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.A strategy to reduce unnecessary prostate biopsies in patients with tPSA >10 ng ml -1 and PI-RADS 1-3.
Qi-Fei DONG ; Yi-Xun LIU ; Yu-Han CHEN ; Yi-Fan MA ; Tao ZHOU ; Xue-Feng FAN ; Xiang YU ; Chang-Ming WANG ; Jun XIAO
Asian Journal of Andrology 2025;27(4):531-536
We propose a strategy to reduce unnecessary prostate biopsies in Chinese patients with total prostate-specific antigen (tPSA) >10 ng ml -1 and Prostate Imaging Reporting and Data System (PI-RADS) scores between 1 and 3. Clinical data derived from 517 patients of The First Affiliated Hospital of USTC (Hefei, China) from January 2020 to December 2023 who met the screening criteria for the study were retrospectively collected. Independent predictors were identified via univariate and multivariate logistic regression analysis. The diagnostic capacity of clinical variables was evaluated using the receiver operating characteristic (ROC) curves and area under the curve (AUC). A prostate biopsy strategy was developed via risk stratification. Of the 517 patients, 17/348 (4.9%) with PI-RADS 1-2 were diagnosed with clinically significant prostate cancer (csPCa), and 27/169 (16.0%) patients with PI-RADS 3 were diagnosed with csPCa. The appropriate prostate-specific antigen density (PSAD) cut-off values were 0.45 ng ml -2 for PI-RADS 1-2 patients and 0.3 ng ml -2 for PI-RADS 3 patients. The appropriate prostate volume (PV) cut-off values were 40 ml for PI-RADS 1-2 patients and 50 ml for PI-RADS 3 patients. The prostate biopsy strategy based on PSAD and PV developed in this study can reduce unnecessary prostate biopsies in patients with tPSA >10 ng ml -1 and PI-RADS 1-3. In the study, 66.5% (344/517) patients did not need to undergo prostate biopsy, at the expense of missing only 1.7% (6/344) patients with csPCa.
Humans
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Male
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Prostatic Neoplasms/diagnostic imaging*
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Prostate-Specific Antigen/blood*
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Aged
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Middle Aged
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Retrospective Studies
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Prostate/diagnostic imaging*
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Unnecessary Procedures/statistics & numerical data*
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Biopsy/statistics & numerical data*
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China
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ROC Curve
3.The value of high-throughput sequencing data reanalysis in identifying ERBB2 amplification in colorectal cancer patients
Min-Na SHEN ; Li ZHANG ; Xin-Ning CHEN ; Fei HUANG ; Chao-Gang BAI ; Li-Meng CHEN ; Hai-Xiang PENG ; Yan ZHOU ; Bei-Li WANG ; Bai-Shen PAN ; Wei GUO
Fudan University Journal of Medical Sciences 2024;51(2):166-171
Objective To evaluate the value of high-throughput sequencing(HTS)data reanalysis that does not include ERBB2 copy number variation(CNV)analysis,in identifying ERBB2 amplification in patients with colorectal cancer.Methods The HTS data of 252 cases of colorectal cancer diagnosed by pathological biopsy who received peripheral blood cfDNA HTS detection samples were retrospectively analyzed.According to the HTS data of ERBB2 non-amplified samples judged by immunohistochemistry(IHC)and/or fluorescence in situ hybridization(FISH),the number of chromosome 17(Chr17)reads in the total number of reads was calculated the range of the ratio was initially determined as the threshold for prompting ERBB2 amplification.Suspected positive samples were screened according to thresholds and verified by digital PCR,IHC and FISH.Results The proportion of the number of Chr17 reads accounts for the number of total reads in the 89 cases of ERBB2 non-amplified samples determined by IHC and/or FISH ranged from 0.188 to 0.299(0.239±0.192).Using 0.298(1.25 times the mean)as the threshold indicating ERBB2 amplification,the data of 163 samples were analyzed,of which 7 cases were suspected to be positive,and the ratio ranged from 0.302 to 0.853.Among them,5 cases were determined to be positive by IHC and/or FISH,and 6 cases were confirmed to be positive by digital PCR.The ratio of the number of Chr17 reads to the number of total reads was positively correlated with the ratio of ERBB2/EIF2C1,and the correlation was good(r2=0.909).Conclusion The high-throughput sequencing data that does not cover the ERBB2 CNV analysis has a certain hint value for ERBB2 amplification in patients with colorectal cancer.
4.Analysis of Clinical Characteristics and Laboratory Indicators in Patients with Solid Malignant Tumor-Associated Venous Thromboembolism
Yong-Mei ZHOU ; Hai-Yan ZHANG ; Qing-Qing GUO ; Fang-Fang LOU ; Xiang-Hong ZHOU ; Fei RAN
Journal of Experimental Hematology 2024;32(3):847-851
Objective:To analyze the clinical features and laboratory indicators in patients with solid malignant tumor-associated venous thromboembolism(Ta-VTE),and to study the risk factors for Ta-VTE.Methods:The hospitalized patients with VTE in Guizhou Provincial People's Hospital from January to December 2020 were enrolled,and they were divided into Ta-VTE group and pure VTE group based on the presence or absence of solid malignant tumor.The differences in clinical data and laboratory indicators between the two groups were analyzed,and the indicators with significant differences were included in logistic regression model to analyze the risk factors of Ta-VTE.Results:A total of 288 patients with VTE were included in this study,including 64 cases in Ta-VTE group and 224 cases in pure VTE group,respectively.There were significant differences in the following indexes between the two groups,including the hospitalization time(14.20±15.29 d vs 10.05±6.90 d,t=3.112,P=0.002),pain(35.94%vs 65.18%,x2=17.554,P=0.000),recent surgery(75.00%vs 37.50%,X2=28.196,P=0.000),D-dimer[2.8(0.92,7.55)μg/ml vs 5.69(2.25,13.91)μg/ml,Z=-2.710,P=0.007],PLR[198.59(139.54,312.16)vs 149.76(114.08,233.66),Z=-2.924,P=0.003]and TBIL[10.90(7.63,15.68)μmol/Lvs 12.90(9.33,18.28)μmol/L,Z=-2.066,P=0.039].There was no significant difference in the other indicators(P>0.05).The result of multivariate logistic regression analysis showed that elevated PLR(OR=1.003,95%CI:1.000-1.006,P=0.027),recent surgery(OR=4.312,95%CI:2.093-8.885,P=0.000)and prolonged hospitalization(OR=1.037,95%CI:1.002-1.074,P=0.038)were independent risk factors for Ta-VTE.However,pain(OR=0.274,95%CI:0.133-0.564,P=0.000)was a protective factor.Conclusion:Elevated PLR level,recent surgery and prolonged hospital stay are independent risk factors for Ta-VTE patients,and rational use of these indicators is helpful for the clinical diagnosis and treatment of Ta-VTE patients.
5.Comparison of Two Methods With a Left-Sided Double-Lumen Tube for Endobronchial Intubation
Huiying ZHOU ; Yuda FEI ; Xiang QUAN
Acta Academiae Medicinae Sinicae 2024;46(1):39-42
Objective To compare the success rates of two methods for endobronchial intubation:the left-sided double-lumen tube(DLT)rotated 90° counter-clockwise with the patient head at the mid positon and the tube rotated 180°counter-clockwise with the patient head turned to the right.Methods Six hundred and forty-eight patients were enrolled in this study,who were to undergo elective thoracic surgery by left-sided DLT intuba-tion in the Peking Union Medical College Hospital from December 2021 to June 2022.They were randomized into a 90° group and a 180° group,with 324 patients in each group.In the 90° group,with the patient head kept at the mid position,the left-sided DLT was advanced until the bronchial cuff passed the vocal cords and then rotated 90° counter-clockwise.In the 180°group,with the left mandible angle of each patient in the straight line with the ster-num,the tube was advanced until the bronchial cuff passed the vocal cords and then rotated 180° counter-clock-wise.The intubation success rate and the intubation-related complications such as carina mucosal injuries were com-pared between the two groups.Results The 648 patients included 336 males and 312 females,with the age ran-ging from 39.0 to 75.0 years old and the average age of(54.6±9.0)years old.The success rate of first intubation was 80.3% in the 90°group and 75.0% in the 180°group,which showed no significant difference(P =0.109).The success rate of second intubation was higher in the 180°group than in the 90°group(P<0.001).The rate of carina mucosal injuries was 23.8% in the 90° group and 25.6% in the 180° group,which showed no significant difference(P =0.585).Conclusions Compared with the conventional method(90°),the intubation of the left-sided DLT rotated 180° counter-clockwise with the patient head turned to the right cannot improve the success rate of the first intubation.However,it could improve the success rate of reintubation as a remedy.
6.Contrast-Enhanced Ultrasound in the Differential Diagnosis of Gallbladder Polypoid Lesions:A Multicenter Study
Ligang JIA ; Xiang FEI ; Xiang JING ; Mingxing LI ; Fang NIE ; Dong JIANG ; Shaoshan TANG ; Wei ZHANG ; Hong DING ; Tao SONG ; Qi ZHOU ; Bei ZHANG ; Zhixia SUN ; Xiaojuan MA ; Nianan HE ; Fang LI ; Yingqiao ZHU ; Wen CHENG ; Yukun LUO
Chinese Journal of Medical Imaging 2024;32(11):1147-1154
Purpose To explore the value of contrast-enhanced ultrasound(CEUS)in the differential diagnosis of gallbladder polypoid lesions(GPLs)(diameter≥10 mm).Materials and Methods A prospective enrollment of 229 patients with GPLs who underwent cholecystectomy in 17 hospitals from December 1 2021 to June 30 2024 was conducted to analyze the relationship between general data,conventional ultrasound,CEUS characteristics and the nature of GPLs.Multivariate Logistic regression was employed to identify independent risk factors for neoplastic polyps,the differential diagnostic value of different indicators was compared.Results Among 229 patients with GPLs,there were 108 cases of cholesterol polyps,102 cases of adenoma and 19 cases of gallbladder cancer.Age(Z=-4.476,P<0.001),polyp number(χ2=15.561,P<0.001),diameter(Z=-8.149,P<0.001),echogenicity(χ2=9.241,P=0.010),vascularity(χ2=23.107,P<0.001),enhancement intensity(χ2=47.610,P<0.001),enhancement pattern(χ2=6.468,P=0.011),vascular type(χ2=84.470,P<0.001),integrity of gallbladder wall(χ2=7.662,P=0.006)and stalk width(Z=-9.831,P<0.001)between cholesterol polyps and neoplastic polyps were statistically significant.Age,location,diameter,echogenicity,enhancement pattern,vascular type and stalk width between adenoma and gallbladder cancer were statistically significant(Z=-4.333,-3.902,-5.042,all P<0.05).Multivariate Logistic regression analysis showed that hyper-enhancement,branched vascular type and stalk width were independent risk factors for neoplastic polyps(OR=4.563,5.770,3.075,all P<0.001).The combination of independent risk factors was better than single factor and diameter in the differential diagnosis of cholesterol polyps and neoplastic polyps(all P<0.01).Conclusion CEUS can effectively identify the nature of GPLs and provide a valuable imaging reference for the selection of treatment methods.
7.An advanced machine learning method for simultaneous breast cancer risk prediction and risk ranking in Chinese population: A prospective cohort and modeling study
Liyuan LIU ; Yong HE ; Chunyu KAO ; Yeye FAN ; Fu YANG ; Fei WANG ; Lixiang YU ; Fei ZHOU ; Yujuan XIANG ; Shuya HUANG ; Chao ZHENG ; Han CAI ; Heling BAO ; Liwen FANG ; Linhong WANG ; Zengjing CHEN ; Zhigang YU
Chinese Medical Journal 2024;137(17):2084-2091
Background::Breast cancer (BC) risk-stratification tools for Asian women that are highly accurate and can provide improved interpretation ability are lacking. We aimed to develop risk-stratification models to predict long- and short-term BC risk among Chinese women and to simultaneously rank potential non-experimental risk factors.Methods::The Breast Cancer Cohort Study in Chinese Women, a large ongoing prospective dynamic cohort study, includes 122,058 women aged 25-70 years old from the eastern part of China. We developed multiple machine-learning risk prediction models using parametric models (penalized logistic regression, bootstrap, and ensemble learning), which were the short-term ensemble penalized logistic regression (EPLR) risk prediction model and the ensemble penalized long-term (EPLT) risk prediction model to estimate BC risk. The models were assessed based on calibration and discrimination, and following this assessment, they were externally validated in new study participants from 2017 to 2020.Results::The AUC values of the short-term EPLR risk prediction model were 0.800 for the internal validation and 0.751 for the external validation set. For the long-term EPLT risk prediction model, the area under the receiver operating characteristic curve was 0.692 and 0.760 in internal and external validations, respectively. The net reclassification improvement index of the EPLT relative to the Gail and the Han Chinese Breast Cancer Prediction Model (HCBCP) models for external validation was 0.193 and 0.233, respectively, indicating that the EPLT model has higher classification accuracy.Conclusions::We developed the EPLR and EPLT models to screen populations with a high risk of developing BC. These can serve as useful tools to aid in risk-stratified screening and BC prevention.
8.Mechanism of carvacrol on inhibiting biofilm formation of hypervirulent Klebsiella pneumoniae
Chun-Ping WEI ; Tian-Xin XIANG ; Yang LIU ; Na CHENG ; Fei HAN ; Li ZHOU ; Peng LIU ; Dan-Dan WEI
Chinese Journal of Infection Control 2024;23(7):833-839
Objective To explore the potential mechanism of carvacrol on inhibiting the formation of biofilm of hy-pervirulent Klebsiella pneumoniae(hvKP).Methods The possible mechanisms of carvacrol were analyzed based on the detection of its effects on the formation and morphology of biofilms,changes in extracellular polysaccharide and capsule polysaccharide content,as well as changes in the expression levels of biofilm-related genes rmpA2,mag A,mrkA,mrkB,and treC of hvKP.Results The minimum inhibitory concentration of carvacrol on hvKP was 512 μg/mL,with an obvious inhibitory effect on the biofilm formation of hvKP,presenting a concentration-depen-dent effect.Under the scanning electron microscope,it was observed that the biofilm structure was loose and the in-tercellular connections were not dense under the intervention of carvacrol.The Congo Red adsorption test and m-hydroxybiphenyl colorimetric method showed that carvacrol could reduce the content of capsule polysaccharides of hvKP,but didn't affect the total extracellular polysaccharide content.Fluorescence quantitative polymerase chain reaction(PCR)showed that under the effect of carvacrol at sub-inhibitory concentration,the synthesis of capsule polysaccharide,expression levels of sugar transport system and pili adhesion-related genes all decreased by more than 50%.Conclusion Carvacrol has a significant inhibitory effect on the formation of biofilm in hvKP,and its mechanism may be related to the decrease of synthesis of capsule polysaccharide as well as expression of biofilm-re-lated genes,such as sugar transport system and pili adhesion.
9.Survey on the current status of Helicobacter pylori infection and related risk factors in Haikou city
Xiao-Dong ZHANG ; Da-Ya ZHANG ; Shi-Ju CHEN ; Run-Xiang CHEN ; Yan ZHOU ; Ling WEI ; Chang-Jiang LIU ; Yun-Qian XIE ; Fei-Hu BAI
Modern Interventional Diagnosis and Treatment in Gastroenterology 2024;29(4):393-397
Objective To explore the relevant risk factors of H.pylori infection,and provide reference for prevention and treatment of H.pylori in this area,and further provide theoretical basis for the prevention and treatment of gastric cancer.Methods A total of 1200 residents in four districts of Haikou city were investigated by questionnaire and urea 14 C breath test by holistic stratified random sampling to calculate the population infection rate and analyze the risk factors of infection.Results The total infection rate was 32.5%,which was lower than the national H.pylori infection rate.No consumption of fruits and vegetables,no habit of washing hands before meals,and people with gastrointestinal symptoms,are independent risk factors of H.pylori infection.No consumption of pickled products is of great significance to prevent H.pylori infection.Conclusion The prevalence of H.pylori infection in the population of Haikou is lower than the national average,and H.pylori infection is closely related to the poor living habits of residents.
10.Fast identification of origins and cultivation patterns of Astragali Radix by dimension reduction algorithms of hyperspectral data.
Fei-Xiang ZHOU ; Hong JIANG ; Bao-Lin GUO ; Jiao-Yang LUO ; Cheng PAN ; Mei-Hua YANG ; Ye-Lin LIU
China Journal of Chinese Materia Medica 2024;49(24):6660-6666
This study aims to establish a rapid and non-destructive method for recognizing the origins and cultivation patterns of Astragali Radix. A hyperspectral imaging system(spectral ranges: 400-1 000 nm, 900-1 700 nm; detection time: 15 s) was used to examine the samples of Astragali Radix with different origins and cultivation patterns. The collected hyperspectral datasets were highly correlated and numerous, which required the establishment of stable and reliable dimension reduction and classification models. Firstly, the original spectra were preprocessed by normalization, Gaussian smoothing, and masking. Then, principal component analysis(PCA), partial least squares-discriminant analysis(PLS-DA), and competitive adaptive reweighted sampling(CARS) were performed to reduce the dimension of the hyperspectral data. Finally, support vector machine(SVM), feedforward neural network(FFNN), and convolutional neural network(CNN) were used for data training of the spectral images and spectral curves with dimension reduction. The results showed that applying CARS as a variable selection method before PLS-DA on the hyperspectral data of Astragali Radix achieved the accuracy, precision, and recall of 100% on the CNN test dataset. The F_1-score and area under the curve of ROC(AUC) reached 1. This method is convenient, quick, sample-saving, and non-destructive, providing technical support for rapid identification of the origins and cultivation patterns of Astragali Radix.
Drugs, Chinese Herbal/chemistry*
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Neural Networks, Computer
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Algorithms
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Support Vector Machine
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Principal Component Analysis
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Discriminant Analysis
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Hyperspectral Imaging/methods*
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Least-Squares Analysis
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Astragalus Plant/growth & development*
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Astragalus propinquus/growth & development*

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