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.Advances in application of small-molecule compounds in neuronal reprogramming.
Zi-Wei DAI ; Hong LIU ; Yi-Min YUAN ; Jing-Yi ZHANG ; Shang-Yao QIN ; Zhi-Da SU
Acta Physiologica Sinica 2025;77(1):181-193
Neuronal reprogramming is an innovative technique for converting non-neuronal somatic cells into neurons that can be used to replace lost or damaged neurons, providing a potential effective therapeutic strategy for central nervous system (CNS) injuries or diseases. Transcription factors have been used to induce neuronal reprogramming, while their reprogramming efficiency is relatively low, and the introduction of exogenous genes may result in host gene instability or induce gene mutation. Therefore, their future clinical application may be hindered by these safety concerns. Compared with transcription factors, small-molecule compounds have unique advantages in the field of neuronal reprogramming, which can overcome many limitations of traditional transcription factor-induced neuronal reprogramming. Here, we review the recent progress in the research of small-molecule compound-mediated neuronal reprogramming and its application in CNS regeneration and repair.
Humans
;
Cellular Reprogramming/drug effects*
;
Neurons/cytology*
;
Animals
;
Transcription Factors
;
Small Molecule Libraries/pharmacology*
;
Nerve Regeneration
3.Three-dimensional Heterogeneity and Intrinsic Plasticity of the Projection from the Cerebellar Interposed Nucleus to the Ventral Tegmental Area.
Chen WANG ; Si-Yu WANG ; Kuang-Yi MA ; Zhao-Xiang WANG ; Fang-Xiao XU ; Zhi-Ying WU ; Yan GU ; Wei CHEN ; Ying SHEN ; Li-Da SU ; Lin ZHOU
Neuroscience Bulletin 2025;41(1):159-164
4.Clinical practice guidelines for the diagnosis and treatment of atopic dermatitis with integrative traditional Chinese and Western medicine.
Xin-Ran DU ; Meng-Yi WU ; Mao-Can TAO ; Ying LIN ; Chao-Ying GU ; Min-Feng WU ; Yi CAO ; Da-Can CHEN ; Wei LI ; Hong-Wei WANG ; Ying WANG ; Yi WANG ; Han-Zhi LU ; Xin LIU ; Xiang-Fei SU ; Fu-Lun LI
Journal of Integrative Medicine 2025;23(6):641-653
Traditional Chinese medicine (TCM) is a well-accepted therapy for atopic dermatitis (AD). However, there are currently no evidence-based guidelines integrating TCM and Western medicine for the treatment of AD, limiting the clinical application of such combined approaches. Therefore, the China Association of Chinese Medicine initiated the development of the current guideline, focusing on key issues related to the use of TCM in the treatment of AD. This guideline was developed in accordance with the principles of the guideline formulation manual published by the World Health Organization. A comprehensive review of the literature on the combined use of TCM and Western medicine to treat AD was conducted. The findings were extensively discussed by experts in dermatology and pharmacy with expertise in both TCM and Western medicine. This guideline comprises 23 recommendations across seven major areas, including TCM syndrome differentiation and classification of AD, principles and application scenarios of TCM combined with Western medicine for treating AD, outcome indicators for evaluating clinical efficacy of AD treatment, integration of TCM pattern classification and Western medicine across disease stages, daily management of AD, the use of internal TCM therapies and proprietary Chinese medicines, and TCM external treatments. Please cite this article as: Du XR, Wu MY, Tao MC, Lin Y, Gu CY, Wu MF, Cao Y, Chen DC, Li W, Wang HW, Wang Y, Wang Y, Lu HZ, Liu X, Su XF, Li FL. Clinical practice guidelines for the diagnosis and treatment of atopic dermatitis with integrative traditional Chinese and Western medicine. J Integr Med. 2025; 23(6):641-653.
Dermatitis, Atopic/drug therapy*
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Humans
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Medicine, Chinese Traditional/methods*
;
Integrative Medicine
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Drugs, Chinese Herbal/therapeutic use*
;
Practice Guidelines as Topic
5.Development and global validation of a 1-week-old piglet head finite element model for impact simulations.
Zhong-Qing SU ; Da-Peng LI ; Rui LI ; Guang-Liang WANG ; Lang LIU ; Ya-Feng WANG ; Ya-Zhou GUO ; Zhi-Gang LI
Chinese Journal of Traumatology 2023;26(3):147-154
PURPOSE:
Child head injury under impact scenarios (e.g. falls, vehicle crashes, etc.) is an important topic in the field of injury biomechanics. The head of piglet was commonly used as the surrogate to investigate the biomechanical response and mechanisms of pediatric head injuries because of the similar cellular structures and material properties. However, up to date, piglet head models with accurate geometry and material properties, which have been validated by impact experiments, are seldom. We aim to develop such a model for future research.
METHODS:
In this study, first, the detailed anatomical structures of the piglet head, including the skull, suture, brain, pia mater, dura mater, cerebrospinal fluid, scalp and soft tissue, were constructed based on CT scans. Then, a structured butterfly method was adopted to mesh the complex geometries of the piglet head to generate high-quality elements and each component was assigned corresponding constitutive material models. Finally, the guided drop tower tests were conducted and the force-time histories were ectracted to validate the piglet head finite element model.
RESULTS:
Simulations were conducted on the developed finite element model under impact conditions and the simulation results were compared with the experimental data from the guided drop tower tests and the published literature. The average peak force and duration of the guide drop tower test were similar to that of the simulation, with an error below 10%. The inaccuracy was below 20%. The average peak force and duration reported in the literature were comparable to those of the simulation, with the exception of the duration for an impact energy of 11 J. The results showed that the model was capable to capture the response of the pig head.
CONCLUSION
This study can provide an effective tool for investigating child head injury mechanisms and protection strategies under impact loading conditions.
Animals
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Swine
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Finite Element Analysis
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Skull/injuries*
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Craniocerebral Trauma/diagnostic imaging*
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Brain
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Biomechanical Phenomena
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Scalp
6.Analysis of clinical phenotype and genotype of Chinese children with disorders of sex development.
Hu LIN ; Hao YANG ; Jun Fen FU ; Jin Na YUAN ; Ke HUANG ; Wei WU ; Guan Ping DONG ; Hong Juan TIAN ; De Hua WU ; Da Xing TANG ; Ding Wen WU ; Li Ying SUN ; Ya Lei PI ; Li Jun LIU ; Li Ping SHI ; Wei GU ; Lu Gang HUANG ; Yi Hua WANG ; Lin Qi CHEN ; Hong Ying LI ; Yang YU ; Hai Yan WEI ; Xin Ran CHENG ; Xiao Ou SHAN ; Yu LIU ; Xu XU ; Shu LIU ; Xiao Ping LUO ; Yan Feng XIAO ; Yu YANG ; Gui Mei LI ; Mei FENG ; Xiu Qi MA ; Dao Xiang PAN ; Jia Yan TANG ; Rui Min CHEN ; Mireguli MAIMAITI ; De Yun LIU ; Xin Hai CUI ; Zhe SU ; Zhi Qiao DONG ; Li ZOU ; Yan Ling LIU ; Jin WU ; Kun Xia LI ; Yuan LI
Chinese Journal of Pediatrics 2022;60(5):435-441
Objective: To explore the heterogeneity and correlation of clinical phenotypes and genotypes in children with disorders of sex development (DSD). Methods: A retrospective study of 1 235 patients with clinically proposed DSD in 36 pediatric medical institutions across the country from January 2017 to May 2021. After capturing 277 DSD-related candidate genes, second-generation sequencing was performed to analyzed the heterogeneity and correlation combined with clinical phenotypes. Results: Among 1 235 children with clinically proposed DSD, 980 were males and 255 were females of social gender at the time of initial diagnosis with the age ranged from 1 day of age to 17.92 years. A total of 443 children with pathogenic variants were detected through molecular genetic studies, with a positive detection rate of 35.9%. The most common clinical phenotypes were micropenis (455 cases), hypospadias (321 cases), and cryptorchidism (172 cases) and common mutations detected were in SRD5A2 gene (80 cases), AR gene (53 cases) and CYP21A2 gene (44 cases). Among them, the SRD5A2 mutation is the most common in children with simple micropenis and simple hypospadias, while the AMH mutation is the most common in children with simple cryptorchidism. Conclusions: The SRD5A2 mutation is the most common genetic variant in Chinese children with DSD, and micropenis, cryptorchidism, and hypospadias are the most common clinical phenotypes. Molecular diagnosis can provide clues about the biological basis of DSD, and can also guide clinicians to perform specific clinical examinations. Target sequence capture probes and next-generation sequencing technology can provide effective and economical genetic diagnosis for children with DSD.
3-Oxo-5-alpha-Steroid 4-Dehydrogenase/genetics*
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Child
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China/epidemiology*
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Cryptorchidism/genetics*
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Disorders of Sex Development/genetics*
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Female
;
Genital Diseases, Male
;
Genotype
;
Humans
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Hypospadias/genetics*
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Male
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Membrane Proteins/genetics*
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Penis/abnormalities*
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Phenotype
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Retrospective Studies
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Steroid 21-Hydroxylase/genetics*
7.Biological characteristics and functions of NG2-glia.
Hong LIU ; Yi-Min YUAN ; Shang-Yao QIN ; Tao LIU ; Zhi-Da SU
Acta Physiologica Sinica 2021;73(6):940-952
NG2-glia are a major type of glial cells that are widely distributed in the central nervous system (CNS). Under physiological conditions, they mainly differentiate into oligodendrocytes and contribute to the myelination of axons, so they are generally called oligodendrocyte progenitor cells. Emerging evidence suggests that NG2-glia not only act as the precursors of oligodendrocytes but also possess many other biological properties and functions. For example, NG2-glia can form synapse with neurons and participate in energy metabolism and immune regulation. Under pathological conditions, NG2-glia can also differentiate into astrocytes, Schwann cells and even neurons, which are involved in CNS injury and repair. Therefore, a deeper understanding of the biological characteristics and functions of NG2-glia under physiological and pathological conditions will be helpful for the treatment of CNS injury and disease. This article reviews the recent advances in the biological characteristics and functions of NG2-glia.
Astrocytes
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Central Nervous System
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Neuroglia
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Neurons
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Oligodendroglia
8.Anti-cyclic citrullinated peptide antibody predicts the development of rheumatoid arthritis in patients with undifferentiated arthritis
Li CHUN ; Zhang YAN ; Song HUI ; Gao JIE ; Zhao DONG-BAO ; Zhu QI ; He DONG-YI ; Wang LI ; Li XIANG-PEI ; Liu XU-DONG ; Xiao WEI-GUO ; Wu XIN-YU ; Wu HUA-XIANG ; Tu WEI ; Hu SHAO-XIAN ; Wang XIN ; Li ZHI-JUN ; Lu ZHI-MIN ; Da ZHAN-YUN ; Liang BO ; Liu XIAO-MIN ; Zhao JIN-WEI ; Li LING ; Han FENG ; Qi WU-FANG ; Wei WEI ; Ma XU ; Li ZHEN-BIN ; Zheng GUI-MIN ; Zhang FENG-XIAO ; Li YI ; Wang YOU-LIAN ; Ling GUANG-HUI ; Chen JIN-WEI ; Hou XIAO-QIANG ; Zhang JING ; Chen QING-PING ; Liu CHANG-LIAN ; Zhang YAN ; Zeng JIA-SHUN ; Zou QING-HUA ; Fang YONG-FEI ; Su YIN ; Li ZHAN-GUO
Chinese Medical Journal 2019;132(24):2899-2904
Background:Clinical outcomes of undifferentiated arthritis (UA) are diverse,and only 40 % of patients with UA develop rheumatoid arthritis (RA) after 3 years.Discovering predictive markers at disease onset for further intervention is critical.Therefore,our objective was to analyze the clinical outcomes of UA and ascertain the predictors for RA development.Methods:We performed a prospective,multi-center study from January 2013 to October 2016 among Chinese patients diagnosed with UA in 22 tertiary-care hospitals.Clinical and serological parameters were obtained at recruitment.Follow-up was undertaken in all patients every 12 weeks for 2 years.Predictive factors of disease progression were identified using multivariate Cox proportional hazards regression.Results:A total of 234 patients were recruited in this study,and 17 (7.3%) patients failed to follow up during the study.Among the 217 patients who completed the study,83 (38.2%) patients went into remission.UA patients who developed RA had a higher rheumatoid factor (RF)-positivity (42.9% vs.16.8%,x2=8.228,P=0.008),anti-cyclic citrullinated peptide (CCP) antibodypositivity (66.7% vs.10.7%,x2 =43.897,P < 0.001),and double-positivity rate of RF and anti-CCP antibody (38.1% vs.4.1%,x2 =32.131,P < 0.001) than those who did not.Anti-CCP antibody but not RF was an independent predictor for RA development (hazard ratio 18.017,95% confidence interval:5.803-55.938;P < 0.001).Conclusion:As an independent predictor of RA,anti-CCP antibody should be tested at disease onset in all patients with UA.
9.Expert consensus statement on Diemailing~® Kudiezi Injection in clinical practice.
Xing LIAO ; Yun-Ling ZHANG ; Yan-Ming XIE ; Da-Zhuo SHI ; Su-Lun SUN ; Yi-Huai ZOU ; Jun LI ; Wei-Xing LU ; Mei JIN ; Hong-Xu LIU ; Xue-Chun TANG ; Xiang-Lan JIN ; Yun-Zhi MA ; Si-Yan ZHAN ; Jian-Ping LIU ; Yao-Long CHEN
China Journal of Chinese Materia Medica 2019;44(14):2926-2931
Diemailing~® Kudiezi Injection( DKI) is widely used in the treatment of cerebral infarction,coronary heart disease and angina pectoris. Long-term clinical application and related research evidence showed that DKI has a good effect in improving the clinical symptoms of cardiovascular and cerebrovascular diseases. However,this injection has not been included in any clinical practice guideline. It has been found that the use of DKI is in wrong way in clinical practice in recent years. Therefore,clinical experts from the field of cardiovascular and cerebrovascular diseases nationwide are invited to compile this expert consensus in order to guide clinicians.GRADE system is used to grade the quality of evidence according to different outcomes according to degrading factors. Then it forms the recommendation or consensus suggestion through the nominal group method. The formation of expert consensus mainly considers six factors: quality of evidence,economy,efficacy,adverse reactions,patient acceptability and others. Based on these six aspects,if the evidence is sufficient,a " recommendation" supported by evidence is formed,and GRADE grid voting rule is adopted. If the evidence is insufficient,a " consensus suggestions" will be formed,using the majority voting rule. In this consensus,the clinical indications,efficacy,safety evidences and related preliminary data of DKI were systematically and comprehensively summarized in a concise and clear format,which could provide valuable reference for the clinical use of DKI. This consensus has been approved by China association of Chinese medicine which is numbered GS/CACM 202-2019.
Angina Pectoris
;
drug therapy
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Cerebral Infarction
;
drug therapy
;
China
;
Consensus
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Coronary Disease
;
drug therapy
;
Drugs, Chinese Herbal
;
therapeutic use
;
Humans
;
Injections
;
Medicine, Chinese Traditional
10.Intranasal Immunization Using CTA1-DD as a Mucosal Adjuvant for an Inactivated Influenza Vaccine.
Xue Ting FAN ; Yun Long WANG ; Qiu Dong SU ; Feng QIU ; Yao YI ; Zhi Yuan JIA ; Da Yan WANG ; Kun QIN ; Ye Ning ZOU ; Sheng Li BI ; Li Ping SHEN
Biomedical and Environmental Sciences 2019;32(7):531-540
OBJECTIVE:
To evaluate the effect of intranasal immunization with CTA1-DD as mucosal adjuvant combined with H3N2 split vaccine.
METHODS:
Mice were immunized intranasally with PBS (negative control), or H3N2 split vaccine (3 μg/mouse) alone, or CTA1-DD (5 μg/mouse) alone, or H3N2 split vaccine (3 μg/mouse) plus CTA1-DD (5 μg/mouse). Positive control mice were immunized intramuscularly with H3N2 split vaccine (3 μg/mouse) and alum adjuvant. All the mice were immunized twice, two weeks apart. Then sera and mucosal lavages were collected. The specific HI titers, IgM, IgG, IgA, and IgG subtypes were examined by ELISA. IFN-γ and IL-4 were test by ELISpot. In addition, two weeks after the last immunization, surivival after H3N2 virus lethal challenge was measured.
RESULTS:
H3N2 split vaccine formulated with CTA1-DD could elicit higher IgM, IgG and hemagglutination inhibition titers in sera. Furthermore, using CTA1-DD as adjuvant significantly improved mucosal secretory IgA titers in bronchoalveolar lavages and vaginal lavages. Meanwhile this mucosal adjuvant could enhance Th-1-type responses and induce protective hemagglutination inhibition titers. Notably, the addition of CTA1-DD to split vaccine provided 100% protection against lethal infection by the H3N2 virus.
CONCLUSION
CTA1-DD could promote mucosal, humoral and cell-mediated immune responses, which supports the further development of CTA1-DD as a mucosal adjuvant for mucosal vaccines.
Adjuvants, Immunologic
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Administration, Intranasal
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Animals
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Cholera Toxin
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Female
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Immunity, Humoral
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Influenza A Virus, H3N2 Subtype
;
immunology
;
Influenza Vaccines
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Mice, Inbred BALB C
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Nasal Mucosa
;
immunology
;
Random Allocation
;
Recombinant Fusion Proteins

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