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.Characteristics analysis of OSA patients in different age groups based on 10 years of PSG monitoring
Lili PENG ; Jinrang LI ; Zhi LIU ; Chun ZHANG ; Shizhen ZOU ; Wei YUAN ; Leilei YU ; Yuanyuan JIA
Chinese Journal of Otorhinolaryngology Head and Neck Surgery 2025;60(9):1127-1133
Objective:A retrospective analysis was conducted on the clinical characteristics and polysomnography (PSG) features of patients with obstructive sleep apnea (OSA) of different ages.Methods:From January 2015 to March 2024, the patients who underwent overnight PSG monitoring at the Sleep Respiratory Disease Diagnosis and Treatment Center, Department of Otolaryngology, Head and Neck Surgery, Sixth Medical Center of the PLA General Hospital were sequentially enrolled.A total of 4 396 patients[aged from 18 to 97(46.04±12.60)years] with OSA who met the criteria were finally enrolled and divided into the youth group (18-44 years old, n=2 099), middle-aged group (45-59 years old, n=1 641), and elderly group (≥60 years old, n=656).The differences in general condition, Epworth sleepiness Scale (ESS) score, rapid eye movement sleep (REM) sleep time in total sleep time, micro-awakening index, apnea hypopnea index (AHI), minimum oxygen saturation at night (LSpO 2), oxygen hypoxia index (ODI) and so on were compared.Multivariate Logistic regression was used to analyze the relationship between age stratification and different severity of OSA (mild 5≤AHI≤15, moderate 15
3.Research of Subtype A Caused by New A Allele Mutation
Li-Ping ZOU ; Fang QIU ; Jian-Shuo LIU ; Zhi-Peng WU ; Feng-Qing ZHANG ; Ying ZHU
Journal of Experimental Hematology 2025;33(6):1765-1768
Objective:In order to clarify the ABO phenotype and genotype,and explore the molecular biological mechanism,serological detection,genotyping and gene sequencing were performed on an upper gastrointestinal hemorrhage patient with inconsistent forward and reverse ABO blood typing.Methods:ABO forward and reverse blood typing,H antigen identification,capillary centrifugation test and salivary substance detection were performed by classical serological method,moreover,polymerase chain reaction-sequence specific primer(PCR-SSP)was used for ABO genotyping,ABO gene 1-7 exons were sequenced by Sanger analysis in order to identify mutation.Results:Mixed field agglutination with anti-A,anti-AB and no agglutination with anti-A1 were appeared in the forward typing tests,agglutination with B cells but no agglutination with A1 cells and O cells were appeared in the reverse typing tests.3+agglutination strength was showed with anti-H.In capillary centrifugation experiment,erythrocyte after isolation in proximal part and distal end had same strength of agglutination with anti-A.Substances A and H were detected in saliva.The patient was assigned an A3 phenotype according to serological characteristics.Sequencing results of ABO gene 1-7 exons showed c.261delG,c.467C>T,c.865A>G,in which,865A>G was the first discovered mutation,and this new mutation had been submitted to GenBank with accession number PP187306.Conclusion:A novel site mutation c.865A>G is reported in this study,and this new mutation can result in a replacement of Met with Val at residue 289(p.Met289Val)and lead to an A3 phenotype.
4.Research of Subtype A Caused by New A Allele Mutation
Li-Ping ZOU ; Fang QIU ; Jian-Shuo LIU ; Zhi-Peng WU ; Feng-Qing ZHANG ; Ying ZHU
Journal of Experimental Hematology 2025;33(6):1765-1768
Objective:In order to clarify the ABO phenotype and genotype,and explore the molecular biological mechanism,serological detection,genotyping and gene sequencing were performed on an upper gastrointestinal hemorrhage patient with inconsistent forward and reverse ABO blood typing.Methods:ABO forward and reverse blood typing,H antigen identification,capillary centrifugation test and salivary substance detection were performed by classical serological method,moreover,polymerase chain reaction-sequence specific primer(PCR-SSP)was used for ABO genotyping,ABO gene 1-7 exons were sequenced by Sanger analysis in order to identify mutation.Results:Mixed field agglutination with anti-A,anti-AB and no agglutination with anti-A1 were appeared in the forward typing tests,agglutination with B cells but no agglutination with A1 cells and O cells were appeared in the reverse typing tests.3+agglutination strength was showed with anti-H.In capillary centrifugation experiment,erythrocyte after isolation in proximal part and distal end had same strength of agglutination with anti-A.Substances A and H were detected in saliva.The patient was assigned an A3 phenotype according to serological characteristics.Sequencing results of ABO gene 1-7 exons showed c.261delG,c.467C>T,c.865A>G,in which,865A>G was the first discovered mutation,and this new mutation had been submitted to GenBank with accession number PP187306.Conclusion:A novel site mutation c.865A>G is reported in this study,and this new mutation can result in a replacement of Met with Val at residue 289(p.Met289Val)and lead to an A3 phenotype.
5.Characteristics analysis of OSA patients in different age groups based on 10 years of PSG monitoring
Lili PENG ; Jinrang LI ; Zhi LIU ; Chun ZHANG ; Shizhen ZOU ; Wei YUAN ; Leilei YU ; Yuanyuan JIA
Chinese Journal of Otorhinolaryngology Head and Neck Surgery 2025;60(9):1127-1133
Objective:A retrospective analysis was conducted on the clinical characteristics and polysomnography (PSG) features of patients with obstructive sleep apnea (OSA) of different ages.Methods:From January 2015 to March 2024, the patients who underwent overnight PSG monitoring at the Sleep Respiratory Disease Diagnosis and Treatment Center, Department of Otolaryngology, Head and Neck Surgery, Sixth Medical Center of the PLA General Hospital were sequentially enrolled.A total of 4 396 patients[aged from 18 to 97(46.04±12.60)years] with OSA who met the criteria were finally enrolled and divided into the youth group (18-44 years old, n=2 099), middle-aged group (45-59 years old, n=1 641), and elderly group (≥60 years old, n=656).The differences in general condition, Epworth sleepiness Scale (ESS) score, rapid eye movement sleep (REM) sleep time in total sleep time, micro-awakening index, apnea hypopnea index (AHI), minimum oxygen saturation at night (LSpO 2), oxygen hypoxia index (ODI) and so on were compared.Multivariate Logistic regression was used to analyze the relationship between age stratification and different severity of OSA (mild 5≤AHI≤15, moderate 15
6.Prediction and identification of B-cell epitopes of SARS-CoV-2 E protein
Peng-Fei ZHANG ; Jun LIU ; Zi-Yang ZOU ; Xi-Long KANG ; Li SONG ; Xin-An JIAO ; Chuang MENG ; Zhi-Ming PAN
Chinese Journal of Zoonoses 2024;40(9):807-813
This work was aimed at predicting and verifying B-cell epitopes of SARS-CoV-2 E protein through bioinformatics methods,and clarifying the dominant B cell epitopes with mouse polyclonal antibody serum prepared through SARS-CoV-2 re-combinant E protein immunization and human positive serum vaccinated with inactivated SARS-CoV-2 vaccine.The structural and B-cell linear epitopes of SARS-CoV-2 E protein were predicted with SOPMA,Expasy,SWISS-MODEL,IEDB database,and Bepid-2.0 software.Candidate epitopes were expressed as GST-tagged recombinant protein fragments in an E.coli sys-tem,and their immunoreactivity with mouse and human poly-clonal positive serum against SARS-CoV-2 E protein was de-tected by western blotting and indirect ELISA,respectively.The epitope prediction results showed that E protein contained linear B cell epitopes Ser6-Val14 and Tyr57-Pro71,and the conformational epitopes of Glu8-Val12,Leu39-Tyr59,and Ser60-Leu65.The GST tagged recombinant E protein fragments of E1 and E3,containing Ser6-Val14 and Tyr57-Pro71 epitopes,respectively,as well as E2 without an epitope sequence as a control,were expressed in an E.coli expression system and successfully purified with an Ni-NTA column.Western blotting and indirect ELISA analysis indicated that all mouse and human SARS-CoV-2 positive sera positively reacted with only E1 and E3 proteins,but negatively reacted with E2 protein,thus indicating that the corresponding epitope prediction with Ser6-Val14 and Tyr57-Pro71 was correct.This study successfully predicted and preliminarily identified two linear B cell epitopes of SARS-CoV-2 E protein,thus providing a reference for the preparation of new coronavirus vaccines and the analysis of immune response characteristics.
7.Research progress on the protective effect and mechanism of puerarin on diabetic retinopathy
Hua ZOU ; Zhi-Peng YOU ; Xiao-Jian WU
International Eye Science 2023;23(8):1295-1298
Increasing prevalence and incidence of diabetes mellitus(DM)-the most common chronic consumptive disease worldwide-has a devastating impact on people's daily lives, particularly through the deterioration or complete loss of vision brought on by diabetic retinopathy(DR). Therefore, it is imperative to investigate the pathogenesis and effective treatment of DR. Meanwhile, Pueraria lobata is the extensively used dried root of kudzu or dried kudzu, also known as Pueraria flavonoids. Moreover, its roots are primarily composed of isoflavones, Pueroside ABC, triterpenes, and alkaloids, which can calm cardio-cerebrovascular smooth muscle and enhance microcirculation. Currently, it is widely employed for the treatment of cardio-cerebrovascular diseases, osteonecrosis, DM and its complications, neurodegenerative disorders, endometriosis and tumor diseases. Inhibiting retinal neovascularization, alleviating ischemia and hypoxia, decreasing advanced glycation end products in diabetes, raising insulin-like growth factor(IGF)expression while decreasing tumor necrosis factor-α(TNF-a)expression, decreasing vascular endothelial growth factor(VEGF)expression, reducing retinal nerve cell death, inhibiting the NOD-like receptor protein 3(NLRP3)inflammatory pathway and inhibiting ferroptosis are all mechanisms by which puerarin(Pue)has been found to protect the retina in recent studies. Thus, this article summarizes the current comprehension of the mechanism and protective effect of Pue on diabetic retina, serving as a guidepost for its future development and application.
8.Epidemiological characteristics of a 2019-nCoV outbreak caused by Omicron variant BF.7 in Shenzhen.
Yan Peng CHENG ; Dong Feng KONG ; Jia ZHANG ; Zi Quan LYU ; Zhi Gao CHEN ; Hua Wei XIONG ; Yan LU ; Qing Shan LUO ; Qiu Ying LYU ; Jin ZHAO ; Ying WEN ; Jia WAN ; Fang Fang LU ; Jian Hua LU ; Xuan ZOU ; Zhen ZHANG
Chinese Journal of Epidemiology 2023;44(3):379-385
Objective: To explore the epidemiological characteristic of a COVID-19 outbreak caused by 2019-nCoV Omicron variant BF.7 and other provinces imported in Shenzhen and analyze transmission chains and characteristics. Methods: Field epidemiological survey was conducted to identify the transmission chain, analyze the generation relationship among the cases. The 2019-nCoV nucleic acid positive samples were used for gene sequencing. Results: From 8 to 23 October, 2022, a total of 196 cases of COVID-19 were reported in Shenzhen, all the cases had epidemiological links. In the cases, 100 were men and 96 were women, with a median of age, M (Q1, Q3) was 33(25, 46) years. The outbreak was caused by traverlers initial cases infected with 2019-nCoV who returned to Shenzhen after traveling outside of Guangdong Province.There were four transmission chains, including the transmission in place of residence and neighbourhood, affecting 8 persons, transmission in social activity in the evening on 7 October, affecting 65 persons, transmission in work place on 8 October, affecting 48 persons, and transmission in a building near the work place, affecting 74 persons. The median of the incubation period of the infection, M (Q1, Q3) was 1.44 (1.11, 2.17) days. The incubation period of indoor exposure less than that of the outdoor exposure, M (Q1, Q3) was 1.38 (1.06, 1.84) and 1.95 (1.22, 2.99) days, respcetively (Wald χ2=10.27, P=0.001). With the increase of case generation, the number and probability of gene mutation increased. In the same transmission chain, the proportion of having 1-3 mutation sites was high in the cases in the first generation. Conclusions: The transmission chains were clear in this epidemic. The incubation period of Omicron variant BF.7 infection was shorter, the transmission speed was faster, and the gene mutation rate was higher. It is necessary to conduct prompt response and strict disease control when epidemic occurs.
Male
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Humans
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Female
;
SARS-CoV-2
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COVID-19/epidemiology*
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Disease Outbreaks
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Epidemics
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China/epidemiology*
9.Efficacy of partial nephrectomy in patients with localized renal carcinoma: a 20-year experience of 2 046 patients in a single center.
Xiang Peng ZOU ; Kang NING ; Zhi Ling ZHANG ; Long Bin XIONG ; Yu Lu PENG ; Zhao Hui ZHOU ; Yi Xin HUANG ; Xin LUO ; Ji Bin LI ; Pei DONG ; Sheng Jie GUO ; Hui HAN ; Fang Jian ZHOU
Chinese Journal of Surgery 2023;61(5):395-402
Objectives: To analyze the long-term survival of patients with localized renal cell carcinoma after partical nephrectomy. Methods: The clinicopathological records and survival follow-up data of 2 046 patients with localized renal cell carcinoma, who were treated with partial nephrectomy from August 2001 to February 2021 in the Department of Urology, Sun Yat-sen University Cancer Center, were retrospectively analyzed. There were 1 402 males and 644 females, aged (M(IQR)) 51 (19) years (range: 6 to 86 years). The primary end point of this study was cancer-specific survival. Survival curves were estimated using the Kaplan-Meier method, and the difference test was performed by Log-rank test. Univariate and multivariate Cox analysis were fitted to determine factors associated with cancer-specific survival. Results: The follow-up time was 49.2 (48.0) months (range: 1 to 229 months), with 1 974 patients surviving and 72 dying. The median cancer-specific survival time has not yet been reached. The 5- and 10-year cancer specific survival rates were 97.0% and 91.2%, respectively. The 10-year cancer-specific survival rates for stage pT1a (n=1 447), pT1b (n=523) and pT2 (n=58) were 95.3%, 81.8%, and 81.7%, respectively. The 10-year cancer-specific survival rates of patients with nuclear grade 1 (n=226), 2 (n=1 244) and 3 to 4 (n=278) were 96.6%, 89.4%, and 85.5%, respectively. There were no significant differences in 5-year cancer-specific survival rates among patients underwent open, laparoscopic, or robotic surgery (96.7% vs. 97.1% vs. 97.5%, P=0.600). Multivariate analysis showed that age≥50 years (HR=3.93, 95%CI: 1.82 to 8.47, P<0.01), T stage (T1b vs. T1a: HR=3.31, 95%CI: 1.83 to 5.99, P<0.01; T2+T3 vs. T1a: HR=2.88, 95%CI: 1.00 to 8.28, P=0.049) and nuclear grade (G3 to 4 vs. G1: HR=2.81, 95%CI: 1.01 to 7.82, P=0.048) were independent prognostic factors of localized renal cell carcinoma after partial nephrectomy. Conclusions: The long-term cancer-specific survival rates of patients with localized renal cancer after partial nephrectomy are satisfactory. The type of operation (open, laparoscopic, or robotic) has no significant effect on survival. However, patients with older age, higher nuclear grade, and higher T stage have a lower cancer-specific survival rate. Grasping surgical indications, attaching importance to preoperative evaluation, perioperative management, and postoperative follow-up, could benefit achieving satisfactory long-term survival.
10.Establishment and validation of a novel nomogram to predict overall survival after radical nephrectomy.
Long Bin XIONG ; Xiang Peng ZOU ; Kang NING ; Xin LUO ; Yu Lu PENG ; Zhao Hui ZHOU ; Jun WANG ; Zhen LI ; Chun Ping YU ; Pei DONG ; Sheng Jie GUO ; Hui HAN ; Fang Jian ZHOU ; Zhi Ling ZHANG
Chinese Journal of Oncology 2023;45(8):681-689
Objective: To establish a nomogram prognostic model for predicting the 5-, 10-, and 15-year overall survival (OS) of non-metastatic renal cell carcinoma patients managed with radical nephrectomy (RN), compare the modelled results with the results of pure pathologic staging, the Karakiewicz nomogram and the Mayo Clinic Stage, Size, Grade, and Necrosis (SSIGN) score commonly used in foreign countries, and stratify the patients into different prognostic risk subgroups. Methods: A total of 1 246 non-metastatic renal cell carcinoma patients managed with RN in Sun Yat-sen University Cancer Center (SYSUCC) from 1999 to 2020 were retrospectively analyzed. Multivariate Cox regression analysis was used to screen the variables that influence the prognosis for nomogram establishment, and the bootstrap random sampling was used for internal validation. The time-receiver operating characteristic curve (ROC), the calibration curve and the clinical decision curve analysis (DCA) were applied to evaluate the nomogram. The prediction efficacy of the nomogram and that of the pure pathologic staging, the Karakiewicz nomogram and the SSIGN score was compared through the area under the curve (AUC). Finally, patients were stratified into different risk subgroups according to our nomogram scores. Results: A total of 1 246 patients managed with RN were enrolled in this study. Multivariate Cox regression analysis showed that age, smoking history, pathological nuclear grade, sarcomatoid differentiation, tumor necrosis and pathological T and N stages were independent prognostic factors for RN patients (all P<0.05). A nomogram model named SYSUCC based on these factors was built to predict the 5-, 10-, and 15-year survival rate of the participating patients. In the bootstrap random sampling with 1 000 iterations, all these factors occurred for more than 800 times as independent predictors. The Harrell's concordance index (C-index) of SYSUCC was higher compared with pure pathological staging [0.770 (95% CI: 0.716-0.823) vs 0.674 (95% CI: 0.621-0.728)]. The calibration curve showed that the survival rate as predicted by the SYSUCC model simulated the actual rate, while the clinical DCA showed that the SYSUCC nomogram has a benefit in certain probability ranges. In the ROC analysis that included 857 patients with detailed pathological nuclear stages, the nomogram had a larger AUC (5-/10-year AUC: 0.823/0.804) and better discriminating ability than pure pathological staging (5-/10-year AUC: 0.701/0.658), Karakiewicz nomogram (5-/10-year AUC: 0.772/0.734) and SSIGN score (5-/10-year AUC: 0.792/0.750) in predicting the 5-/10-year OS of RN patients (all P<0.05). In addition, the AUC of the SYSUCC nomogram for predicting the 15-year OS (0.820) was larger than that of the SSIGN score (0.709), and there was no statistical difference (P<0.05) between the SYSUCC nomogram, pure pathological staging (0.773) and the Karakiewicz nomogram (0.826). The calibration curve was close to the standard curve, which indicated that the model has good predictive performance. Finally, patients were stratified into low-, intermediate-, and high-risk subgroups (738, 379 and 129, respectively) according to the SYSUCC nomogram scores, among whom patients in intermediate- and high-risk subgroups had a worse OS than patients in the low-risk subgroup (intermediate-risk group vs. low-risk group: HR=4.33, 95% CI: 3.22-5.81, P<0.001; high-risk group vs low-risk group: HR=11.95, 95% CI: 8.29-17.24, P<0.001), and the high-risk subgroup had a worse OS than the intermediate-risk group (HR=2.63, 95% CI: 1.88-3.68, P<0.001). Conclusions: Age, smoking history, pathological nuclear grade, sarcomatoid differentiation, tumor necrosis and pathological stage were independent prognostic factors for non-metastasis renal cell carcinoma patients after RN. The SYSUCC nomogram based on these independent prognostic factors can better predict the 5-, 10-, and 15-year OS than pure pathological staging, the Karakiewicz nomogram and the SSIGN score of patients after RN. In addition, the SYSUCC nomogram has good discrimination, agreement, risk stratification and clinical application potential.
Humans
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Nomograms
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Retrospective Studies
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Carcinoma, Renal Cell/pathology*
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Prognosis
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Risk Factors
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Nephrectomy
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Kidney Neoplasms/pathology*
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Necrosis

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