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.Expert Consensus on Clinical Application of Yifei Zhike Capsules
Xin CUI ; Hongchun ZHANG ; Weiwei GUO ; Chengjun BAN ; Zhifei WANG ; Yuanyuan LI ; Yingjie ZHI ; Xuefeng YU ; Yanming XIE
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(11):218-224
As an exclusive Miao medicine of Honwing Pharma (Guizhou) Co. Ltd., Yifei Zhike capsules are both a prescription drug and an over-the-counter (OTC) drug. Its main ingredients include Ranunculus ternatus and Panax notoginseng. With the effects of nourishing Yin and moistening the lungs, as well as relieving cough and reducing phlegm, Yifei Zhike capsules are often used in the treatment of acute and chronic bronchitis, pulmonary tuberculosis, and other diseases. However, there is insufficient understanding of their efficacy, suitable syndromes, and safety in clinical practice, with a lack of relevant expert consensus on clinical application. To standardize their clinical application, 30 experts from the fields of respiratory medicine, pharmacy, and evidence-based medicine were invited to develop an Expert Consensus on the Clinical Application of Yifei Zhike Capsules (Consensus for short) through evidence-based medicine methods. The Consensus clarified the syndrome characteristics, disease stages, dosages, treatment courses, combined medication, and other norms in the treatment of acute/chronic bronchitis and pulmonary tuberculosis and could be applicable to clinical physicians and pharmacists in medical and health institutions at all levels. In disease diagnosis, it provided diagnostic criteria for traditional Chinese medicine and Western medicine and clarified that the suitable traditional Chinese medicine syndrome was the syndrome of Qi-Yin deficiency with intermingled phlegm-blood stasis. Clinical studies have confirmed that Yifei Zhike capsules combined with standard anti-tuberculosis therapy can effectively improve the symptoms of pulmonary tuberculosis patients, increase the sputum smear conversion rate, and promote the absorption of lesions. When treating acute cough caused by respiratory tract infections, Yifei Zhike capsules can increase the markedly effective rate and the seven-day disappearance rate of cough symptoms. Meanwhile, recommendations for specific usage, dosages, and treatment courses were given for different diseases, and it was pointed out that long-term medication required key monitoring of adverse reactions. In safety, the adverse reactions of Yifei Zhike capsules involved multiple aspects such as the digestive system and allergic reactions, and pregnant women and women during menstruation were prohibited from using it. In addition, modern research has shown that Yifei Zhike capsules have an adjuvant therapeutic effect on tuberculous pleurisy and may be effective for inflammatory and benign pulmonary nodules. However, further research should be conducted on the toxicological safety of long-term medication. The formulation of the Consensus provides a scientific basis for the rational clinical application of Yifei Zhike capsules, which helps to improve clinical efficacy and reduce medication risks.
3.Expert Consensus on Clinical Application of Yifei Zhike Capsules
Xin CUI ; Hongchun ZHANG ; Weiwei GUO ; Chengjun BAN ; Zhifei WANG ; Yuanyuan LI ; Yingjie ZHI ; Xuefeng YU ; Yanming XIE
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(11):218-224
As an exclusive Miao medicine of Honwing Pharma (Guizhou) Co. Ltd., Yifei Zhike capsules are both a prescription drug and an over-the-counter (OTC) drug. Its main ingredients include Ranunculus ternatus and Panax notoginseng. With the effects of nourishing Yin and moistening the lungs, as well as relieving cough and reducing phlegm, Yifei Zhike capsules are often used in the treatment of acute and chronic bronchitis, pulmonary tuberculosis, and other diseases. However, there is insufficient understanding of their efficacy, suitable syndromes, and safety in clinical practice, with a lack of relevant expert consensus on clinical application. To standardize their clinical application, 30 experts from the fields of respiratory medicine, pharmacy, and evidence-based medicine were invited to develop an Expert Consensus on the Clinical Application of Yifei Zhike Capsules (Consensus for short) through evidence-based medicine methods. The Consensus clarified the syndrome characteristics, disease stages, dosages, treatment courses, combined medication, and other norms in the treatment of acute/chronic bronchitis and pulmonary tuberculosis and could be applicable to clinical physicians and pharmacists in medical and health institutions at all levels. In disease diagnosis, it provided diagnostic criteria for traditional Chinese medicine and Western medicine and clarified that the suitable traditional Chinese medicine syndrome was the syndrome of Qi-Yin deficiency with intermingled phlegm-blood stasis. Clinical studies have confirmed that Yifei Zhike capsules combined with standard anti-tuberculosis therapy can effectively improve the symptoms of pulmonary tuberculosis patients, increase the sputum smear conversion rate, and promote the absorption of lesions. When treating acute cough caused by respiratory tract infections, Yifei Zhike capsules can increase the markedly effective rate and the seven-day disappearance rate of cough symptoms. Meanwhile, recommendations for specific usage, dosages, and treatment courses were given for different diseases, and it was pointed out that long-term medication required key monitoring of adverse reactions. In safety, the adverse reactions of Yifei Zhike capsules involved multiple aspects such as the digestive system and allergic reactions, and pregnant women and women during menstruation were prohibited from using it. In addition, modern research has shown that Yifei Zhike capsules have an adjuvant therapeutic effect on tuberculous pleurisy and may be effective for inflammatory and benign pulmonary nodules. However, further research should be conducted on the toxicological safety of long-term medication. The formulation of the Consensus provides a scientific basis for the rational clinical application of Yifei Zhike capsules, which helps to improve clinical efficacy and reduce medication risks.
4.Compilation Instructions for Expert Consensus on Clinical Application of Yifei Zhike Capsules
Xin LI ; Hongchun ZHANG ; Xuefeng YU ; Weiwei GUO ; Chengjun BAN ; Zhifei WANG ; Yuanyuan LI ; Yingjie ZHI ; Xin CUI ; Yanming XIE
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(18):143-148
The compilation instructions for the Expert Consensus on Clinical Application of Yifei Zhike Capsules systematically expound the development background, methodological framework, and core achievements of this consensus. In view of the problems existing in the clinical application of Yifei Zhike Capsules, such as insufficient efficacy evidence and lack of standardized syndrome differentiation, the Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences took the lead and collaborated with 21 tertiary grade-A hospitals and research institutions across China to form a multidisciplinary expert group (comprising 30 experts in clinical medicine, pharmacy, and methodology). The compilation work was carried out in strict accordance with the World Health Organization (WHO) guidelines, the GB/T 1.1-2020 standard, and the writing specifications for the explanatory notes of expert consensus on clinical application of Chinese patent medicines. Through systematic literature retrieval (including 32 studies, with 24 clinical studies), Grading of Recommendations Assessment, Development and Evaluations (GRADE)-based evidence grading, and multiple rounds of discussions using the nominal group method (25 experts voted to determine 17 clinical questions), 5 evidence-based recommendations and 11 expert consensus suggestions were formed. It is clarified that this medicine (Yifei Zhike Capsules) is applicable to the treatment of expectoration/hemoptysis in acute and chronic bronchitis and the adjuvant treatment of pulmonary tuberculosis. It is recommended that it can be used alone or in combination with anti-tuberculosis drugs. The safety evaluation shows that this medicine mainly induces the following adverse reactions: mild gastrointestinal reactions (such as nausea and abdominal pain) and rashes. The contraindicated populations include pregnant women and women during menstruation. The compilation process of the consensus underwent three rounds of expert letter reviews, two rounds of peer reviews, and quality control assessments to ensure methodological rigor and clinical applicability. In addition, through policy alignment, academic promotion, and a dynamic revision mechanism, the standardization of clinical application was promoted, providing a demonstration for the evidence-based transformation of characteristic therapies of Miao medicine.
5.Rapid Screening of 34 Emerging Contaminants in Surface Water by UHPLC-Q-TOF-MS
Chen-Shan LÜ ; Yi-Xuan CAO ; Xiao-Xi MU ; Hai-Yan CUI ; Tao WANG ; Zhi-Wen WEI ; Ke-Ming YUN ; Meng HU
Journal of Forensic Medicine 2024;40(1):30-36
Objective To establish a rapid screening method for 34 emerging contaminants in surface water by ultra-high performance liquid chromatography-quadrupole-time of flight mass spectrometry(UHPLC-Q-TOF-MS).Methods The pretreatment conditions of solid phase extraction(SPE)were op-timized by orthogonal experimental design and the surface water samples were concentrated and ex-tracted by Oasis? HLB and Oasis? MCX SPE columns in series.The extracts were separated by Kine-tex? EVO C18 column,with gradient elution of 0.1%formic acid aqueous solution and 0.1%formic acid methanol solution.Q-TOF-MS'fullscan'and'targeted MS/MS'modes were used to detect 34 emerging contaminants and to establish a database with 34 emerging contaminants precursor ion,prod-uct ion and retention times.Results The 34 emerging contaminants exhibited good linearity in the con-centration range respectively and the correlation coefficients(r)were higher than 0.97.The limit of de-tection was 0.2-10 ng/L and the recoveries were 81.2%-119.2%.The intra-day precision was 0.78%-18.70%.The method was applied to analyze multiple surface water samples and 6 emerging contaminants were detected,with a concentration range of 1.93-157.71 ng/L.Conclusion The method is simple and rapid for screening various emerging contaminants at the trace level in surface water.
6.Construction of the quality evaluation scale of specification of management for humanistic caring in outpatients and its reliability and validity testing
Lixia YUE ; Na CUI ; Xu CHE ; Heng ZHANG ; Hongxia WANG ; Shujie GUO ; Hongling SHI ; Ruiying YU ; Xia XIN ; Xiaohuan CHEN ; Li WANG ; Zhiwei ZHI ; Lei TAN ; Xican ZHENG
Chinese Medical Ethics 2024;37(11):1366-1377
Objective:To construct the quality evaluation scale of specification of management for humanistic caring in outpatients and test its reliability and validity.Methods:Referring to the group standards in Specification of Management for Humanistic Caring in Outpatients released by the China Association for Life Care,as well as relevant guidelines and literature,a pool of items for the quality evaluation scale of specification of management for humanistic caring in outpatients was formed.After expert consultation and expert argumentation,a quality evaluation scale of specification of management for humanistic caring in outpatients was constructed.From January to February 2024,243 hospital managers from 5 hospitals in Zhengzhou were selected as survey subjects to conduct item analysis,and reliability and validity testing on the scale.Results:Two rounds of expert inquiry and two rounds of expert argumentation were conducted,with questionnaire response rates of 92.00%and 100.00%,respectively,and expert authority coefficients of 0.952.In the second round of the expert inquiry scale,the mean importance score of the first-level indicators was 4.80 to 5.00,the full score ratio was 88.00%to 100.00%,the coefficient of variation was 0.04 to 0.17,and Kendall's coefficient of concordance was 0.857(P<0.001);the mean importance score of the second-level indicators was 4.60 to 5.00,the full score ratio was 80.00%to 100.00%,the coefficient of variation was 0.00 to 0.21,and Kendall's coefficient of concordance was 0.775(P<0.001);the mean importance score of the third-level indicators was 4.60 to 5.00,the full score ratio was 76.00%to 100.00%,the coefficient of variation was 0.00 to 0.21,and Kendall's coefficient of concordance was 0.830(P<0.001).Finally,a quality evaluation scale of specification of management for humanistic caring in outpatients was formed,including 5 first-level indicators,25 second-level indicators,and 58 third-level indicators.Exploratory factor analysis produced 5 common factors with a cumulative variance contribution rate of 74.628%.The Pearson correlation coefficients between the five-factor scores ranged from 0.648 to 0.798,and the correlation coefficients between the factor scores and the total score of the scale ranged from 0.784 to 0.938.The scale-level content validity index(S-CVI)of the scale was 0.945,the item-content validity index(I-CVI)was 0.725 to 1.000,the Cronbach's alpha coefficient of the total scale was 0.973,and the retest reliability coefficient was 0.934.Conclusion:The constructed quality evaluation scale of specification of management for humanistic caring in outpatients has good scientific validity and reliability,and can be used as an evaluation tool for specification of management for humanistic caring in outpatients.
7.Global trends in the incidence and prevalence of pneumoconiosis in 204 countries/territories from 1990 to 2019
Shihao TANG ; Jiaxin CUI ; Yuquan CHEN ; Qiuyuan MAI ; Jinwei ZHANG ; Zhi WANG
Chinese Journal of Industrial Hygiene and Occupational Diseases 2024;42(2):123-128
Objective:To analyze the changing trend of incidence and prevalence of pneumoconiosis globally, and provide scientific basis for the formulation of health policy.Methods:In June 2022, through the Global Health Data exchange (GHDx) query tool (http: //ghdx.healthdata.org/gbd-results-tool) , the pneumoconiosis incidence and prevalence data was downloaded and organized. Estimated annual percentage change (EAPC) and age-standardized rate (ASR) were used to estimate the trends of pneumoconiosis from 1990 to 2019. EAPC was estimated by linear regression model based on ASR.Results:The overall ASR of the incidence and prevalence of pneumoconiosis decreased from 1990 to 2019, and their EAPCs were-0.85% (95% CI: -1.11%--0.60%) and -0.78% (95% CI: -1.08%--0.49%) . Over the past 30 years, the incidence and prevalence of pneumoconiosis in all SDI areas showed decreasing trends, especially in high SDI areas, their EAPCs were -1.46% (95% CI: -1.76%--1.15%) and -1.99% (95% CI: -2.44%--1.53%) . 110 countries/areas showed increasing trends in age standardized incidence rate (ASIR) , with Iran and Georgia showing the most pronounced upward trend, their EAPCs were 5.32% (95% CI: 4.43%-6.22%) and 4.39% (95% CI: 3.81%-4.97%) . 125 countries/areas showed anincreasing trends in prevalence ASR, with Iran had the fastest rise in prevalence (EAPC=6.40%, 95% CI: 5.33%-7.49%) . Conclusion:Although decreasing trends in the burden of pneumoconiosis are observed globally from 1990 to 2019, but the burden of pneumoconiosis in low-and middle-income countries or regions are still heavy. We need more effective strategies to prevent and reduce the burden of pneumoconiosis.
8.Cardiac MR tissue tracking technique for quantitatively evaluating myocardial strain of cardiac amyloidosis patients
Jiangkai HE ; Chen CUI ; Wei MA ; Zhi WANG ; Jia LIU ; Wei LI ; Kai ZHAO ; Rile NAI ; Shasha XU ; Jianxing QIU
Chinese Journal of Interventional Imaging and Therapy 2024;21(1):42-47
Objective To observe the feasibility of cardiac MR tissue tracking(CMR-TT)technique for quantitatively evaluating myocardial strain of patients with myocardial amyloidosis(CA).Methods Cardiac MRI were collected from 20 patients of immunoglobulin amyloid light-chain CA(AL-CA,group A),20 cases of transthyretin CA(ATTR-CA,group B)and 20 healthy subjects(group C),and myocardial strain parameters were obtained using CMR-TT technique.Left ventricular cardiac function parameters were compared among 3 groups,so were strain parameters of each myocardial segment of left ventricle and global myocardium,including 3D longitudinal strain(LS),3D radial strain(RS)and 3D circumferential strain(CS).Results Compared with those in group C,significant differences of left ventricular cardiac function parameters were found in both group A and B(all P<0.01),while no statistical difference was found between group A and B(all P>0.05).Except for apical segment RS(P=0.81),strain parameters in group A and B were both lower than those in group C(all P<0.01),while no significant difference was detected between group A and B(all P>0.05).Conclusion CMR-TT technique could be used to quantitatively evaluate left ventricular myocardial strain of CA patients.
9.A recombinant adeno-associated virus expressing secretory TGF-β type Ⅱ receptor inhibits triple-negative murine breast cancer 4T1 cell proliferation and lung metastasis in mice
Zhi CUI ; Cuijiao MA ; Qianru WANG ; Jinhao CHEN ; Ziyang YAN ; Jianlin YANG ; Yafeng LÜ ; Chunyu CAO
Journal of Southern Medical University 2024;44(5):818-826
Objective To investigate the effects of an adeno-associated virus(AAV2)vector expressing secretory transforming growth factor-β(TGF-β)type Ⅱ receptor(sTβRⅡ)extracellular domain-IgG2a Fc fusion protein(sTβRⅡ-Fc)on proliferation and migration of triple-negative murine breast cancer 4T1 cells in mice.Methods The pAAV-sTβRⅡ-Fc vector expressing sTβRⅡ-Fc fusion protein constructed by molecular cloning,the capsid protein-expressing vector pAAV2 and the helper vector were co-transfected into HEK 293T cells to prepare the recombinant AAV2-sTβRⅡ virus,which was purified by density gradient centrifugation with iodixanol.Western blotting was used to examine the effects of AAV-sTβRⅡ virus on Smad2/3 phosphorylation in 4T1 cells and on expression levels of E-cadherin,vimentin and p-Smad2/3 in 4T1 cell xenografts in mice.BALB/c mice bearing subcutaneous xenografts of luciferase-expressing 4T1 cells received intravenous injections of AAV-sTβRⅡ virus,AAV-GFP virus or PBS(n=6)through the tail vein,and the proliferation and migration of 4T1 cells were analyzed with in vivo imaging.Ki67 expression in the tumor tissues and sTβRⅡ protein expressions in mouse livers were detected with immunohistochemistry and immunofluorescence staining,and tumor metastases in the vital organs were examined with HE staining.Results The recombinant pAAV-sTβRⅡ-Fc vector successfully expressed sTβRⅡ in HEK 293T cells.Infection with AAV2-sTβRⅡ virus significantly reduced TGF-β1-induced Smad2/3 phosphorylation in 4T1 cells and effectively inhibited proliferation and lung metastasis of 4T1 xenografts in mice(P<0.05).In the tumor-bearing mice,intravenous injection of AAV-sTβRⅡ virus significantly increased E-cadherin expression,reduced vimentin and Ki67 protein expressions and Smad2/3 phosphorylation level in the tumor tissues(P<0.05 or 0.01),and induced liver-specific sTβRⅡ expression without causing body weight loss or heart,liver,spleen or kidney pathologies.Conclusion The recombinant AVV2 vector encoding sTβRⅡ extracellular domain is capable of blocking the TGF-β signaling pathway to inhibit the proliferation and lung metastasis of 4T1 cells in mice.
10.2-(2-Phenylethyl)chromones from agarwood of Aquilaria agallocha and their inhibitory activity against KRAS mutant NSCLC
Bao-juan XING ; Yi-fan FU ; He CUI ; Qian ZHOU ; Zhi-kang WANG ; Peng CAO ; Fa-ping BAI ; Xue-ting CAI
Acta Pharmaceutica Sinica 2024;59(9):2519-2528
The 2-(2-phenylethyl)chromones were separated from agarwood of

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