1.Mechanism of Danshenol A in Alleviating Myocardial Ischemia-reperfusion Injury-induced Ferroptosis of Cardiomyocytes
Lei ZHANG ; Jiangang LIU ; Peili WANG ; Tao GENG ; Die LIN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(11):135-144
ObjectiveTo investigate the mechanism of danshenol A (DA) pretreatment in alleviating myocardial ischemia-reperfusion injury (MIRI) by regulating cardiomyocyte ferroptosis by in vivo and in vitro experiments. MethodsA MIRI model was established in SD rats, and an in vitro oxygen-glucose deprivation/reoxygenation (OGD/R) model was constructed with H9C2 cells. Both models were treated with DA. H9C2 cells were allocated into blank, model (OGD/R), DA, ferroptosis inducer (erastin), and ferroptosis inhibitor (Fer-1) groups. Cell viability was assessed by the methyl thiazolyl tetrazolium (MTT) assay. Biochemical assays were performed to measure the superoxide dismutase (SOD), malondialdehyde (MDA), glutathione (GSH), and ferrous ion (Fe2+) levels. Dihydroethidium (DHE) fluorescence assay was adopted to quantify the reactive oxygen species (ROS) level. Real-time PCR and Western blot were employed to quantify the mRNA and protein levels, respectively, of prostaglandin-endoperoxide synthase 2 (PTGS2), glutathione peroxidase 4 (GPX4), ferritin heavy chain 1 (FTH1), and acyl-coA synthetase long-chain family 4 (ACSL4). Sixty SPF-grade healthy male SD rats were randomly assigned to control, model (MIRI), DA, erastin, and Fer-1 groups. Enzyme-linked immunosorbent assay (ELISA) was adopted to measure the serum levels of cardiac troponin I (cTnI), lactate dehydrogenase (LDH), and creatine kinase (CK). Histopathological changes in the myocardial tissue were observed by hematoxylin-eosin (HE) staining. Cardiomyocyte apoptosis was detected by terminal deoxynucleotidyl transferase-mediated nick end labeling (TUNEL). The effect of DA on cardiomyocyte ferroptosis were observed and analyzed by in vivo and in vitro experiments. ResultsIn vitro experiment: compared with the blank group, the OGD/R model group showed reduced cell viability, elevated levels of ROS, MDA, and Fe2+, up-regulated mRNA and protein levels of ACSL4, lowered levels of SOD and GSH, and down-regulated mRNA and protein levels of PTGS2, GPX4, and FTH1 (P<0.05,P<0.01). The DA and Fer-1 groups exhibited consistent trends: cell viability, SOD and GSH levels, and the mRNA and protein levels of PTGS2, GPX4, and FTH1 were significantly restored, while the ROS, MDA, and Fe2+ levels, and the mRNA and protein levels of ACSL4 were reduced (P<0.05,P<0.01). In vivo experiment: Compared with the control group, the MIRI model group showed elevated serum levels of cTnI, LDH, and CK, increased cardiomyocyte apoptosis rate, risen levels of ROS, MDA, and Fe2+, and up-regulated mRNA and protein levels of ACSL4. However, both DA and Fer-1 groups exhibited reductions in the indicators above (P<0.05). Compared with the control group, the MIRI model group demonstrated reduced levels of SOD and GSH and down-regulated mRNA and protein levels of PTGS2, GPX4, and FTH1 (P<0.05). In contrast, both DA and Fer-1 upregulated these indicators (P<0.05), effectively reversing the trends in the model group. In addition, the MIRI model group showed swelling of cardiomyocytes, disarrangement of cardiac muscle fibers, and massive inflammatory cell infiltration, which were alleviated in the DA and Fer-1 groups. ConclusionDA alleviates MIRI by inhibiting ferroptosis and inflammation, demonstrating therapeutic potential in acute myocardial infarction.
2.Mechanism of Danshenol A in Alleviating Myocardial Ischemia-reperfusion Injury-induced Ferroptosis of Cardiomyocytes
Lei ZHANG ; Jiangang LIU ; Peili WANG ; Tao GENG ; Die LIN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(11):135-144
ObjectiveTo investigate the mechanism of danshenol A (DA) pretreatment in alleviating myocardial ischemia-reperfusion injury (MIRI) by regulating cardiomyocyte ferroptosis by in vivo and in vitro experiments. MethodsA MIRI model was established in SD rats, and an in vitro oxygen-glucose deprivation/reoxygenation (OGD/R) model was constructed with H9C2 cells. Both models were treated with DA. H9C2 cells were allocated into blank, model (OGD/R), DA, ferroptosis inducer (erastin), and ferroptosis inhibitor (Fer-1) groups. Cell viability was assessed by the methyl thiazolyl tetrazolium (MTT) assay. Biochemical assays were performed to measure the superoxide dismutase (SOD), malondialdehyde (MDA), glutathione (GSH), and ferrous ion (Fe2+) levels. Dihydroethidium (DHE) fluorescence assay was adopted to quantify the reactive oxygen species (ROS) level. Real-time PCR and Western blot were employed to quantify the mRNA and protein levels, respectively, of prostaglandin-endoperoxide synthase 2 (PTGS2), glutathione peroxidase 4 (GPX4), ferritin heavy chain 1 (FTH1), and acyl-coA synthetase long-chain family 4 (ACSL4). Sixty SPF-grade healthy male SD rats were randomly assigned to control, model (MIRI), DA, erastin, and Fer-1 groups. Enzyme-linked immunosorbent assay (ELISA) was adopted to measure the serum levels of cardiac troponin I (cTnI), lactate dehydrogenase (LDH), and creatine kinase (CK). Histopathological changes in the myocardial tissue were observed by hematoxylin-eosin (HE) staining. Cardiomyocyte apoptosis was detected by terminal deoxynucleotidyl transferase-mediated nick end labeling (TUNEL). The effect of DA on cardiomyocyte ferroptosis were observed and analyzed by in vivo and in vitro experiments. ResultsIn vitro experiment: compared with the blank group, the OGD/R model group showed reduced cell viability, elevated levels of ROS, MDA, and Fe2+, up-regulated mRNA and protein levels of ACSL4, lowered levels of SOD and GSH, and down-regulated mRNA and protein levels of PTGS2, GPX4, and FTH1 (P<0.05,P<0.01). The DA and Fer-1 groups exhibited consistent trends: cell viability, SOD and GSH levels, and the mRNA and protein levels of PTGS2, GPX4, and FTH1 were significantly restored, while the ROS, MDA, and Fe2+ levels, and the mRNA and protein levels of ACSL4 were reduced (P<0.05,P<0.01). In vivo experiment: Compared with the control group, the MIRI model group showed elevated serum levels of cTnI, LDH, and CK, increased cardiomyocyte apoptosis rate, risen levels of ROS, MDA, and Fe2+, and up-regulated mRNA and protein levels of ACSL4. However, both DA and Fer-1 groups exhibited reductions in the indicators above (P<0.05). Compared with the control group, the MIRI model group demonstrated reduced levels of SOD and GSH and down-regulated mRNA and protein levels of PTGS2, GPX4, and FTH1 (P<0.05). In contrast, both DA and Fer-1 upregulated these indicators (P<0.05), effectively reversing the trends in the model group. In addition, the MIRI model group showed swelling of cardiomyocytes, disarrangement of cardiac muscle fibers, and massive inflammatory cell infiltration, which were alleviated in the DA and Fer-1 groups. ConclusionDA alleviates MIRI by inhibiting ferroptosis and inflammation, demonstrating therapeutic potential in acute myocardial infarction.
3.Analysis of 23 cases of spontaneous perirenal urine extravasation after urinary tract obstruction
Peili MA ; Haitao DAI ; Zhong ZHANG ; Yuanhua LIU ; Peichao GUO ; Zhenxing HU ; Changwei PENG
Journal of Modern Urology 2024;29(10):865-868
[Objective] To investigate the clinical manifestations and explore the experience of diagnosis and treatment of spontaneous perirenal urine extravasation after urinary tract obstruction so as to improve the understanding of the disease. [Methods] The clinical data of 23 patients with spontaneous perirenal urine extravasation after obstruction treated at our hospital during 2018 and 2020 were retrospectively analyzed, including the primary diseases, clinical manifestations, imaging examination, treatment and prognosis. The key points of diagnosis and treatment were summarized. [Results] Of the 23 patients, there were 15 males and 8 females, with an average age of 43.4 years. These cases were diagnosed by imaging tests such as ultrasound, computed tomography urography (CTU) and CT. Ureteroscopic lithotripsy was performed in 3 patients with ureteral calculi, retrograde ureteral catheterization in 4 patients and percutaneous nephrostomy in 13 patients. Afterwards, a second phase surgery was performed based on the patients' condition. Of the 3 patients with tumor metastasis who underwent retrograde ureteral catheterization, 2 operation were successful, and 1 operation failed and then converted to nephrostomy and drainage under B-ultrasound localization. [Conclusion] CTU should be performed as soon as possible to make a definite diagnosis. Treatment can be achieved with ureteral retrograde catheterization or percutaneous nephrostomy to achieve local decompression, followed by secondary surgery to treat the primary cause of obstruction.
4.Survey on the Working Conditions of Doctors Engaged in Rare Diseases and Initial Discussion on Talent Training
Lei ZHANG ; Linfeng ZOU ; Peili JI ; Limeng CHEN
JOURNAL OF RARE DISEASES 2024;3(3):400-404
Background In recent years,rare diseases have become a major public health issue.There is an urgent need to improve the diagnosis and treatment for these diseases,and the training for doctors engaged in rare diseases is an important part of it.Methods This study conducted a questionnaire survey on the doctors engaged in rare diseases in Peking Union Medical College Hospital to better understand their characteristics and evaluate their psychological and working status.Results A total of 95 questionnaires from doctors engaged in rare diseases were collected in this study,among which the female:male ratio was 1.6∶1,and 63.2%of them were in the 40-54 age group.Their main reason for choosing rare diseases was the enjoyment in the process of studying rare diseases(64.2%).Compared with the 108 doctors not engaged in rare diseases surveyed during the same period,those working on rare diseases reported higher patient recognition based on self-evaluation(P<0.001).In terms of the time-consuming work,in addition to routine medical work,teaching and research,34.7%of doctors engaged in rare diseases chose doctor-patient communication and 31.6%chose medical man-agement communication.Conclusions This study proposes some suggestions on the talent training for rare dis-eases,the establishment of continuing education platforms,and the technology and policy support needed through the analysis of the questionnaire survey results of doctors engaged in rare diseases.
5.Method and improvement of implantable osmotic pump for intraventricular drug administration in rats
Heyong SUN ; Gangli ZHANG ; Jiliang WU ; Peili CAO ; Shuo LI ; Haoqin SUN
Chinese Journal of Comparative Medicine 2024;34(7):89-94
Objective To introduce and enhance an experimental technique for intraventricular drug delivery via an implantable osmotic pump.Methods Eight-week-old male SD rats were selected and the requisite equipment and reagents were prepared.The osmotic pump was assembled and brought to operational status before conducting the implantation surgery.Following anesthesia,the rats underwent skin preparation and the upper surface of the skull was surgically exposed.A point directly above the ventricle was located using a brain stereotaxic apparatus,and a small hole was drilled at that location with a high-speed cranial drill.The pump body was then implanted subcutaneously in the neck and the needle was inserted into the drilled hole,and secured with dental cement.Once solidified,the needle base was removed,the subcutaneous soft tissue and scalp were sutured in layers,and the animal was returned to its cage for rearing in isolation.Results The osmotic pump was successfully implanted subcutaneously in the rat's neck,the needle was securely fixed to the skull,and the catheter interface remained intact.The rats were sacrificed and the brain tissue was removed.Examination of the extracted brain tissue revealed no significant hematoma around the puncture site or needle tract,and the presence of blue dye in the ventricular and adjacent tissues indicated successful drug delivery to the ventricle.Conclusions The introduction of a brain stereotaxic apparatus to aid localization,coupled with enhancements to the operational procedure,may improve the accuracy and safety of the implantation process resulting in a high success rate for intraventricular drug administration.
6.Analysis on the value of 2DE combined with CDFI in diagnosing HCM
Yu ZHANG ; Peili AN ; Ning WANG ; Shujuan ZHONG
China Medical Equipment 2024;21(5):83-87
Objective:To observe the value of two-dimensional echocardiography(2DE)combined with color Doppler flow imaging(CDFI)in the diagnosis for hypertrophic cardiomyopathy(HCM).Methods:A total of 480 HCM patients who admitted to Northwest Women's and Children's Hospital from January 2019 to January 2021 were selected as case group,and 200 healthy individuals who underwent health physical examination were included into health control group.All receivers underwent 2DE and CDFI examinations,and the 2DE and CDFI detection indicators of two groups were calculated by statistical method and were compared.The diagnostic efficacies of single 2DE,single CDFI and the combination of them were analyzed.Results:The thickness of left ventricular posterior wall(LVPW),interventricular septum thickness(IVST)and left atrial diameter(LAD)of the case group were significantly higher than those of the control group,and the differences were statistically significant(t=5.896,14.861,8.974,P<0.05),respectively.The E peak/A peak(E/A)of anterior flow of mitral valve and early diastolic velocity of mitral valve(Em)of the case group were respectively lower than those of the health control group,while the early diastolic blood flow velocity of mitral valve opening(E)/Em(E/Em)of the case group was higher than that of the health control group,with statistically significant differences(t=6.782,5.189,10.738,P<0.05).The optimal critical points(detection sensitivity)of the receiver operating characteristic(ROC)curves of single 2DE,single CDFI and combination of them in diagnosing HCM were respectively 67.83%,65.38%and 82.38%.The detection specificities of them were respectively 65.48%,64.58%and 80.66%.The area under curve(AUC)values of ROC curves of them were respectively 0.6835,0.6949 and 0.8136,and the accuracies of them were respectively 68.35%,69.49%and 81.36%,and the 95%confidence intervals of them were respectively 0.608-0.803,0.606-0.823 and 0.835-0.943.The sensitivity,specificity and accuracy of the combination of 2DE and CDFI were respectively higher than those of single 2DE and CDFI.Conclusion:Both 2DE and CDFI have a certain value in diagnosing HCM,but their combination can further improve the diagnostic efficacy for HCM.
7.Application of flipped classroom combined with a case-based learning in genetics courses
Lei ZHANG ; Peili JI ; Cai YUE ; Xiuli ZHAO ; Yaping LIU ; Limeng CHEN
Basic & Clinical Medicine 2024;44(9):1331-1334
In recent years,with the development of gene testing and new drug research,the diagnosis and treatment of inherited diseases have made rapid progress,corresponding to higher requirements for genetics education.As a teacher of medical genetics,the author joined the course remodeling during last 10 years from a web-based study of genetic disorders to a"case-based learning"supported by flipped classroom in order to optimize teaching effects and learning outcomes.The result of this remodeling project proposes a new strategy to guide perspectives course de-sign in future.
8.Application of discharge preparation services in patients undergoing uniportal video-assisted thoracoscopic surgery for lung cancer
Qianqian SONG ; Aihong PAN ; Qing ZHANG ; Peili XU ; Shanshan LUO
Chinese Journal of Modern Nursing 2024;30(31):4270-4275
Objective:To explore the effect of discharge preparation services in patients undergoing uniportal video-assisted thoracoscopic surgery for lung cancer.Methods:A total of 192 lung cancer patients who underwent uniportal video-assisted thoracoscopic surgery between April 2021 and May 2023 were selected using a convenience sampling method. The 97 patients admitted from April 2021 to April 2022 were designated as the control group and received routine care, while the 95 patients admitted from May 2022 to May 2023 were designated as the observation group and received discharge preparation services. Postoperative recovery indicators (e.g., time to first meal, time to first ambulation), the Readiness for Hospital Discharge Scale (RHDS), the Chinese version of the Functional Assessment of Cancer Therapy-Lung (FACT-L), and the nursing service satisfaction questionnaire were used to evaluate the intervention's effects.Results:The observation group had significantly shorter times to first meal, first ambulation, and drain removal, as well as lower complication rates compared to the control group, with statistically significant differences ( P<0.05). After the intervention, the RHDS, FACT-L, and nursing service satisfaction questionnaire scores were significantly higher in the observation group compared to the control group, with statistically significant differences ( P<0.05) . Conclusions:The application of discharge preparation services improves postoperative recovery, discharge readiness, quality of life, and satisfaction with nursing services in patients undergoing lung cancer surgery.
9.Evidence summary of nutritional management of food for special medical purpose in postoperative adjuvant chemotherapy patients with cancer
Chaoyue GAO ; Min LI ; Yinzhu ZHANG ; Peili ZHANG ; Xiaoya HOU ; Yixia CHENG
Chinese Journal of Nursing 2024;59(8):934-941
Objective To summarize the best evidence of nutritional support therapy with food for special medi-cal purpose for patients undergoing adjuvant chemotherapy after oncology surgery,and to provide a reference basis for standardizing the application of food for special medical purpose and guiding clinical nutritional therapy practice for oncology patients.Methods Computer search was conducted on UpToDate,Guidelines International Network(GIN),National Guideline Clearinghouse,National Comprehensive Cancer Network,National Institute for Health and Clinical Excellence,Oncology Nursing Society,American Society for Parenteral Enteral Nutrition,European Society for Clinical Nutrition and Metabolism,Chinese Society for Parenteral and Enteral Nutrition,Joanna Briggs Institute Evidence-Based Health Care Centre database,Cochrane Library,PubMed,CINAHL,Scopus,Web of Science,Em-base,CBM,Wanfang,and China Knowledge Network on the nutritional support treatment of food for special medical purpose for postoperative adjuvant chemotherapy patients.The retrieval period was from January 2012 to August 2022.Quality evaluation of the literature was completed independently by 2 evidence-based trained researchers and combined with expert advice to extract and summarise evidence for the literature that met quality standards.Results A total of 14 articles were included,including 4 guidelines,1 clinical decision,2 systematic re views,4 expert consen-suses,and 3 randomized controlled trials.The 14 pieces of best evidence were compiled,covering 6 aspects of nu-tritional screening and assessment,nutritional education,recommended dose,formulation selection,nutritional treat-ment,and management of adverse effects.Conclusion This study summarises the best evidence on the nutritional management of food for special medical purpose in postoperative adjuvant chemotherapy patients with cancer,which is scientific and systematic.When administering nutritional therapy to patients,healthcare professionals should fully assess the nutritional status of patients,make clear and prudent choices on the dosage and type of food for special medical puipose to be used by patients,and guide patients to improve their nutritional status safely and effectively to improve their quality of life.To improve the quality of life.
10.Expression Level and Clinical Value of dMMR Proteins and miRNA Let-7 in Endometrial Carcinoma Tissue
Yajun ZHANG ; Peili LIU ; Yue JIANG ; Li YAN ; Yunyun CHEN ; Xin JIANG ; Fanfei MENG
Journal of Modern Laboratory Medicine 2024;39(3):48-52,108
Objective To investigate the relationship between the expression level of miRNA Let-7 and the deletion of DNA mismatch repair(dMMR)proteins in endometrial carcinoma(EC).Methods A total of 74 patients with EC who underwent radical surgery at Lianyungang Maternal and Child Health Hospital in Jiangsu Province from May 2016 to December 2022 were selected.Immunohistochemistry was used to detect the expression of dMMR proteins(including MLH1,PMS2,MSH2,and MSH6),while real-time fluorescence quantitative polymerase chain reaction(qRT-PCR)was performed to measure the relative expression levelof miRNA Let-7.According to the expression of dMMR proteins,EC patients were divided into the complete expression group(n=43)and the absent expression group(n=31).Logistic multivariate regression analysis was conducted to identify risk factors associated with dMMR protein deficiency,and receiver operating characteristic(ROC)curve was plotted to evaluate the predictive value of relevant factors.Results In 74 cases of EC,the expression level of miRNA Let-7 was higher in the myographic infiltration<1/2 group than in the myographic infiltration ≥ 1/2 group,and the difference was significant(t=1.79,P=0.04).The deletion rate of dMMR protein expression was 41.89%,the deletion rate in patients aged<55 years and miRNA Let-7 low expression group(<0.715)were higher than those in ≥ 55 years and miRNA Let-7 high expression group(≥ 0.715),with significant differences(x2=3.92,4.50,all P<0.05).Logistic regression analysis revealed that miRNA Let-7 expression level was an independent risk factor for dMMR expression deletion(P=0.012).Spearman correlation analysis demonstrated a negative correlation between miRNA Let-7 expression level and dMMR protein deletion(r=-0.247,P=0.034).ROC curve analysis indicated that the expression level of miRNA Let-7 had a certain predictive value for dMMR protein deletion in EC patients,with an AUC of 0.737,an optimal critical value of 0.77,a sensitivity and a specificity of 0.651 and 0.806,respectively.Conclusion The expression level of miRNA Let-7 was correlated with the deletion of dMMR proteins in patients diagnosed with EC.Moreover,it served as a potential risk factor for dMMR protein deficiency.It may offer valuable insights into predicting dMMR expression deletion.

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