl-H2052 cells and NCl-H2452 cells, the expression levels of hsa-miR-34b-5p, hsa-miR-34c-5p and hsa-miR-28-5p were decreased in NCl-H2052 cells and NCl-H2452 cells ( P<0.001), which was consistent with the results of chip analysis. After exposure of Met-5A cells, it was found that compared with the control group, the expression levels of Vimentin and Twist genes, hsa-miR-155-5p, hsa-miR-34b-5p and hsa-miR-34c-5p in the crocidolite group were increased, while the expression level of E-cadherin gene was decreased ( P<0.05). Compared with the control group, the expression levels of Vimentin, Twist and E-cadherin genes in chrysotile group were increased, while the expression levels of hsa-miR-34b-5p, hsa-miR-34c-5p and hsa-miR-28-5p were decreased ( P<0.05) . Conclusion:Long-term exposure to chrysotile and crocidolite could cause Met-5A cells to produce miRNAs and EMT-related gene expression changes similar to mesothelioma cells.
8.Research on Water Extraction Process of Flos Lonicerae-Fructus Forsythuae Based on Network Pharmacology and Design Space
Ting CUI ; Meizhou LI ; Lifan GAN ; Jiaming LIN ; Lijin LIANG ; Xingpeng HUANG ; Zhipeng ZHANG
Journal of Nanjing University of Traditional Chinese Medicine 2024;40(1):47-60
OBJECTIVE To optimize the water extraction process of Flos Lonicerae-Fructus Forsythuae and determine the range of water extraction process parameters.METHODS The active components were screened by network pharmacology,and the indica-tor ingredients were determined in combination with the quality markers under the relevant terms of Chinese Pharmacopoeia 2020 edition and the literature.Take extraction yield and the extraction rate of the indicative component as the critical quality attributes of the water extraction process to screen critical process parameters.The mathematical model was established by Box-Behnken experimental design to investigate the interaction between CQAs and CPPs and build the design space of the water extraction process of Flos Lonicerae-Fruc-tus Forsythuae.RESULTS The extraction percentages of phenolic acids,forsythoside A and forsythin were screened as the index components;specifications of medicinal slices,extraction time and water addition were the key process parameters.Based on the estab-lishment and optimization of the design space,the optimum water extraction process was obtained as follows:the medicinal slice of Lian-Qiao was broken into 0.8-1.2 cm,adding 12 times the amount of water in the first and extract for 30-50 min,10 times the a-mount of water in the second and extract for 25-30 min.CONCLUSION The verification results show that the measured value ob-tained by using the design space method to optimize the water extraction process is close to the predicted value,indicating that the method is stable and reliable,which can provide ideas for its further process development and quality control for the couple medicines of Flos Lonicerae-Fructus Forsythuae.
9.Exploration of the mechanism for medical communication and humanistic quality cultivation from the perspective of narrative medicine
Miao GUO ; Dong LI ; Yingjie GUO ; Kun GUAN ; Sheng TIAN ; Lijin YANG ; Zhe WANG
Modern Hospital 2024;24(10):1504-1507
Narrative medicine,as an interdisciplinary field at the intersection of humanistic education and medical edu-cation,is an effective means of implementing medical humanities.It not only fosters deeper empathy and communication between doctors and patients but also plays an important role in clinical practice and the cultivation of humanistic qualities.This study starts from the core connotation of integrating narrative medicine into the doctor-patient relationship,focusing on the value logic of narrative medicine empowering humanistic care.Utilizing a typical case from a hospital in Tianjin that practices humanistic care based on narrative medicine,the study examines the organizational structure,practical activities,humanistic care initiatives,health education,supportive measures,and outcomes of the narrative medicine healthcare management team.The conclusion drawn is that exploring mechanisms for medical communication and the cultivation of humanistic qualities can facilitate the mutual transformation of narrative and empathy skills,the organic combination of narrative medicine with evidence-based medicine,and the complementary relationship between clinical medicine and humanistic education.This approach aims to alleviate the increas-ingly prominent conflicts between doctors and patients,bridge the gap between humanity and technology,and promote the imple-mentation of medical humanities in clinical settings.
10.Effect of Bakri balloon tamponade combined with oxytocin on postpartum hemorrhage after cesarean section and its effect on coagulation function
Chinese Journal of Postgraduates of Medicine 2024;47(6):518-522
Objective:To investigate the effect of Bakri balloon tamponade combined with oxytocin in the treatment of postpartum hemorrhage after cesarean section and its effect on coagulation function.Methods:Fifty patients with cesarean section and postpartum hemorrhage treated in Hainan Modern Women and Children′s Hospital from May 2018 to May 2021 were enrolled retrospectively, and they were randomly divided into observation group and control group, each with 25 cases. The control group was treated with oxytocin combined with intrauterine gauze to stop bleeding, and the observation group was treated with oxytocin combined with Bakri balloon to stop bleeding. The clinical efficacy and hemostatic effect of the two groups were compared. The heart rate, blood pressure, coagulation function before and after treatment and postoperative complications were compared between the two groups.Results:The total effective rate in the observation group was higher than that in the control group: 92.00%(23/25) vs. 68.00%(17/25), there was statistical difference ( χ2 = 4.50, P<0.05). The hemostasis time, intraoperative bleeding volume, 24 h postpartum bleeding volume and blood transfusion volume in the observation group were lower than those in the control group: (11.25 ± 2.54) min vs. (20.56 ± 4.87) min, (687.53 ± 102.84) ml vs. (789.25 ± 113.47) ml, (915.23 ± 115.62) ml vs. (1 041.65 ± 125.83) ml, (1 054.28 ± 186.73) ml vs. (1 207.58 ± 193.72) ml, there were statistical differences ( P<0.05). After treatment, the heart rate, diastolic blood pressure and systolic blood pressure in the observation group were lower than those in the control group: (85.17 ± 8.73) beats/min vs. (92.75 ± 9.05) beats/min, (81.25 ± 8.34) mmHg (1 mmHg = 0.133 kPa) vs. (90.12 ± 8.83) mmHg , (120.27 ± 15.17) mmHg vs. (132.71 ± 16.27) mmHg , there were statistical differences ( P<0.05). After treatment, the levels of prothrombin time and activated partial thromboplastin time in the observation group were lower than those in the control group, and the level of fibrinogen in the observation group was higher than that in the control group: (13.15 ± 1.28) s vs. (17.36 ± 1.58) s, (30.36 ± 6.75) s vs. (38.47 ± 7.38) s, (6.17 ± 1.02) g/L vs. (5.25 ± 0.97) g/L, there were statistical differences ( P<0.05). The incidence of postoperative complications in the observation group was lower than that in the control group: 12.00% (3/25) vs. 36.00%(9/25), there was statistical difference ( χ2 = 3.95, P<0.05). Conclusions:Bakri balloon tamponade combined with oxytocin can significantly improve the coagulation function of patients with postpartum hemorrhage after cesarean section, reduce the occurrence of postoperative complications.

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