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.
2.2,3,5,4′-tetrahydroxyldiphenylethylene-2-O-glucoside Attenuates Cerebral Ischemia-reperfusion Injury via PINK1/LETM1 Signaling Pathway
Hongyu ZENG ; Kaimei TAN ; Feng QIU ; Yun XIANG ; Ziyang ZHOU ; Dahua WU ; Chang LEI ; Hongqing ZHAO ; Yuhong WANG ; Xiuli ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(11):145-154
ObjectiveTo investigate the mechanism by which 2,3,5,4'-tetrahydroxyldiphenylethylene-2-O-glucoside (THSG) mitigates cerebral ischemia/reperfusion (CI/R) injury by regulating mitochondrial calcium overload and promoting mitophagy. MethodsSixty male SD rats were randomized into sham, model, SAS (40 mg·kg-1), and low-, medium- and high-dose (10, 20, 40 mg·kg-1, respectively) THSG groups, with 10 rats in each group. The middle cerebral artery occlusion/reperfusion (MCAO/R) model was established by the modified Longa suture method. An oxygen-glucose deprivation/reoxygenation (OGD/R) model was constructed in PC12 cells. Neurological deficits were assessed via Zea Longa scoring, and cerebral infarct volume was measured by 2,3,5-triphenyltetrazolium chloride (TTC) staining. Structural and functional changes of cortical neurons in MCAO/R rats were assessed by hematoxylin-eosin and Nissl staining. PC12 cell viability was detected by cell counting kit-8 (CCK-8) assay, and mitochondrial calcium levels were quantified by Rhod-2 AM. Immunofluorescence was used to detect co-localization of PTEN-induced kinase 1 (PINK1) and leucine zipper/EF-hand-containing transmembrane protein 1 (LETM1) in neurons. Transmission electron microscopy (TEM) was employed to observe mitochondrial morphology in neurons. Western blot was employed to analyze the expression of translocase of outer mitochondrial membrane 20 (TOMM20), autophagy-associated protein p62, microtubule-associated protein light chain 3 (LC3), cysteinyl aspartate-specific proteinase-9 (Caspase-9), B-cell lymphoma 2-associated protein X (Bax), and cytochrome C (Cyt C). ResultsCompared with the sham group, the model group exhibited increased infarct volume (P<0.01) and neurological deficit scores (P<0.01), neuronal structure was disrupted with reduced Nissl bodies. (P<0.01), mitochondrial swelling/fragmentation, decreased PINK1/LETM1 co-localization (P<0.01), upregulated protein levels of LC3Ⅱ/LC3Ⅰ, TOMM20, Caspase-9, Bax, and Cyt C (P<0.01), downregulated protein level of p62 (P<0.05), weakened PC12 viability (P<0.01), and elevated mitochondrial calcium level (P<0.01). Compared with the model group, THSG and SAS groups showed reduced infarct volumes (P<0.05,P<0.01) and neurological deficit scores (P<0.05,P<0.01), mitigated mitochondrial damage, and increased PINK1/LETM1 co-localization (P<0.01). Medium/high-dose THSG and SAS alleviated the neurological damage, increased Nissl bodies (P<0.05,P<0.01), downregulated the protein levels of p62, TOMM20, Caspase-9, Bax, and Cyt C (P<0.05,P<0.01), and elevated the LC3Ⅱ/LC3Ⅰ level (P<0.05,P<0.01). High-dose THSG enhanced PC12 cell viability (P<0.01), increased PINK1/LETM1 co-localization (P<0.01), and reduced mitochondrial calcium (P<0.01). ConclusionTHSG may exert the neuroprotective effect on CI/R injury by activating the PINK1-LETM1 signaling pathway, reducing the mitochondrial calcium overload, and promoting mitophagy.
3.2,3,5,4′-tetrahydroxyldiphenylethylene-2-O-glucoside Attenuates Cerebral Ischemia-reperfusion Injury via PINK1/LETM1 Signaling Pathway
Hongyu ZENG ; Kaimei TAN ; Feng QIU ; Yun XIANG ; Ziyang ZHOU ; Dahua WU ; Chang LEI ; Hongqing ZHAO ; Yuhong WANG ; Xiuli ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(11):145-154
ObjectiveTo investigate the mechanism by which 2,3,5,4'-tetrahydroxyldiphenylethylene-2-O-glucoside (THSG) mitigates cerebral ischemia/reperfusion (CI/R) injury by regulating mitochondrial calcium overload and promoting mitophagy. MethodsSixty male SD rats were randomized into sham, model, SAS (40 mg·kg-1), and low-, medium- and high-dose (10, 20, 40 mg·kg-1, respectively) THSG groups, with 10 rats in each group. The middle cerebral artery occlusion/reperfusion (MCAO/R) model was established by the modified Longa suture method. An oxygen-glucose deprivation/reoxygenation (OGD/R) model was constructed in PC12 cells. Neurological deficits were assessed via Zea Longa scoring, and cerebral infarct volume was measured by 2,3,5-triphenyltetrazolium chloride (TTC) staining. Structural and functional changes of cortical neurons in MCAO/R rats were assessed by hematoxylin-eosin and Nissl staining. PC12 cell viability was detected by cell counting kit-8 (CCK-8) assay, and mitochondrial calcium levels were quantified by Rhod-2 AM. Immunofluorescence was used to detect co-localization of PTEN-induced kinase 1 (PINK1) and leucine zipper/EF-hand-containing transmembrane protein 1 (LETM1) in neurons. Transmission electron microscopy (TEM) was employed to observe mitochondrial morphology in neurons. Western blot was employed to analyze the expression of translocase of outer mitochondrial membrane 20 (TOMM20), autophagy-associated protein p62, microtubule-associated protein light chain 3 (LC3), cysteinyl aspartate-specific proteinase-9 (Caspase-9), B-cell lymphoma 2-associated protein X (Bax), and cytochrome C (Cyt C). ResultsCompared with the sham group, the model group exhibited increased infarct volume (P<0.01) and neurological deficit scores (P<0.01), neuronal structure was disrupted with reduced Nissl bodies. (P<0.01), mitochondrial swelling/fragmentation, decreased PINK1/LETM1 co-localization (P<0.01), upregulated protein levels of LC3Ⅱ/LC3Ⅰ, TOMM20, Caspase-9, Bax, and Cyt C (P<0.01), downregulated protein level of p62 (P<0.05), weakened PC12 viability (P<0.01), and elevated mitochondrial calcium level (P<0.01). Compared with the model group, THSG and SAS groups showed reduced infarct volumes (P<0.05,P<0.01) and neurological deficit scores (P<0.05,P<0.01), mitigated mitochondrial damage, and increased PINK1/LETM1 co-localization (P<0.01). Medium/high-dose THSG and SAS alleviated the neurological damage, increased Nissl bodies (P<0.05,P<0.01), downregulated the protein levels of p62, TOMM20, Caspase-9, Bax, and Cyt C (P<0.05,P<0.01), and elevated the LC3Ⅱ/LC3Ⅰ level (P<0.05,P<0.01). High-dose THSG enhanced PC12 cell viability (P<0.01), increased PINK1/LETM1 co-localization (P<0.01), and reduced mitochondrial calcium (P<0.01). ConclusionTHSG may exert the neuroprotective effect on CI/R injury by activating the PINK1-LETM1 signaling pathway, reducing the mitochondrial calcium overload, and promoting mitophagy.
4.Efficacy of direct-acting antiviral agents combined regimens for hepatitis C virus with different genotypes in Dehong Prefecture, Yunnan Province from 2022 to 2024
Renhai TANG ; Yidan ZHAO ; Yuecheng YANG ; Runhua YE ; Lifen XIANG ; Xingmei FENG ; Qunbo ZHOU ; Yanfen CAO ; Na HE ; Yingying DING ; Song DUAN
Shanghai Journal of Preventive Medicine 2025;37(8):676-681
ObjectiveTo investigate the therapeutic effects of direct-acting antiviral agents (DAAs) combined regimens for hepatitis C virus (HCV) patients in Dehong Prefecture, Yunnan Province from 2022 to 2024, to analyze the characteristics of treatment failure patients, so as to provide a basis for discovering more effective treatment regimens in the future. MethodsData on HCV prevention and treatment in Dehong Prefecture was extracted from the China Disease Control and Prevention Information System. A total of 617 patients with HCV antiviral therapy were included, and the differences in variable characteristics among patients with different genotypes were analyzed using comparative statistical tests, including basic socio-demographic characteristics, biochemical testing indicators, and information on previous treatment and current treatment. In addition, the cure rate of HCV patients with diverse characteristics was compared, and the potential causes of treatment failure were explored simultaneously. ResultsThe cure rate of HCV was 96.8%, and statistically significant differences were observed in aspartate transaminase (AST) and alanine transaminase (ALT) levels, previous antiviral therapy history and initial treatment regimens among patients with different HCV genotypes (all P<0.05). Among the multi-type combination regimens, the cure rate of sofosbuvir (SOF)-containing regimens was 97.00%, that of velpatasvir (VEL)-containing regimens was 95.45%, and the cure rate of other treatment regimens, including the regimens with ribavirin (RIB) intervention, was 93.10%. Among the patients with treatment failure, 45.00% had genotype 3, 40.00% had abnormal abdominal ultrasound results, and all presented with elevated baseline AST test levels. ConclusionThe clinical treatment of HCV patients should consider the differences in genotype and biochemical test results. DAAs combined regimens for HCV have achieved a high cure rate in Dehong Prefecture and are applicable to HCV patients with diverse clinical characteristics, providing research evidence for wider application.
5.Knowledge-embedded spatio-temporal analysis for euploidy embryos identification in couples with chromosomal rearrangements
Fangying CHEN ; Xiang XIE ; Du CAI ; Pengxiang YAN ; Chenhui DING ; Yangxing WEN ; Yanwen XU ; Feng GAO ; Canquan ZHOU ; Guanbin LI ; Qingyun MAI
Chinese Medical Journal 2024;137(6):694-703
Background::The goal of the assisted reproductive treatment is to transfer one euploid blastocyst and to help infertile women giving birth one healthy neonate. Some algorithms have been used to assess the ploidy status of embryos derived from couples with normal chromosome, who subjected to preimplantation genetic testing for aneuploidy (PGT-A) treatment. However, it is currently unknown whether artificial intelligence model can be used to assess the euploidy status of blastocyst derived from populations with chromosomal rearrangement.Methods::From February 2020 to May 2021, we collected the whole raw time-lapse videos at multiple focal planes from in vitro cultured embryos, the clinical information of couples, and the comprehensive chromosome screening results of those blastocysts that had received PGT treatment. Initially, we developed a novel deep learning model called the Attentive Multi-Focus Selection Network (AMSNet) to analyze time-lapse videos in real time and predict blastocyst formation. Building upon AMSNet, we integrated additional clinically predictive variables and created a second deep learning model, the Attentive Multi-Focus Video and Clinical Information Fusion Network (AMCFNet), to assess the euploidy status of embryos. The efficacy of the AMCFNet was further tested in embryos with parental chromosomal rearrangements. The receiver operating characteristic curve (ROC) was used to evaluate the superiority of the model. Results::A total of 4112 embryos with complete time-lapse videos were enrolled for the blastocyst formation prediction task, and 1422 qualified blastocysts received PGT-A ( n = 589) or PGT for chromosomal structural rearrangement (PGT-SR, n = 833) were enrolled for the euploidy assessment task in this study. The AMSNet model using seven focal raw time-lapse videos has the best real-time accuracy. The real-time accuracy for AMSNet to predict blastocyst formation reached above 70% on the day 2 of embryo culture, and then increased to 80% on the day 4 of embryo culture. Combing with 4 clinical features of couples, the AUC of AMCFNet with 7 focal points increased to 0.729 in blastocysts derived from couples with chromosomal rearrangement. Conclusion::Integrating seven focal raw time-lapse images of embryos and parental clinical information, AMCFNet model have the capability of assessing euploidy status in blastocysts derived from couples with chromosomal rearrangement.
6.Research progress on mechanism of interaction between traditional Chinese medicine and intestinal flora
Jing WU ; Wei-Yi TIAN ; Kun CAI ; Su-Fang ZHOU ; Yao-Feng LI ; Xiang-Yun CHEN ; Hai-Bing QIAN ; Sha-Sha YANG
Chinese Pharmacological Bulletin 2024;40(10):1823-1829
Modern Chinese medicine studies have confirmed that the interaction between traditional Chinese medicine(TCM)and intestinal flora is the key to the treatment of diseases with tradi-tional Chinese medicine.This interplay includes such activities as:traditional Chinese medicine can be metabolized by intestinal flora into effective components with different biological activities from its precursors;TCM chemicals improve the composition of gut microbiota,consequently ameliorating its dysfunction as well as associated pathological conditions;and gut microbiota mediate the interactions between the multiple chemicals in TCM.There-fore,it becomes an important way to understand the modern sci-entific connotation of traditional Chinese medicine theory to study the pharmacological mechanism of the efficacy of traditional Chi-nese medicine by targeting Gut microbiota.
7.The Association Between Causality Orientation and Internet Gaming Disorder, and the Role of Sensation Seeking, Anxiety, and Depression
Yanjie PENG ; Yuxiang WANG ; Zhenle PENG ; Xiaoyuan LIAO ; Ke GONG ; Cheng QIN ; Mingyuan TIAN ; Xiaotong CHENG ; Xinyi ZHOU ; Juan DENG ; Yuwen CHEN ; Shuang FENG ; Maomao ZHANG ; Kezhi LIU ; Bo XIANG ; Wei LEI ; Jing CHEN
Psychiatry Investigation 2024;21(11):1268-1278
Objective:
Self-determination theory (SDT) deems that people have three causality orientations: autonomy orientation, control orientation, and impersonal orientation. Previous studies suggested that lower autonomy orientation or higher control and impersonal orientations may be associated with more addictive behaviors. Our study aimed to investigate if these associations exist in Internet gaming disorder (IGD), and if sensation seeking, anxiety, and depression could influence the associations between causality orientations and IGD symptoms.
Methods:
A total of 1,400 college students completed the Internet Gaming Disorder Scale, General Causality Orientation Scale, Brief Sensation Seeking Scale, Generalized Anxiety Disorder Scale, and Patient Health Questionnaire. Correlation, multiple linear regressions, structural equation model (SEM) analyses, and moderation analyses were conducted to explore the associations.
Results:
The control and impersonal orientations were positively associated with IGD symptoms, while the autonomy orientation was negatively associated with them. Moreover, SEM analyses showed that the autonomy-IGD relationship was totally mediated by anxiety and depression, the impersonal-IGD relationship was partially mediated by anxiety, and the control-IGD relationship was partially mediated by depression. Finally, the effects of causality orientations on IGD were moderated by sensation seeking.
Conclusion
Overall, autonomy orientation is linked to fewer gaming problems, whereas control and impersonal orientations are associated with more gaming problems. Moreover, the relationships between causality orientations and IGD symptoms are mediated by anxiety and depression and moderated by sensation seeking. Our findings inform theory on the motivations of gaming behaviors and may shed light on the prevention and intervention of IGD from the perspective of SDT.
8.Application of O-RADS US combined with MV-Flow to diagnose ovarian-adnexal tumors
Linlin RUAN ; Hui LIU ; Hong XIANG ; Yongkang NI ; Yuling FENG ; Huili ZHOU ; Mengtong QI
Ultrasonography 2024;43(1):15-24
Purpose:
This study aimed to explore the application of Ovarian-Adnexal Reporting and Data System Ultrasound (O-RADS US) combined with MV-Flow (Samsung Medison Co., Ltd.) to diagnose ovarian-adnexal masses.
Methods:
A total of 112 ovarian-adnexal masses (81 benign and 31 malignant) from 105 consecutive patients were analyzed. The O-RADS US and vascular index from MV-Flow (VIMV) were measured and compared with the reference standard. O-RADS US and MV-Flow were tested for consistency.
Results:
Receiver operating characteristic curves were drawn for O-RADS US, MV-Flow, and their combination. The combined methods had the largest area under the curve (0.955), followed by O-RADS US (0.929) and MV-Flow (0.923). A mass was considered malignant when the O-RADS US classification was 5 and VIMV was ≥7.15. With this definition, MV-Flow had the highest sensitivity (87.10%), with consistent findings for the combined diagnostic methods and O-RADS US (83.87%). The specificity of the combined diagnostic methods (93.83%) was higher than that of MV-Flow (91.36%). O-RADS US had the lowest specificity (90.12%). The combined diagnostic methods had the highest coincidence rate (91.07%), and MV-Flow (90.18%) had a significantly higher coincidence rate than O-RADS US (88.39%). Both O-RADS US and MV-Flow showed good consistency among different physicians (former kappa, 0.974; latter intraclass correlation coefficient [ICC], 0.986). MV-Flow had a high consistency for the same physician (ICC, 1).
Conclusion
O-RADS US and MV-Flow exhibited good diagnostic efficacy, and their combined diagnostic efficacy was higher than that of each individually. O-RADS US and MV-Flow can improve the diagnosis of benign and malignant ovarian-adnexal masses.
9.Design of portable collection device for exhaled breath condensate
An XIANG ; Lei ZHOU ; Qi-Feng JI ; Yuan-Zhe LI ; Qin WANG ; Shi-Man ZHU ; Jie PENG ; Xiao-Ying LEI ; Wei-Na LI ; Li WANG ; Yan-Hai GUO ; Zi-Fan LU
Chinese Medical Equipment Journal 2024;45(8):32-37
Objective To develop a portable collection device of human exhaled breath condensate(EBC)based on natural breathing to meet the needs for rapid screening of human respiratory tract(especially lower respiratory tract)infections.Methods The device consisted of a refrigeration unit,a heat dissipation unit and a condensation unit.The refrigeration unit adopted a TES1-7102 thermoelectric Peltier cooler semiconductor as the refrigeration element;the heat dissipation unit was composed of a high thermal conductivity aluminum heat sink and a high-speed brushless cooling fan;the condensation unit was made up of a cold guide plate and a condenser,in which the cold guide plate was made of thin sheet of aluminum alloy,and the condenser was prepared by 3D printing technology and made of hydrophobic polylactic acid,with primary and secondary 2-stage guide grooves and an ultra-thin condensing surface.The performance of the device was verified in terms of cooling,thermal conductivity,condensation and human EBC collection and content analysis.Results Performance analysis showed that after refrigeration began the temperature difference between the condenser surface and the exhaled gas met the requirements of the condenser,and no obvious thermal resistance was found on the condensing surface so that large droplets could be formed rapidly and then be collected after the gas-liquid phase change of the exhaled gas on the condensing surface.Human EBC collection and content analysis indicated the device realized home self-collection of EBCs from people of all ages,and the concentrations of interleukins,C-reactive protein and other inflammation-related indexes and the pH value of the collected EBC samples were all correlated with respiratory infections in the subjects.Conclusion The device developed with easy operation avoids the discomfort of blowing collection and the risk of saliva contamination,and is worthy promoting for rapid diagnosis and dynamic monitoring of respiratory tract infection and other related diseases.[Chinese Medical Equipment Journal,2024,45(8):32-37]
10.The Association Between Causality Orientation and Internet Gaming Disorder, and the Role of Sensation Seeking, Anxiety, and Depression
Yanjie PENG ; Yuxiang WANG ; Zhenle PENG ; Xiaoyuan LIAO ; Ke GONG ; Cheng QIN ; Mingyuan TIAN ; Xiaotong CHENG ; Xinyi ZHOU ; Juan DENG ; Yuwen CHEN ; Shuang FENG ; Maomao ZHANG ; Kezhi LIU ; Bo XIANG ; Wei LEI ; Jing CHEN
Psychiatry Investigation 2024;21(11):1268-1278
Objective:
Self-determination theory (SDT) deems that people have three causality orientations: autonomy orientation, control orientation, and impersonal orientation. Previous studies suggested that lower autonomy orientation or higher control and impersonal orientations may be associated with more addictive behaviors. Our study aimed to investigate if these associations exist in Internet gaming disorder (IGD), and if sensation seeking, anxiety, and depression could influence the associations between causality orientations and IGD symptoms.
Methods:
A total of 1,400 college students completed the Internet Gaming Disorder Scale, General Causality Orientation Scale, Brief Sensation Seeking Scale, Generalized Anxiety Disorder Scale, and Patient Health Questionnaire. Correlation, multiple linear regressions, structural equation model (SEM) analyses, and moderation analyses were conducted to explore the associations.
Results:
The control and impersonal orientations were positively associated with IGD symptoms, while the autonomy orientation was negatively associated with them. Moreover, SEM analyses showed that the autonomy-IGD relationship was totally mediated by anxiety and depression, the impersonal-IGD relationship was partially mediated by anxiety, and the control-IGD relationship was partially mediated by depression. Finally, the effects of causality orientations on IGD were moderated by sensation seeking.
Conclusion
Overall, autonomy orientation is linked to fewer gaming problems, whereas control and impersonal orientations are associated with more gaming problems. Moreover, the relationships between causality orientations and IGD symptoms are mediated by anxiety and depression and moderated by sensation seeking. Our findings inform theory on the motivations of gaming behaviors and may shed light on the prevention and intervention of IGD from the perspective of SDT.

Result Analysis
Print
Save
E-mail