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.Para-aortic lymph node dissection with or without nerve-sparing in gynecological malignancies
Qiang WEN ; Yuyang ZHU ; Haifei ZHOU ; Li YANG ; Feng SHAO ; Tao ZHU ; Zhuyan SHAO
Journal of Gynecologic Oncology 2025;36(1):e9-
Objective:
Para-aortic lymph node dissection (PALND) is a widely used treatment that causes many complications. This study is to evaluate the efficacy and safety of nerve-sparing para-aortic lymph node dissection (NSPALND) by comparing it with conventional PALND in gynecological malignancies and to prove whether locating the superior hypogastric plexus (SHP) can help reveal the para-aortic nerves.
Methods:
This is a retrospective study of the patients who underwent para-aortic lymphadenectomy from January 2020 to December 2022 at Zhejiang Cancer Hospital. All of them were divided into NSPALND and PALND groups according to whether or not nervesparing was performed. The surgical, functional and oncological outcomes were evaluated.
Results:
There were 43 patients enrolled, of which, 20 patients underwent NSPALND and 23 patients underwent PALND. The para-aortic nerves were successfully revealed by locating the SHP in all 20 cases of NSPALND. The post-operative anal exhaust time in the NSPALND group was significantly shorter than that in the PALND group (2.5 vs. 4 days, p=0.006), and the incidence of acute intestinal obstruction in the NSPALND group was significantly lower than that in the PALND group (10% vs. 39%, p=0.029). There was no difference between the two groups in terms of catheterization duration, urinary retention, dysuria, as well as the number of lymph nodes removed and the para-aortic recurrence rate.
Conclusion
NSPALND can significantly reduce the rate of acute intestinal obstruction and improve post-operative intestinal function. Locating the SHP and using it as an anatomical landmark to reveal the para-aortic nerves is feasible. Its exact clinical value needs to be further studied.
3.Para-aortic lymph node dissection with or without nerve-sparing in gynecological malignancies
Qiang WEN ; Yuyang ZHU ; Haifei ZHOU ; Li YANG ; Feng SHAO ; Tao ZHU ; Zhuyan SHAO
Journal of Gynecologic Oncology 2025;36(1):e9-
Objective:
Para-aortic lymph node dissection (PALND) is a widely used treatment that causes many complications. This study is to evaluate the efficacy and safety of nerve-sparing para-aortic lymph node dissection (NSPALND) by comparing it with conventional PALND in gynecological malignancies and to prove whether locating the superior hypogastric plexus (SHP) can help reveal the para-aortic nerves.
Methods:
This is a retrospective study of the patients who underwent para-aortic lymphadenectomy from January 2020 to December 2022 at Zhejiang Cancer Hospital. All of them were divided into NSPALND and PALND groups according to whether or not nervesparing was performed. The surgical, functional and oncological outcomes were evaluated.
Results:
There were 43 patients enrolled, of which, 20 patients underwent NSPALND and 23 patients underwent PALND. The para-aortic nerves were successfully revealed by locating the SHP in all 20 cases of NSPALND. The post-operative anal exhaust time in the NSPALND group was significantly shorter than that in the PALND group (2.5 vs. 4 days, p=0.006), and the incidence of acute intestinal obstruction in the NSPALND group was significantly lower than that in the PALND group (10% vs. 39%, p=0.029). There was no difference between the two groups in terms of catheterization duration, urinary retention, dysuria, as well as the number of lymph nodes removed and the para-aortic recurrence rate.
Conclusion
NSPALND can significantly reduce the rate of acute intestinal obstruction and improve post-operative intestinal function. Locating the SHP and using it as an anatomical landmark to reveal the para-aortic nerves is feasible. Its exact clinical value needs to be further studied.
4.Para-aortic lymph node dissection with or without nerve-sparing in gynecological malignancies
Qiang WEN ; Yuyang ZHU ; Haifei ZHOU ; Li YANG ; Feng SHAO ; Tao ZHU ; Zhuyan SHAO
Journal of Gynecologic Oncology 2025;36(1):e9-
Objective:
Para-aortic lymph node dissection (PALND) is a widely used treatment that causes many complications. This study is to evaluate the efficacy and safety of nerve-sparing para-aortic lymph node dissection (NSPALND) by comparing it with conventional PALND in gynecological malignancies and to prove whether locating the superior hypogastric plexus (SHP) can help reveal the para-aortic nerves.
Methods:
This is a retrospective study of the patients who underwent para-aortic lymphadenectomy from January 2020 to December 2022 at Zhejiang Cancer Hospital. All of them were divided into NSPALND and PALND groups according to whether or not nervesparing was performed. The surgical, functional and oncological outcomes were evaluated.
Results:
There were 43 patients enrolled, of which, 20 patients underwent NSPALND and 23 patients underwent PALND. The para-aortic nerves were successfully revealed by locating the SHP in all 20 cases of NSPALND. The post-operative anal exhaust time in the NSPALND group was significantly shorter than that in the PALND group (2.5 vs. 4 days, p=0.006), and the incidence of acute intestinal obstruction in the NSPALND group was significantly lower than that in the PALND group (10% vs. 39%, p=0.029). There was no difference between the two groups in terms of catheterization duration, urinary retention, dysuria, as well as the number of lymph nodes removed and the para-aortic recurrence rate.
Conclusion
NSPALND can significantly reduce the rate of acute intestinal obstruction and improve post-operative intestinal function. Locating the SHP and using it as an anatomical landmark to reveal the para-aortic nerves is feasible. Its exact clinical value needs to be further studied.
5.Evaluation of the Efficacy of Local Corticosteroid Injection in the Treatment of Idiopathic Granulomatous Mastitis: A Retrospective Cohort Study Based on Clinical Cases
Yanna ZHANG ; Li PENG ; Xinyu REN ; Feng MAO ; Qiang SUN ; Yidong ZHOU
Medical Journal of Peking Union Medical College Hospital 2025;16(5):1214-1220
To compare the clinical efficacy of intralesional corticosteroid injection combined with topical corticosteroids versus topical corticosteroids alone in patients with idiopathic granulomatous mastitis (IGM). Patients diagnosed with IGM and treated at the Breast Surgery Department of Peking Union Medical College Hospital between October 2016 and March 2018 were retrospectively analyzed. Based on treatment modalities, patients were divided into an injection group (receiving intralesional corticosteroid injections plus topical corticosteroids) and a control group (receiving topical corticosteroids alone). Clinical outcomes and recurrence rates were compared between the two groups. Seventy-eight patients meeting the inclusion and exclusion criteria were enrolled, with 51 in the injection group and 27 in the control group. The median age was 35 years (range: 22-45). The maximum lesion diameter was 8.7±2.9 cm in the injection group and 7.1±2.7 cm in the control group. Compared with the control group, the injection group showed a significantly shorter time to half remission(2.8±0.9 weeks Compared with topical corticosteroid monotherapy, the combina-tion of intralesional corticosteroid injection and topical corticosteroids provides faster symptom control and shorter treatment duration while maintaining high efficacy and low long-term recurrence rates, offering a more effective therapeutic option for IGM patients.
6.Relationship between ripretinib concentration and the prognosis of advanced gastrointestinal stromal tumors in China: a multicenter study
Hao XU ; Xiaofeng SUN ; Haoran QIAN ; Ming WANG ; Xin WU ; Ye ZHOU ; Feng WANG ; Luning SUN ; Yongqing WANG ; Fengyuan LI ; Qiang ZHANG ; Zekuan XU
Chinese Journal of Gastrointestinal Surgery 2024;27(11):1133-1140
Objective:To investigate the prognosis and safety of ripretinib in the treatment of patients with advanced gastrointestinal mesenchymal stromal tumors (GISTs) and to analyze the relationship between blood concentrations of this drug and prognosis.Methods:In this retrospective study, we investigated the effects of ripretinib in patients with advanced GISTs. The inclusion criteria comprised: (1) daily oral administration of ripretinib scheduled; and (2) uninterrupted treatment for at least 1month, with a stable and relatively fixed daily dosage maintained for a minimum of 2 weeks. Exclusion criteria comprised concurrent use of other tyrosine kinase inhibitors and presence of significant organ dysfunction. We retrospectively identified 79 patients with advanced GISTs who had received ripretinib across seven medical centers, namely Jiangsu Provincial Hospital, Jiangsu Cancer Hospital, Nanjing Drum Tower Hospital Affiliated to Nanjing University, Sir Run Run Shaw Hospital of Zhejiang University, Renji Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, and the General Hospital of the People's Liberation Army, from 1 June 2021 to 31 March 2024. The cohort included 48 men and 31 women, 19 of whom had received ripretinib as second-line, 13 as third-line, and 47 as fourth-line therapy. Two peripheral venous blood samples were obtained from each participant and high-performance liquid chromatography-tandem mass spectrometry used to determine peak (Cmax) and trough (Cmin) concentrations of ripretinib. Machine learning methodologies, specifically the K-nearest neighbor algorithm combined with the Gridsearch CV strategy, were employed to establish the threshold for Cmin. We analyzed adverse reactions, treatment efficacy, median progression-free survival (mPFS), and the relationship between drug blood concentration and selected clinical parameters.Results:In the entire cohort, the Cmin and Cmax of ripretinib were 467 ± 360 μg/L and 986 ± 493 μg/L, respectively. Notably, female patients and individuals in the high-dose group exhibited significantly higher values for both Cmin and Cmax (both P<0.05). However, variations in drug concentrations associated with the line of ripretinib therapy, treatment efficacy, disease progression, and presence of selected specific genetic mutations were not significantly associated with values of Cmin and Cmax ( P>0.05). Among the 79 patients with advanced GISTs receiving ripretinib, reported adverse reactions included alopecia (53, 67.09%), hand–foot syndrome (24, 30.38%), fatigue (22, 27.85%), and myalgia (21, 26.58%). Two patients (2.53%) had grade III complications, both classified as hand–foot syndrome. The correlation between Cmax and adverse reactions was not statistically significant ( P > 0.05). By the time of the latest follow-up, five deaths (6.3%) had occurred within the cohort. The mPFS for the group was 16.3 months, with a mPFS of 14.4 months for those receiving standard dosage and 7.0 months for those receiving escalating dosage. Among the 65 patients treated with standard doses of ripretinib, those with Cmin exceeding a threshold of 450 μg/L exhibited a significantly longer mPFS (18.0 months vs.13.7 months; P < 0.05). Conclusion:In China, patients with advanced GISTs exhibit a notable tolerance to ripretinib, with no evidence for a correlation between adverse reactions and Cmax for the drug. Additionally, a Cmin exceeding 450 μg/L may be associated with an extended mPFS.
7.Developing Syllabus for Rare Breast Diseases Using the Integrated Multimodality of Case-/Problem-/Resource-Based Learning
Ru YAO ; Jiahui ZHANG ; Jie LIAN ; Yang QU ; Xinyue ZHANG ; Xin HUANG ; Lu GAO ; Jun ZHAO ; Li HUANG ; Yingzi JIANG ; Linzhi LUO ; Songjie SHEN ; Feng MAO ; Qiang SUN ; Bo PAN ; Yidong ZHOU
JOURNAL OF RARE DISEASES 2024;3(3):391-399
Objective This study aims at establishing a teaching catalog and content for breast rare dis-eases and developing the syllabus for the breast rare disease using integrated multimodality of case-/problem-/resource-based learning(CBL+PBL+RBL).Methods By conducting bibliometrics co-occurrence analysis,we collected 6291 articles on breast rare disease published from January,1975 to June,2024.Additionally,we re-trieved the Textbook on Rare Diseases,the Catalog of Chinese Rare Disease,and Second Batch of Rare Dis-ease Catalog and then decided the teaching content.Results From 16,387 keywords,1000(6.1%)keywords were identified through co-occurrence analysis,including 50(0.3%)candidate diseases.These were classified into three categories:rare primary breast diseases,rare genetic mutation-related diseases associated with breast cancer,and rare systemic multi-system diseases involving the breast.From the candidate list,20(0.1%)rare primary breast diseases were further selected for their notable clinical teaching significance,and significant multi-systemic diseases affecting the breast,whether related to gene mutations or not.Teaching plans were draf-ted using a diversified parallel teaching approaches,taking into account the characteristics of different diseases and the focus of different teaching methods.Conclusions This study initiated the development of the teaching content for breast rare diseases and developed the teaching syllabus using the CBL+PBL+RBL integrated multi teaching model and targeting each rare breast disease for the critical point for teaching.
8.Clinical characteristics analysis of primary pancreatic lymphoma
Yinghao SUN ; Jianing LI ; Kun HE ; Liang ZHU ; Yunlu FENG ; Qiang WANG ; Qingwei JIANG ; Yan ZHANG ; Qiang XU ; Zheng WANG ; Jingya ZHOU ; Dong WU
Chinese Journal of Pancreatology 2024;24(1):52-56
Objective:To analyze clinical characteristics of primary pancreatic lymphoma (PPL) patients.Methods:Clinical features of 22 patients diagnosed as PPL admitted to Peking Union Medical College Hospital from January 2002 to May 2023 were analyzed retrospectively.Results:The median age was 56.4±13.3 years. The median time from onset to diagnosis was 1.0 (1.0, 3.0) months. The main clinical manifestations were abdominal pain (15/22), weight loss (14/22) and jaundice (10/22). Elevated lactate dehydrogenase (LDH) was observed in 15/20 (75%) patients. Only 2 (2/9, 22.2%) patients had increased CA199 levels and 2 (2/9, 22.2%) patients had increased CEA levels. The maximum tumor diameter was 5.0 (3.8, 6.9) cm. Contrast-enhanced CT mostly showed low enhancement lesions. Major pancreatic duct dilatation were rare on CT scan (4/20). Fifteen patients were confirmed by pancreatic pathology, of which 8 were obtained by surgery, 4 were obtained by CT or ultrasound-guided percutaneous biopsy, and 3 were obtained by EUS-FNA. The main pathological type was diffuse large B-cell lymphoma (14/22). 19 patients received chemotherapy, and 6 patients died with a median follow-up of 5.0 (1.5, 35.5) months.Conclusions:PPL is rare and easy to be misdiagnosed. Elevated LDH levels, normal tumor markers, and non-dilatation of main pancreatic duct are important diagnostic clues. It is important to obtain pathology by EUS-FNA and other methods for definite diagnosis.
9.New advances in stroke and cerebral embolism protection devices in transcatheter aortic valve replacement
Yun-Feng LI ; Shi-Qiang ZHOU ; Xi-De SHI ; Fei LI
Chinese Journal of Interventional Cardiology 2024;32(1):51-57
Stroke is one of the most serious complications of transcatheter aortic valve replacement(TAVR),tremendously increasing mortality and the loss of neurocognitive function.Since TAVR is expected to further spread into lower-risk patient groups,there will be greater emphasis to obviate such serious complications.One possible technique for preventing stroke is using cerebral embolic protection devices(CEPDs).CEPDs are designed for capturing or deflecting emboli that are enter route to the brain and hence to protect the brain from embolism.Since this is a rapidly growing field with recent advances,and the impact of CEPD on preventing neurological events is still limited,there is an urgent need for understanding the role of CEPD in preventing clinically significant strokes.Although their clinical utilization is increasing,the risk factors for stroke related to TAVR and evidence for using CEPDs are not yet clear.In this review,we present an overview of the available literature on TAVR related stroke and CEPD,and outline recent advances within this field.
10.Emergency single drainage tube and dual target thalamic hematoma ventricular drainage surgery based on body surface marker localization for the treatment of thalamic hemorrhage breaking into the ventricle with hydrocephalus
Baoming JIA ; Jiankai ZHAO ; Lizhen WANG ; Xiguang ZHOU ; Hongsha PEI ; Yanli ZHANG ; Guo-Qiang FENG ; Hongbin KU
Chinese Journal of Nervous and Mental Diseases 2024;50(1):23-29
Objective To explore the application value of emergency temporal body surface positioning for single drain dual-target thalamic hematoma ventricular drainage in the treatment of thalamic hemorrhage breaking into ventricle with hydrocephalus.Methods A retrospective analysis was conducted on 223 patients with thalamic hemorrhage breaking into the ventricles with hydrocephalus,including a study group of 115 cases who underwent emergency single drain dual-target thalamic hematoma ventricular drainage surgery with temporal body surface positioning,and a control group of 108 cases who underwent emergency ventricular drainage first and then underwent stereotactic thalamic hematoma drainage surgery after the condition stabilized.Compare the differences in postoperative complications and treatment outcomes between two groups of patients,and evaluate the application value of temporal surface positioning for single drain dual-target thalamic hematoma ventricular drainage surgery in the treatment of thalamic hemorrhage breaking into the ventricle with hydrocephalus.Results The postoperative rebleeding rates,hematoma clearance and death were 5.2%,87.5%±7.3%and 13.9%in the study group and 4.7%,90.2%±8.5%and 15.7%in control group,respectively.There was no significant difference between the two groups(P>0.05).The tube time,postoperative intracranial infection,Shunt dependent hydrocephalus,effective treatment and favorable prognosis of and the control group were(75.5±18.4)h,3.5%,19.1%,53.9%and 51.3%in the study group and(130.8±22.9)h,13.9%,35.1%,38.7%and 38.0%,respectively.The difference between the two groups was statistically significant(P<0.05).Conclusion Body surface landmark-guided emergency single drain dual-target thalamic hematoma ventricular drainage surgery for the treatment of thalamic hemorrhage breaking into the ventricle with hydrocephalus is safe and reliable,and can improve the patient's prognosis.

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