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.Protective effect of sub-hypothermic mechanical perfusion combined with membrane lung oxygenation on a yorkshire model of brain injury after traumatic blood loss.
Xiang-Yu SONG ; Yang-Hui DONG ; Zhi-Bo JIA ; Lei-Jia CHEN ; Meng-Yi CUI ; Yan-Jun GUAN ; Bo-Yao YANG ; Si-Ce WANG ; Sheng-Feng CHEN ; Peng-Kai LI ; Heng CHEN ; Hao-Chen ZUO ; Zhan-Cheng YANG ; Wen-Jing XU ; Ya-Qun ZHAO ; Jiang PENG
Chinese Journal of Traumatology 2025;28(6):469-476
PURPOSE:
To investigate the protective effect of sub-hypothermic mechanical perfusion combined with membrane lung oxygenation on ischemic hypoxic injury of yorkshire brain tissue caused by traumatic blood loss.
METHODS:
This article performed a random controlled trial. Brain tissue of 7 yorkshire was selected and divided into the sub-low temperature anterograde machine perfusion group (n = 4) and the blank control group (n = 3) using the random number table method. A yorkshire model of brain tissue injury induced by traumatic blood loss was established. Firstly, the perfusion temperature and blood oxygen saturation were monitored in real-time during the perfusion process. The number of red blood cells, hemoglobin content, NA+, K+, and Ca2+ ions concentrations and pH of the perfusate were detected. Following perfusion, we specifically examined the parietal lobe to assess its water content. The prefrontal cortex and hippocampus were then dissected for histological evaluation, allowing us to investigate potential regional differences in tissue injury. The blank control group was sampled directly before perfusion. All statistical analyses and graphs were performed using GraphPad Prism 8.0 Student t-test. All tests were two-sided, and p value of less than 0.05 was considered to indicate statistical significance.
RESULTS:
The contents of red blood cells and hemoglobin during perfusion were maintained at normal levels but more red blood cells were destroyed 3 h after the perfusion. The blood oxygen saturation of the perfusion group was maintained at 95% - 98%. NA+ and K+ concentrations were normal most of the time during perfusion but increased significantly at about 4 h. The Ca2+ concentration remained within the normal range at each period. Glucose levels were slightly higher than the baseline level. The pH of the perfusion solution was slightly lower at the beginning of perfusion, and then gradually increased to the normal level. The water content of brain tissue in the sub-low and docile perfusion group was 78.95% ± 0.39%, which was significantly higher than that in the control group (75.27% ± 0.55%, t = 10.49, p < 0.001), and the difference was statistically significant. Compared with the blank control group, the structure and morphology of pyramidal neurons in the prefrontal cortex and CA1 region of the hippocampal gyrus were similar, and their integrity was better. The structural integrity of granulosa neurons was destroyed and cell edema increased in the perfusion group compared with the blank control group. Immunofluorescence staining for glail fibrillary acidic protein and Iba1, markers of glial cells, revealed well-preserved cell structures in the perfusion group. While there were indications of abnormal cellular activity, the analysis showed no significant difference in axon thickness or integrity compared to the 1-h blank control group.
CONCLUSIONS
Mild hypothermic machine perfusion can improve ischemia and hypoxia injury of yorkshire brain tissue caused by traumatic blood loss and delay the necrosis and apoptosis of yorkshire brain tissue by continuous oxygen supply, maintaining ion homeostasis and reducing tissue metabolism level.
Animals
;
Perfusion/methods*
;
Disease Models, Animal
;
Brain Injuries/etiology*
;
Swine
;
Male
;
Hypothermia, Induced/methods*
3.Diverse Subtypes of Cardiovascular Disease Risk Evaluated by Novel PREVENT Associated with Different Polycyclic Aromatic Hydrocarbon Metabolites.
Ye XIN ; Yu Cheng SUN ; Lin CHEN ; Feng Tao CUI ; Ying Ge DUAN ; Han Yun WANG ; Li CHEN ; Tian CHEN ; Pi Ye NIU ; Jun Xiang MA
Biomedical and Environmental Sciences 2025;38(10):1217-1229
OBJECTIVE:
To investigate the association of various polycyclic aromatic hydrocarbon (PAH) metabolites with diverse subtypes of cardiovascular disease (CVD) risk.
METHODS:
A novel predicting risk of cardiovascular disease EVENTs PREVENT equation was used to estimate the 10-year diverse subtypes of CVD risk, and their associations with PAH metabolites were analyzed using multiple logistic regression models, the weighted quantile sum (WQS) model, the quantile g-computation (qgcomp) model, and a stratified analysis of subgroups.
RESULTS:
For this study, six thousand seven hundred and forty-five participants were selected, and significant positive associations were observed between PAHs, naphthalene (NAP), and fluorene (FLU), and the risks of total CVD, atherosclerotic cardiovascular disease (ASCVD), and heart failure (HF). NAP and FLU were the primary contributors to the effects of PAH mixtures, and their associations with total CVD, ASCVD, and HF risk were significant in younger participants (30 ≤ age < 50 years); however, the associations of phenanthrene (PHEN) with ASCVD, HF, coronary heart disease (CHD), and stroke were dominant in aging participants (age ≥ 50 years). Notably, pyrene (PYR) was negatively associated with the risk of ASCVD, HF, CHD, and stroke. Similarly, negative associations of PYR with the four CVD subtypes were noticeable in aging participants.
CONCLUSION
Different PAHs metabolites had different impacts on each CVD subtype among different age groups. Notably, the protective effects of PYR on ASCVD, HF, CHD, and stroke were noticeable in aging individuals.
Humans
;
Cardiovascular Diseases/chemically induced*
;
Middle Aged
;
Polycyclic Aromatic Hydrocarbons/metabolism*
;
Male
;
Female
;
Adult
;
Aged
;
Risk Factors
;
China/epidemiology*
4.Factors and Their Impact on Treatment Effect of Acupuncture in Different Outcomes: A Meta-Regression of Acupuncture Randomized Controlled Trials.
Wen-Cui XIU ; Wei-Juan GANG ; Qi ZHOU ; Lan-Jun SHI ; Xiang-Yu HU ; Tian-Yu MING ; Zhen LUO ; Yu-Qing ZHANG ; Xiang-Hong JING
Chinese journal of integrative medicine 2024;30(3):260-266
BACKGROUND:
The effects of acupuncture have varied in different randomized controlled trials (RCTs), and there are many factors that influence treatment effect of acupuncture in different outcomes, with conflicting results.
OBJECTIVE:
To identify factors and their impact on the treatment effect of acupuncture in different outcomes.
METHODS:
Acupuncture RCTs were searched from 7 databases including Medline (PubMed), Embase, Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure, Wanfang Database, VIP Database, and China Biology Medicine disc between January 1st, 2015 and December 31st, 2019. Eligible studies must compare acupuncture to no acupuncture, sham acupuncture, or waiting lists, and report at least 1 patient-important outcome. A multi-level meta-regression was conducted using a 3-level robust mixed model and univariate analyses were performed for all independent variables, even those excluded from the multivariable model due to collinearities. We used thresholds of 0.2 and 0.4 for the difference of standardized mean differences (SMDs), categorising them as small (<0.2), moderate (0.2-0.4), or large (>0.4) effects.
RESULTS:
The pain construct analysis involved 211 effect estimates from 153 studies and 14 independent variables. High-frequency acupuncture treatment sessions produced larger effects compared to low-frequency sessions [large magnitude, the difference of adjusted SMDs 0.46, 95% confidence interval (CI) 0.07 to 0.84; P=0.02]. The non-pain symptoms construct analysis comprised 323 effect estimates from 231 studies and 15 independent variables. Penetrating acupuncture showed moderately larger effects when compared to non-penetrating acupuncture (0.30, 95% CI 0.06 to 0.53; P=0.01). The function construct analysis included 495 effect estimates from 274 studies and 14 independent variables. Penetrating acupuncture and the flexible acupuncture regimen showed moderately larger effects, compared to non-penetrating acupuncture and fixed regimen, respectively (0.40, 95% CI 0 to 0.80; P=0.05; 0.29, 95% CI 0.06 to 0.53; P=0.01).
CONCLUSIONS
High-frequency acupuncture sessions appear to be a more effective approach to managing painful symptoms. Penetrating acupuncture demonstrated greater effect in relieving non-painful symptoms. Both penetrating acupuncture type and flexible acupuncture regimen were linked to significant treatment effects in function outcomes. Future studies should consider the factors that are significantly associated with the effects of acupuncture in patient-important outcomes.
Humans
;
Randomized Controlled Trials as Topic
;
Acupuncture Therapy/methods*
;
Pain
;
Pain Management
;
China
5.Status of wearable flexible monitoring devices based on organic field effect transistors in biomedical field
Kai GUO ; Cui-Zhi TANG ; Bo SUN ; Duan-Qiang XIAO ; Yuan-Biao LIU ; En-Xiang JIAO ; Jie GONG ; Hai-Jun ZHANG
Chinese Medical Equipment Journal 2024;45(1):93-100
The working principle and development of flexible semiconductor devices based on organic field effect transistor(OFET)technology were introduced.The current research status of OFET-based wearable flexible monitoring devices were reviewed,including biomechanical monitoring devices,tattoo biomonitoring devices and cellular detection devices and etc.The deficiencies of OFET-based wearable flexible monitoring devices were analyzed,and it's pointed out that miniaturization,personalization and diversification were the directions for the development of the future OFET-based wearable flexible moni-toring devices.[Chinese Medical Equipment Journal,2024,45(1):93-100]
6.Application of blended teaching based on teaching case library in standardized residency training in department of radiology
Minghui CAO ; Dongye WANG ; Jiaji MAO ; Xiang ZHANG ; Chushan ZHENG ; Guangzi SHI ; Haoyuan CUI ; Jun SHEN
Chinese Journal of Medical Education Research 2024;23(10):1436-1440
Objective:To investigate the teaching activity based on an online radiological teaching case library that integrates various teaching models including problem-based learning (PBL), case-based learning (CBL), flipped classroom, and microclass, as well as its application effect in standardized residency training in department of radiology.Methods:A total of 65 physicians who completed standardized residency training in Department of Radiology, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, from 2016 to 2022 were enrolled as subjects and were divided into control group with 32 physicians and experimental group with 33 physicians. The physicians in the control group received traditional teaching, and those in the experimental group received blended teaching with PBL, CBL, flipped classroom, and microclass based on a teaching case library. The two groups were compared in terms of the test scores of clinical thinking and decision making at the end of the course and their assessment and feedback for the teaching method. SPSS 22.0 was used to perform the t-test and the chi-square test. Results:For the assessment of clinical thinking and decision making, compared with the control group, the experimental group had significantly higher score of objective essay questions (49.83±1.27 vs. 48.74±1.64, P<0.05), score of subjective essay questions (39.57±1.75 vs. 36.02±1.81, P<0.05), and total score (89.40±1.54 vs. 84.76±1.93, P<0.05). The experimental group had significantly better assessment and feedback for the teaching method than the control group ( P<0.05). Conclusions:For physicians participating in standardized residency training, the blended teaching model based on teaching case library that integrates PBL, CBL, flipped classroom, and microclass can effectively improve the test scores of clinical thinking and decision making, stimulate their learning initiative and participation enthusiasm in medical imaging, and enhance their comprehensive ability for clinical diagnosis.
7.Safety and efficacy of the early administration of levosimendan in patients with acute non-ST-segment elevation myocardial infarction and elevated NT-proBNP levels: An Early Management Strategy of Acute Heart Failure (EMS-AHF).
Feng XU ; Yuan BIAN ; Guo Qiang ZHANG ; Lu Yao GAO ; Yu Fa LIU ; Tong Xiang LIU ; Gang LI ; Rui Xue SONG ; Li Jun SU ; Yan Ju ZHOU ; Jia Yu CUI ; Xian Liang YAN ; Fang Ming GUO ; Huan Yi ZHANG ; Qing Hui LI ; Min ZHAO ; Li Kun MA ; Bei An YOU ; Ge WANG ; Li KONG ; Jian Liang MA ; Xin Fu ZHOU ; Ze Long CHANG ; Zhen Yu TANG ; Dan Yu YU ; Kai CHENG ; Li XUE ; Xiao LI ; Jiao Jiao PANG ; Jia Li WANG ; Hai Tao ZHANG ; Xue Zhong YU ; Yu Guo CHEN
Chinese Journal of Internal Medicine 2023;62(4):374-383
Objectives: To investigated the safety and efficacy of treating patients with acute non-ST-segment elevation myocardial infarction (NSTEMI) and elevated levels of N-terminal pro-hormone B-type natriuretic peptide (NT-proBNP) with levosimendan within 24 hours of first medical contact (FMC). Methods: This multicenter, open-label, block-randomized controlled trial (NCT03189901) investigated the safety and efficacy of levosimendan as an early management strategy of acute heart failure (EMS-AHF) for patients with NSTEMI and high NT-proBNP levels. This study included 255 patients with NSTEMI and elevated NT-proBNP levels, including 142 males and 113 females with a median age of 65 (58-70) years, and were admitted in the emergency or outpatient departments at 14 medical centers in China between October 2017 and October 2021. The patients were randomly divided into a levosimendan group (n=129) and a control group (n=126). The primary outcome measure was NT-proBNP levels on day 3 of treatment and changes in the NT-proBNP levels from baseline on day 5 after randomization. The secondary outcome measures included the proportion of patients with more than 30% reduction in NT-proBNP levels from baseline, major adverse cardiovascular events (MACE) during hospitalization and at 6 months after hospitalization, safety during the treatment, and health economics indices. The measurement data parameters between groups were compared using the t-test or the non-parametric test. The count data parameters were compared between groups using the χ² test. Results: On day 3, the NT-proBNP levels in the levosimendan group were lower than the control group but were statistically insignificant [866 (455, 1 960) vs. 1 118 (459, 2 417) ng/L, Z=-1.25,P=0.21]. However, on day 5, changes in the NT-proBNP levels from baseline in the levosimendan group were significantly higher than the control group [67.6% (33.8%,82.5%)vs.54.8% (7.3%,77.9%), Z=-2.14, P=0.03]. There were no significant differences in the proportion of patients with more than 30% reduction in the NT-proBNP levels on day 5 between the levosimendan and the control groups [77.5% (100/129) vs. 69.0% (87/126), χ²=2.34, P=0.13]. Furthermore, incidences of MACE did not show any significant differences between the two groups during hospitalization [4.7% (6/129) vs. 7.1% (9/126), χ²=0.72, P=0.40] and at 6 months [14.7% (19/129) vs. 12.7% (16/126), χ²=0.22, P=0.64]. Four cardiac deaths were reported in the control group during hospitalization [0 (0/129) vs. 3.2% (4/126), P=0.06]. However, 6-month survival rates were comparable between the two groups (log-rank test, P=0.18). Moreover, adverse events or serious adverse events such as shock, ventricular fibrillation, and ventricular tachycardia were not reported in both the groups during levosimendan treatment (days 0-1). The total cost of hospitalization [34 591.00(15 527.46,59 324.80) vs. 37 144.65(16 066.90,63 919.00)yuan, Z=-0.26, P=0.80] and the total length of hospitalization [9 (8, 12) vs. 10 (7, 13) days, Z=0.72, P=0.72] were lower for patients in the levosimendan group compared to those in the control group, but did not show statistically significant differences. Conclusions: Early administration of levosimendan reduced NT-proBNP levels in NSTEMI patients with elevated NT-proBNP and did not increase the total cost and length of hospitalization, but did not significantly improve MACE during hospitalization or at 6 months.
Male
;
Female
;
Humans
;
Aged
;
Natriuretic Peptide, Brain
;
Simendan/therapeutic use*
;
Non-ST Elevated Myocardial Infarction
;
Heart Failure/drug therapy*
;
Peptide Fragments
;
Arrhythmias, Cardiac
;
Biomarkers
;
Prognosis
8.Acupuncture for in vitro fertilization-embryo transfer: an overview of systematic reviews.
Xiang-Yu HU ; Wen-Cui XIU ; Lan-Jun SHI ; Rui-Min JIAO ; Zi-Yu TIAN ; Xiao-Yi HU ; Tian-Yu MING ; Wei-Juan GANG ; Xiang-Hong JING
Chinese Acupuncture & Moxibustion 2023;43(11):1315-1323
OBJECTIVES:
To evaluate the report quality, methodological quality and evidence quality of the systematic reviews and meta-analyses (SRs/MAs) of acupuncture for in vitro fertilization-embryo transfer (IVF-ET).
METHODS:
The SRs/MAs of acupuncture for IVF-ET were searched electronically from databases of CNKI, Wanfang, VIP, SinoMed, PubMed, Embase, Cochrane Library, from inception of each database to September 27th, 2022. Two reviewers independently screened the literature and extracted the data. Using PRISMA statement, the AMSTAR 2 scale and the GRADE system, the report quality, methodological quality and evidence quality of the included SRs/MAs were assessed.
RESULTS:
A total of 28 SRs/MAs were included, with PRISMA scores ranging from 8.5 points to 27 points. The problems of report quality focused on protocol and registration, retrieval, risk of bias in studies, additional analysis, limitations and funding. The methodological quality of included studies was generally low, reflecting on items 2, 3, 7, 10, 12 and 16. A total of 85 outcome indexes were included in the GRADE system for evidence grade evaluation. Most of the evidences were low or very low in quality. The reasons for the downgrade were related to study limitations, inconsistency, imprecision and publication bias.
CONCLUSIONS
Acupuncture therapy improves the outcomes of IVF-ET, but the methodological quality and evidence quality of related SRs/MAs are low. It is recommended to conduct more high-quality studies in the future to provide more reliable evidences.
Acupuncture Therapy/methods*
;
Databases, Factual
;
Embryo Transfer
;
Fertilization in Vitro
;
Publication Bias
;
Systematic Reviews as Topic
9.Approach to Assess Adequacy of Acupuncture in Randomized Controlled Trials: A Systematic Review.
Lan-Jun SHI ; Zi-Yu TIAN ; Xiao-Yi HU ; Wen-Cui XIU ; Rui-Min JIAO ; Xiang-Yu HU ; Nicola ROBINSON ; Wei-Juan GANG ; Xiang-Hong JING
Chinese journal of integrative medicine 2023;29(8):730-737
OBJECTIVE:
To summarize and identify the available instruments/methods assessing the adequacy of acupuncture in randomized controlled trials (RCTs) for proposing a new improved instrument.
METHODS:
A systematic literature search was carried out in 7 electronic databases from inception until 21st November 2022. Any study evaluating the adequacy or quality of acupuncture, specifying specific acupuncture treatment-related factors as criteria of subgroup analysis, or developing an instrument/tool to assess the adequacy or quality of acupuncture in an RCT was included. Basic information, characteristics and contents of acupuncture adequacy assessment were presented as frequencies and percentages.
RESULTS:
Forty studies were included in this systematic review. Thirty-five studies (87.50%) were systematic reviews, none of which used formal methods to develop the assessment instruments/methods of acupuncture adequacy; of 5 methodological studies, only 1 study used a relatively formal method. Thirty-two studies (82.05%) assessed the components of acupuncture, while 7 (17.95%) assessed the overall quality of acupuncture. An independent assessment instrument/method was used to assess acupuncture adequacy in 29 studies (74.35%), whereas as one part of a methodological quality assessment scale in 10 (25.65%). Only 9 (23.00%) studies used the assessment results for subgroup analysis, sensitivity analysis or the criteria for inclusion in the meta-analysis.
CONCLUSION
Assessment contents for adequacy or quality of acupuncture in RCTs hadn't still reached consensus and no widely used assessment tools appeared. The methodology of available assessment instruments/scales is far from formal and rigorous. A new instrument/tool assessing adequacy of acupuncture should be developed using a formal method.
Acupuncture Therapy/methods*
;
Randomized Controlled Trials as Topic
10.Expert consensus on the prevention and treatment of adverse reactions in subcutaneous immunotherapy(2023, Chongqing).
Yu Cheng YANG ; Yang SHEN ; Xiang Dong WANG ; Yan JIANG ; Qian Hui QIU ; Jian LI ; Shao Qing YU ; Xia KE ; Feng LIU ; Yuan Teng XU ; Hong Fei LOU ; Hong Tian WANG ; Guo Dong YU ; Rui XU ; Juan MENG ; Cui Da MENG ; Na SUN ; Jian Jun CHEN ; Ming ZENG ; Zhi Hai XIE ; Yue Qi SUN ; Jun TANG ; Ke Qing ZHAO ; Wei Tian ZHANG ; Zhao Hui SHI ; Cheng Li XU ; Yan Li YANG ; Mei Ping LU ; Hui Ping YE ; Xin WEI ; Bin SUN ; Yun Fang AN ; Ya Nan SUN ; Yu Rong GU ; Tian Hong ZHANG ; Luo BA ; Qin Tai YANG ; Jing YE ; Yu XU ; Hua Bin LI
Chinese Journal of Otorhinolaryngology Head and Neck Surgery 2023;58(7):643-656

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