1.The Ferroptosis-inducing Compounds in Triple Negative Breast Cancer
Xin-Die WANG ; Da-Li FENG ; Xiang CUI ; Su ZHOU ; Peng-Fei ZHANG ; Zhi-Qiang GAO ; Li-Li ZOU ; Jun WANG
Progress in Biochemistry and Biophysics 2025;52(4):804-819
Ferroptosis, a programmed cell death modality discovered and defined in the last decade, is primarily induced by iron-dependent lipid peroxidation. At present, it has been found that ferroptosis is involved in various physiological functions such as immune regulation, growth and development, aging, and tumor suppression. Especially its role in tumor biology has attracted extensive attention and research. Breast cancer is one of the most common female tumors, characterized by high heterogeneity and complex genetic background. Triple negative breast cancer (TNBC) is a special type of breast cancer, which lacks conventional breast cancer treatment targets and is prone to drug resistance to existing chemotherapy drugs and has a low cure rate after progression and metastasis. There is an urgent need to find new targets or develop new drugs. With the increase of studies on promoting ferroptosis in breast cancer, it has gradually attracted attention as a treatment strategy for breast cancer. Some studies have found that certain compounds and natural products can act on TNBC, promote their ferroptosis, inhibit cancer cells proliferation, enhance sensitivity to radiotherapy, and improve resistance to chemotherapy drugs. To promote the study of ferroptosis in TNBC, this article summarized and reviewed the compounds and natural products that induce ferroptosis in TNBC and their mechanisms of action. We started with the exploration of the pathways of ferroptosis, with particular attention to the System Xc--cystine-GPX4 pathway and iron metabolism. Then, a series of compounds, including sulfasalazine (SAS), metformin, and statins, were described in terms of how they interact with cells to deplete glutathione (GSH), thereby inhibiting the activity of glutathione peroxidase 4 (GPX4) and preventing the production of lipid peroxidases. The disruption of the cellular defense against oxidative stress ultimately results in the death of TNBC cells. We have also our focus to the realm of natural products, exploring the therapeutic potential of traditional Chinese medicine extracts for TNBC. These herbal extracts exhibit multi-target effects and good safety, and have shown promising capabilities in inducing ferroptosis in TNBC cells. We believe that further exploration and characterization of these natural compounds could lead to the development of a new generation of cancer therapeutics. In addition to traditional chemotherapy, we discussed the role of drug delivery systems in enhancing the efficacy and reducing the toxicity of ferroptosis inducers. Nanoparticles such as exosomes and metal-organic frameworks (MOFs) can improve the solubility and bioavailability of these compounds, thereby expanding their therapeutic potential while minimizing systemic side effects. Although preclinical data on ferroptosis inducers are relatively robust, their translation into clinical practice remains in its early stages. We also emphasize the urgent need for more in-depth and comprehensive research to understand the complex mechanisms of ferroptosis in TNBC. This is crucial for the rational design and development of clinical trials, as well as for leveraging ferroptosis to improve patient outcomes. Hoping the above summarize and review could provide references for the research and development of lead compounds for the treatment for TNBC.
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.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.
4.Preliminary exploration of the application of the DeepSeek-V3-0324 large-scale model in medication education in pharmaceutical outpatient clinics
Fengdan QIAN ; Tingting JIA ; Die ZHANG ; Lichao ZHANG ; Ya XUE
China Pharmacy 2025;36(17):2192-2196
OBJECTIVE To explore a new model of intelligent medication education for pharmaceutical outpatient clinics by constructing dynamic HTML web pages through the DeepSeek-V3-0324 large-scale model. METHODS Clinical pharmacists integrated key clinical information such as patients’ basic information, medication history and medication precautions in real time, and generated a standardized medication education list through the DeepSeek-V3-0324 large-scale model and manual review. RESULTS The DeepSeek-V3-0324 large-scale model was applied in the pharmaceutical outpatient clinics to generate a personalized medication education list, which could effectively solve the disunity of pharmacy guidance caused by the lack of standardization of medication education and the difference of individualized experience of pharmacists in the traditional pharmaceutical outpatient clinics in the face of complex cases, and medication errors caused by forgetting or misremembering information among certain special patient populations after receiving medication education. CONCLUSIONS The transformation and application of artificial intelligence technology in pharmaceutical outpatient clinics is an innovation of pharmaceutical outpatient service means, which can provide patients with immediate and personalized medication education and improve the quality of pharmaceutical care. However, it is also necessary to face the lag of database update and the lack of risk management, as well as the lack of diversification of medication education lists.
5.The role of brevican regulation in the antidepressant effects of electroacupuncture in a chronic stress rat model
Cong Gai ; Zhenyu Guo ; Kai Guo ; Shixin Yang ; Yi Zhang ; Huimin Zhu ; Feifei Kan ; Hongmei Sun ; Die Hu
Journal of Traditional Chinese Medical Sciences 2024;11(4):513-521
Objective:
To investigate the mechanism of electroacupuncture (EA) for treating depression and to explore the role of brevican in the medial prefrontal cortex (mPFC) in modulating stress susceptibility and the antidepressant effects of EA in rats.
Methods:
Twenty-four Sprague–Dawley (SD) rats were equally divided into three groups: green fluorescent protein (GFP) + control, GFP + chronic unpredicted mild stress (CUMS), and short-hairpin RNA targeting on brevican (shBcan) + CUMS. Another 24 SD rats were equally divided into CUMS + GFP, CUMS + GFP + EA, and CUMS + shBcan + EA groups. Behavioral tests were conducted to assess depression-like behavior. Western blot analysis was used to evaluate the expression of brevican, aggrecan, GLuA1, and PSD95 in mPFC subregions.
Results:
Behavioral parameter evaluation show that rats in the shBcan + CUMS group exhibited a significantly reduced sucrose preference (P = .0002) and increased immobility time (P = .0011) compared to those in rats in the GFP + CUMS group. Western blotting showed that brevican expression was significantly downregulated in the PrL of the shBcan + CUMS group compared with that in the GFP + CUMS group (P = .0192). Furthermore, compared to the CUMS + GFP + EA group, the CUMS + shBcan + EA group exhibited a significantly decreased sucrose preference (P = .0334), increased immobility time (P = .0465), and increased latency to food (P = .0261). In the CUMS + shBcan + EA group, the EA-induced brevican and PSD95 overexpression was reversed, compared with that in the CUMS + GFP + EA group (P = .0454 and P = .0198, respectively).
Conclusion
EA exerts its antidepressant effects through the modulation of brevican expression in rats. Our findings highlight the important role for brevican in stress susceptibility, which could be a potential target for treating depression.
6.Effect of Buyang Huanwutang in Treating Diabetic Peripheral Neuropathy by Inhibiting Pyroptosis Through AMPK/ULK1 Mitophagy Pathway
Jingwen AN ; Linchun SONG ; Die CHEN ; Wang ZHANG ; Jiaxin TIAN ; Tianya ZHANG ; Ying BEN
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(15):1-10
ObjectiveTo observe the effect of Buyang Huanwutang in treating diabetic peripheral neuropathy (DPN) by inhibiting pyroptosis through AMP-activated protein kinase (AMPK)/UNC-51-like kinase 1 (ULK1) mitophagy pathway. MethodSixty male SPF SD rats (6-7 weeks old) were used in animal experiments and numbered according to their body mass. They were then randomly divided into four groups by computer: normal group, model group, α-lipoic acid group(60 mg·kg-1), and Buyang Huanwutang group(15 g·kg-1), with 15 rats in each group. The diabetic model was established by injection of streptozocin (STZ). After successful modeling, the α-lipoic acid group and the Buyang Huanwutang group were given corresponding drugs, and the normal group and the model group were given normal saline. Sensory nerve conduction velocity (SNCV) and paw withdrawal threshold (PWT) were measured at the end of administration for 12 weeks. Immunohistochemistry and Western blot were used to detect the expression of phosphorylated AMP activated protein kinase (p-AMPK), phosphorylated UNC-51-like kinase 1 (p-ULK1), protein involved in microtubule-associated protein 1 light chain 3 (LC3), selective autophagy receptors (p62/SQSTM1), Beclin1, NOD receptor protein structure domain-related proteins 3 (NLRP3), Caspase-1 (Caspase-1), and interleukin-1 beta (IL-1β) in dorsal root ganglia (DRG). Immunofluorescence was used to detect the expression of the N-terminal gasdermin D (N-GSDMD). ResultCompared with those in the normal group, rats in the model group had increased fasting blood glucose (P<0.01) and significantly reduced SNCV, PWT (P<0.01), LC3Ⅱ/LC3Ⅰ, Beclin1, p-AMPK/AMPK, and p-ULK1/ULK1 (P<0.01). In addition, p62, NLRP3, N-GSDMD/GSDMD, IL-1β, and cleaved Caspase-1/Caspase-1 were significantly increased (P<0.01). Compared with those in the model group, SNCV and PWT were increased (P<0.01) in each administration group, and LC3Ⅱ/LC3Ⅰ, Beclin1, p-AMPK/AMPK, and p-ULK1/ULK1 were significantly increased (P<0.05, P<0.01). p62, N-GSDMD/GSDMD, cleaved Caspase-1/Caspase-1, NLRP3, and IL-1β decreased (P<0.05, P<0.01). Compared with the α-lipoic acid group, the Buyang Huanwutang group had significantly increased SNCV, PWT (P<0.05), LC3Ⅱ/LC3Ⅰ, and p-ULK1/ULK1 (P<0.05) and significantly decreased NLRP3 and N-GSDMD/GSDMD (P<0.05). ConclusionBuyang Huanwutang regulates mitophagy and inhibits pyroptosis through the AMPK/ULK1 pathway to prevent and treat DPN, and its therapeutic effect may be better than α-lipoic acid.
7.Effects of electroacupuncture on motor function and related molecular mechanisms in mice with Parkinson's disease
Ling QI ; Yanan LI ; Yao WANG ; Xiaolei ZHANG ; Mengni HU ; Hanzhang LI ; Die XIAO ; Zhen RONG ; Jun MA
Journal of Beijing University of Traditional Chinese Medicine 2024;47(5):721-728
Objective To explore the effects of electroacupuncture on motor function in Parkinson's disease(PD)model mice and NLRP3 inflammasome-related proteins in the midbrain substantia nigra(SN).Methods C57BL/6 mice were assigned to three groups according to the random number table method:control group,model group,and electroacupuncture(EA)group,12 mice per group.The PD model was reproduced by intragastric administration of rotenone solution 10 mg/(kg·d).EA group was administered at the three selected points,"Fengfu"(GV16),"Taichong"(LR3),and"Zusanli"(ST36),with a treatment cycle of 2 weeks.The control and model groups took the same time synchronous fixation operation for the control variable.Behavioral scores and open field tests were used to detect the exercise ability of mice in each group.Tyrosine hydroxylase(TH)and α-synuclein(α-syn)in the midbrain SN of mice in all groups were measured with an immunohistochemistry test.NLRP3 and cysteinyl aspartate specific proteinase-1(Caspase-1)protein expression levels in the midbrain SN of mice in the three groups were measured using Western blotting,and interleukin-1β(IL-1β)content was determined with an enzyme-linked immunosorbent assay.Results Compared to the control group,the behavioral scores of the mice in the model group were higher(P<0.01).Compared to the model group,the behavioral scores of the mice in the EA group were lower(P<0.01).Compared to the control group,the time ratio of the relative rest state of the mice in the model group(<100 mm/s)increased significantly(P<0.01),while the time ratio of the slow motion(100~200 mm/s)and time ratio of the fast motion(>200 mm/s)state decreased significantly(P<0.01).Compared to the model group,the time ratio spent in the relative rest state of mice in the EA group decreased significantly(P<0.01),while the time ratio of the slow motion state and time ratio of the fast motion state and movement rate increased significantly(P<0.01).Compared to the control group,the TH expression level decreased in the SN in the model group(P<0.01),while α-syn increased(P<0.01).Compared to the model group,the TH expression level in the EA group increased(P<0.05),while α-syn decreased(P<0.05).Compared to the control group,the protein expressions of NLRP3 and Caspase-1 in the SN of the model group increased(P<0.01);compared to the model group,the expressions of NLRP3 and Caspase-1 in the SN of the midbrain of mice decreased after EA treatment(P<0.01).Compared to the control group,IL-1β in the SN of the mouse midbrain increased in the model group(P<0.01).Compared to the model group,IL-1β decreased in the EA group(P<0.05).Conclusion This experiment shows that stimulation of EA in"Fengfu","Taichong",and"Zusanli"can effectively reduce abnormal aggregation of the PD marker α-syn,increase TH expression,and enhance the motor dysfunction of PD model mice.The molecular mechanism is related to the regulation of the expression of NLRP3,Caspase-1,and IL-1β of inflammasome-related pathways.
8.Current situation and influencing factors of wheezing among children and adolescents aged 3-18 years in 11 cities in China from 2022 to 2023
Qin HUI ; Qi SUN ; Jing LIU ; Fang YE ; Die LIU ; Yuanmei CHEN ; Jie CHEN ; Qi ZHANG
Chinese Journal of Preventive Medicine 2024;58(6):869-874
Objective:To explore the incidence and influencing factors of wheezing among children and adolescents aged 3-18 years in 11 cities in China from 2022 to 2023.Methods:From October 2022 to August 2023, 11 cities including Xishuangbanna in Yunnan Province, Suqian in Jiangsu Province, Chifeng and Hohhot in Inner Mongolia, Tangshan in Hebei Province, Changzhi in Shanxi Province, Yinchuan in Ningxia Province, Lanzhou and Dingxi in Gansu Province, Linyi in Shandong Province, and Tonghua in Jilin Province were selected as research sites to recruit kindergarten children and primary and secondary school adolescents in local urban areas. A total of 21 959 children and adolescents were included in this study. Demographic information, wheezing data (whether wheezing has occurred in the past and whether wheezing attacks have occurred in the past one year), personal history, family history and other information were collected through questionnaires. The multivariate logistic regression model was used to analyze the influencing factors of wheezing attacks in the past one year.Results:The mean age of 21 959 children and adolescents was (12.09±3.65) years old, and 52.3% (11 480) were boys. The incidence of wheezing history was 3.7% (816 cases), and the incidence of wheezing attacks in the past year was 2.5% (556 cases). The multivariate logistic regression model analysis results showed that compared with older age, girls, full-term natural delivery, no allergic rhinitis, no family history of allergic diseases, no passive smoking, partial diet, natural conception and childbirth, the children aged 3-18 years with young age, male, partial diet, passive smoking, family history of allergic diseases, allergic rhinitis, cesarean section, premature birth, and assisted reproduction had a higher risk of wheezing [ OR (95% CI): 0.86(0.84-0.88), 1.27(1.07-1.51), 2.31(1.95-2.75), 2.09(1.76-2.47), 3.5(2.80-4.37), 4.05(3.39-4.83), 1.20(1.02-1.43), 2.26(1.66-3.09), and 1.67(1.01-2.78)]. Conclusion:From 2022 to 2023, the incidence of wheezing among children aged 3-18 years in China is not significantly higher than before, and childhood wheezing may be related to factors such as children′s age, gender, dietary habits, family and personal history of allergic diseases, passive smoking, and perinatal period.
9.Influence of peripheral blood NLR,MLR and PLR in prognosis of patients with multiple myeloma
Xinlan XIA ; Die LIU ; Lihong AN ; Yan LI ; Peng ZHAO ; Yan ZHANG ; Mengxing LI ; Jishi WANG ; Yinghao LU
Chongqing Medicine 2024;53(15):2261-2268
Objective To investigate the influence of peripheral blood neutrophil-to-lymphocyte ratio (NLR),monocyte-to-lymphocyte ratio (MLR) and platelet-to-lymphocyte ratio (PLR) on the prognosis in the patients with multiple myeloma (MM).Methods A total of 159 newly diagnosed MM admitted and treated in the Affiliated Hospital of Guizhou Medical University from January 2019 to May 2023 were selected as the study subjects.The general clinical data,blood biochemical and marrow routine detection results before the in-itial treatment were collected.NLR,MLR and PLR were calculated.The univariate and multivariate Cox-re-gression model was adopted to analyze the influencing factors.The receiver operating characteristic (ROC) curve was used to analyze the predictive value.The Kaplan-Meier survival curve and Log-Rank test were used to conduct the survival analysis.Results The ROC curve showed that the critical values of NLR,MLR and PLR were 2.682,0.317 and 147.786 respectively.The patients were divided into the high/low NLR groups (n=61,n=98),high/low MLR group (n=76,n=83) and high/low PLR groups (n=59,n=100).The pro-portions of blood calcium<2.5 mmol/L and creatinine<177 μmmol/L in the low NLR group in the low NLR group were higher compared with the high NLR group (P<0.05);the blood calcium,creatinine and DS stage had statistical differences between the low MLR group and high MLR group (P<0.05);blood calcium had statistical difference between the low PLR group and high PLR group (P<0.05).After 3 treatment courses,the complete remission rate in the high NLR group,high MLR group and high PLR group was significantly lower than that in the corresponding low group (P<0.05).The multivariate Cox-regression analysis results showed that hemoglobin<100 g/L and high PLR were the independent risk factors affecting the progress free survival (PFS) stage in the patients with MM (P<0.05).The age>60 years old was the independent risk factors affecting the overall survival (OS) in the patients with MM (P<0.05).Conclusion NLR,MLR and PLR could serve as the assisted tool to evaluate the prognosis in the patients with MM.
10.Mid-term analysis of prospective cohort study of rivaroxaban in preventing CRT in breast cancer
Die SANG ; Shanmin FAN ; Shiyu LI ; Jintao ZHANG ; Hengmin WANG ; Xiaohui ZHAO ; Lijun ZHENG ; Ping LIANG ; Guangbiao XI ; Longmei ZHAO ; Yurong ZHANG ; Peng YUAN
Chinese Journal of Oncology 2024;46(3):256-262
Objective:To explore the efficacy and safety of Rivaroxaban in preventing catheter related thrombosis (CRT) in patients with breast cancer who are undergoing central venous catheter chemotherapy, and provide basis for making standardized prevention and treatment strategies.Methods:In this research, a prospective cohort study was adopted, and breast cancer patients who received central venous catheter chemotherapy in Sanhuan Cancer Hospital during September 2020 to March 2022 were selected as a treatment group to take the rivaroxaban anticoagulation therapy with 10 mg.po.qd for one month. The control group got no preventive anticoagulation therapy. Vascular ultrasound examination was taken to confirm the occurrence of CRT, and a chi-square test was done for comparison the disparity between the groups. Logistic regression was applied to analyze the univariate and multivariate factors for the formation of CRT.Results:In the research, a total of 235 patients were selected, and there were a total of 19 035 days of catheterization with 81 days of catheterization on average. While in the control group, the incidence of CRT was 28.0% (33/118), the incidence of CRT in the treatment group was 20.5% (24/117), the difference was no significant ( P=0.183). Subgroup analysis results showed that the peripherally inserted central catheter (PICC) was performed in 165 cases with the CRT incidence of 18.2% (30/165) and thrombosis was mostly seen around axillary vein, accounting for 63.3%. Subclavian vein catheterization was performed in 63 cases with the CRT incidence of 39.7% (25/63), and thrombosis was mostly seen around subclavian vein, accounting for 88.0% (22/25). Implantable venous access port was implanted in 7 cases around subclavian vein and internal jugular vein with the CRT incidence of 28.6% (2/7). The patients who developed CRT within 30 days after catheterization accounted for 54.4% (31/57), 22.8% (13/57) in a period during 30 days and 60 days) and 22.8% (13/57) in a period during 60 days and 180 days). The diagnosed CRT patients had been treated with rivaroxaban 15 mg.bid.po for 3 months. During the 3 months, 100.0% of the thrombosis waned, 71.9% (41/57) of the thrombosis waned within 30 days, 19.3% (11/57) in a period during 30 and 60days and 8.8% (5/57) in a period during 60 days and 90 days. Univariate and multivariate analysis indicated that the risk of CRT in subclavian vein catheterization was higher than that in PICC, respectively ( OR=2.898, 95% CI:1.386-6.056 P=0.005), and the type of catheterization was an independent factor for the formation of thrombosis. Safety analysis result showed that in the prevention of CRT, rivaroxaban treatment did not induce drug-related bleeding, liver function damage, bone marrow suppression or any other side effects. While CRT diagnosed patients were treated with anticoagulation, they kept the central venous catheter, and the infusion was smooth. These patients all finished the anti-tumor treatment as planned, and no abnormalities like new thrombosis or pulmonary embolism were observed. Conclusions:In the mid-term analysis, the proportion of Rivaroxaban in preventing anticoagulant CRT decreases, but it don't reach statistical significance. The sample size should be further increased for observation. Rivaroxaban is proved effective and very safe in the treatment of CRT, and does not affect the concurrent chemotherapy. Medical personnel should carry out the policy of "early prevention, early detection and early treatment" for CRT so as to improve the patients' quality of life.


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