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.Prescription pattern of traditional Chinese medicine for treatment of hypertensive left ventricular hypertrophy based on multivariate data mining.
Xuan-Yang WANG ; Yuan GAO ; Bin LI ; Rui YU ; Shi-Yang XIE ; Lu-Ye ZHOU ; Yu-Die SUN ; Ming-Jun ZHU
China Journal of Chinese Materia Medica 2025;50(6):1688-1698
This study explored the prescription pattern of traditional Chinese medicine(TCM) in the treatment of hypertensive left ventricular hypertrophy(LVH), so as to provide a relevant theoretical basis for the clinical diagnosis and treatment of hypertensive LVH. The study systematically searched the databases of CNKI, Wanfang, VIP, and SinoMed to screen out the qualified literature on TCM treatment of hypertensive LVH and used Microsoft Excel 2021 to establish the relevant prescription database. It also counted the frequency, property, flavor, and meridian affiliation of TCM in the prescriptions and classified their efficacy. The study used Lantern 5.0 and Rstudio software to analyze the hidden structural models and association rules of the high-frequency TCM with a frequency of >3.50% and adopted Origin 2024 software to visualize the data, so as to explore the prescription pattern of TCM in treating hypertensive LVH. The results showed that a total of 128 TCM prescriptions were included, involving 163 TCM with a total frequency of 1 242. The high-frequency TCM included Salviae Miltiorrhizae Radix et Rhizoma, Uncariae Ramulus Cum Uncis, Gastrodiae Rhizoma, Poria, and Chuanxiong Rhizoma, with the main efficacy from blood-activating and stasis-resolving herbs, tonic herbs, and liver-calming and wind-extinguishing herbs. The latent structure analysis(LSA) identified 10 latent variables, 20 latent classes, 7 comprehensive clustering models, and 23 core prescriptions. It was speculated that the common syndromes of hypertensive LVH included blood stasis obstructing the collaterals, ascending hyperactivity of liver Yang, Yin deficiency with Yang hyperactivity, and intermingled phlegm and blood stasis. The association rule analysis yielded 33 strong association rules, with the highest comprehensive association rule being Gastrodiae Rhizoma→Uncariae Ramulus Cum Uncis. Hypertensive LVH is characterized by asthenia in origin and asthenia in superficiality, with Yin deficiency and Qi deficiency as the origin and blood stasis and phlegm as the superficiality. Clinical treatment focuses on activating blood circulation, resolving stasis, tonifying Qi, and nourishing Yin, combined with syndrome-specific therapies such as calming wind and stopping convulsions, clearing heat, eliminating dampness and resolving phlegm, and promoting diuresis and reducing swelling.
Drugs, Chinese Herbal/therapeutic use*
;
Data Mining
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Humans
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Hypertension/complications*
;
Hypertrophy, Left Ventricular/physiopathology*
;
Medicine, Chinese Traditional
;
Drug Prescriptions
3.Male genital system lymphoma: Clinicopathological analysis of 80 cases.
Xiao-Die ZHOU ; Rong-Xin QI ; Bo YU ; Xuan WANG ; Qun-Li SHI ; Qiu RAO ; Wei BAO
National Journal of Andrology 2025;31(2):138-143
OBJECTIVE:
To investigate the clinicopathological features and differential diagnosis of male genital system lymphoma (MGSL).
METHODS:
We retrospectively analyzed the clinicopathological and immunophenotypic features and prognosis of 80 cases of MGSL.
RESULTS:
The onset age of the MGSL patients ranged from 4 to 85 (median 62) years old. All the cases showed non-specificity of the imaging features and clinical manifestations. MGSL was located mainly in the testis (n = 66), followed by the prostate (n = 7), epididymis (n = 3), scrotum (n = 3) and penile glans (n = 1). Diffused large B cell lymphoma (DLBCL) was the most common pathological type (n = 62), next came extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT) (n = 7) and other rare types (n = 12). During the 1-112-month follow-up of 10 of the 19 patients, 1 died at 1 month after diagnosed with prostatic B-lymphoblastic lymphoma (B-LBL) and another 1 died at 50 months after diagnosed with testicular DLBCL.
CONCLUSION
MGSL is rare clinically, mainly of the DLBCL type pathologically, lacking specificity in clinical symptoms and imaging manifestation. The definite diagnosis of the malignancy depends on histopathology combined with related molecular examination and immunohistochemical labeling, and R-CHOP chemotherapy is the first choice for its treatment.
Humans
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Male
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Middle Aged
;
Aged
;
Retrospective Studies
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Adult
;
Aged, 80 and over
;
Young Adult
;
Adolescent
;
Child
;
Child, Preschool
;
Genital Neoplasms, Male/diagnosis*
;
Prognosis
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Lymphoma, Large B-Cell, Diffuse/diagnosis*
;
Lymphoma/diagnosis*
4.Electroacupuncture alleviates behaviors associated with posttraumatic stress disorder by modulating lipocalin-2-mediated neuroinflammation and neuronal activity in the prefrontal cortex.
Yu-Die YANG ; Wen ZHONG ; Ming CHEN ; Qing-Chen TANG ; Yan LI ; Lu-Lu YAO ; Mei-Qi ZHOU ; Neng-Gui XU ; Shuai CUI
Journal of Integrative Medicine 2025;23(5):537-547
OBJECTIVE:
To elucidate the specific mechanisms by which electroacupuncture (EA) alleviates anxiety and fear behaviors associated with posttraumatic stress disorder (PTSD), focusing on the role of lipocalin-2 (Lcn2).
METHODS:
The PTSD mouse model was subjected to single prolonged stress and shock (SPS&S), and the animals received 15 min sessions of EA at Shenmen acupoint (HT7). Behavioral tests were used to investigate the effects of EA at HT7 on anxiety and fear. Western blotting and enzyme-linked immunosorbent assay were used to quantify Lcn2 and inflammatory cytokine levels in the prefrontal cortex (PFC). Additionally, the activity of PFC neurons was evaluated by immunofluorescence and in vivo electrophysiology.
RESULTS:
Mice subjected to SPS&S presented increased anxiety- and fear-like behaviors. Lcn2 expression in the PFC was significantly upregulated following SPS&S, leading to increased expression of the proinflammatory cytokines tumor necrosis factor-α and interleukin-6 and suppression of PFC neuronal activity. However, EA at HT7 inhibited Lcn2 release, reducing neuroinflammation and hypoexcitability in the PFC. Lcn2 overexpression mitigated the effects of EA at HT7, resulting in anxiety- and fear-like behaviors.
CONCLUSION
EA at HT7 can ameliorate PTSD-associated anxiety and fear, and its mechanism of action appears to involve the inhibition of Lcn2-mediated neural activity and inflammation in the PFC. Please cite this article as: Yang YD, Zhong W, Chen M, Tang QC, Li Y, Yao LL, et al. Electroacupuncture alleviates behaviors associated with posttraumatic stress disorder by modulating lipocalin-2-mediated neuroinflammation and neuronal activity in the prefrontal cortex. J Integr Med. 2025; 23(5):537-547.
Electroacupuncture
;
Stress Disorders, Post-Traumatic/metabolism*
;
Animals
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Lipocalin-2/metabolism*
;
Prefrontal Cortex/physiopathology*
;
Male
;
Mice
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Neurons/physiology*
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Disease Models, Animal
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Fear
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Behavior, Animal
;
Mice, Inbred C57BL
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Neuroinflammatory Diseases/metabolism*
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Anxiety/therapy*
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Acupuncture Points
5.Self-screening for arteriosclerosis in middle-aged and elderly residents and the construction of a primary care initial screening tool
Yue MENG ; Li ZHENG ; Jing ZHOU ; Dashan WANG ; Jin HU ; Die WANG ; You LI ; Junhua WANG ; Ziyun WANG
The Journal of Practical Medicine 2024;40(14):1947-1951
Objective To establish a simple model for arteriosclerosis(AS)screening to provide a viable tool for the timely identification of AS risk among residents aged 40~65 years.Methods Data were obtained from the Sleep and Chronic Diseases Program in Fuquan City.The original dataset was divided into a training subset and a validation subset(80%:20%).LASSO and logistic regression models were used to screen variables,perform multivariate regression analyses.Internal validation was performed using the Bootstrap method.Nomogram Plot was constructed,and risk score thresholds were determined based on ROC curves to classify high-risk populations.Results RS Model was established to include age,gender,napping,sleep efficiency,sleep disorders,hyperten-sion and diabetes,with AUC=74.80%and a model risk score threshold=84.20.PHC Model was established to include age,gender,napping,sleep efficiency,systolic blood pressure,fasting blood glucose,and pulse variables,with AUC=82.80%and a risk score threshold of 78.00.Decision curves showed that both models performed well in terms of calibration and actual benefits for health management.Conclusion The two AS screening models exhibit acceptable accuracy and differentiation.Therefore,it can be applied in residents'self-health management and in primary care organizations'screening work in a large scale.
6.Analysis of the impact of emergency treatment channel on the curative effect of patients with upper gastrointestinal bleeding based on the inverse probability of treatment weighting
Weifeng GOU ; Xiaoqian ZHOU ; Die DENG ; Jingbin JIANG
Chinese Journal of Integrated Traditional and Western Medicine in Intensive and Critical Care 2024;31(2):203-207
Objective To explore the clinical effectiveness of emergency upper gastrointestinal bleeding channel for patients with acute upper gastrointestinal bleeding(AUGIB)by the inverse probability of treatment weighted(IPTW)method.Methods A retrospective study method was used.The clinical information was collected on 299 AUGIB patients who belonged to the First People's Hospital of Guiyang,where they were admitted from January 2018 to December 2021.AUGIB patients admitted before the establishment of emergency treatment channel(from January 2018 to December 2019)were selected as the routinel group(152 cases),while AUGIB patients admitted after the establishment of emergency treatment channel(from January 2020 to December 2021)were selected as the channel group(147 cases).IPTW was used to balance multiple confounding variables[gender,age,history of previous underlying diseases,history of non-steroidal anti-inflammatory drug(NSAID)administration,personal history,Glasgow-Blatchford score(GBS),different bleeding etiologies,etc.],a consistent distribution of confounding variables among the groups was achieved after IPTW treatment.The difference of clinical treatment effects between the routine group and the channel group was performed,including time to hemostasis,recurrent bleeding rate,volume of blood transfusions,length of hospital stay,hospitalization cost,intensive care unit(ICU)transfer rate,and mortality etc.were compared.Results After IPTW,the confounding variables were well-balanced between groups.The time to hemostasis[hours:7.90(5.36,11.42)vs.9.92(6.25,18.15)],recurrent bleeding rate[23.1%(34/147)vs.40.1%(61/152)],length of hospital stay[days:8.00(7.00,10.34)vs.9.00(7.00,13.00)],ICU transfer rate[8.8%(13/147)vs.17.7%(27/152)],and mortality[0.7%(1/147)vs.4.5%(7/152)]in channel group were significantly lower than those in the routine group(all P<0.05).There were no significant difference in transfusions volume and hospital cost between channel group and routine group[transfusions volume(U):2(0,4)vs.2(0,4),hospitalization cost(ten thousand yuan):1.35(1.03,2.00)vs.1.16(0.71,2.29),both P>0.05].Conclusion The emergency treatment channel can reduce the recurrent bleeding rate,ICU transfer rate,and mortality rate,shorten the time of hemostasis and length of hospital stay,and has a good treatment effect.
7.Association between body health score and the risk of hypertension among health examination population aged 40-65 years
Dashan WANG ; Li ZHENG ; Jing ZHOU ; Jin HU ; Yue MENG ; You LI ; Die WANG ; Junhua WANG ; Ziyun WANG
Chinese Journal of Health Management 2024;18(8):581-586
Objective:To analyze the association between body health score and the risk of hypertension among health examination population aged 40-65 years.Methods:This study was a cross-sectional study, and 1 104 people aged 40-65 years who underwent physical examination at the Physical Examination Centre of the First People′s Hospital of Fuquan City from March to November 2022 were selected. Clinical data, such as general information, physical examination, body composition and history of hypertension diseases, were collected. The body health score was reported by the Xiaomi Body Fat Scale′s accompanying exercise health software, and was calculated by combining body fat, water and other body composition data. The association between body health score and the risk of hypertension was analyzed using restricted cubic spline regression models, while a sensitivity analysis and sex-stratified analyses were performed. Multivariate logistic regression combined with stratified analysis was used to explore the association between dimensions of body composition and the risk of hypertension.Results:The body health score was significantly lower in hypertensive patients than in non-hypertensive patients among the 1 104 health examination population [52.0(30.0) vs 69.0(35.8) points] ( Z=-8.547, P<0.001). The lower the body health score, the higher the risk of hypertension ( χ2=18.48, PNonlinear<0.001). In the total population, high body mass index was associated with an increased risk of hypertension ( OR=1.744, 95% CI: 1.104-2.765), high protein content was associated with a reduced risk of hypertension ( OR=0.587, 95% CI: 0.344-0.982) (both P<0.05). Gender-stratified analyses showed that high protein content was associated with a reduced risk of hypertension only in men ( OR=0.233, 95% CI: 0.080-0.592) ( P=0.004). High body mass index was positively associated with the risk of hypertension when the body health score was ≥60 points ( OR=2.378, 95% CI: 1.255-4.542) ( P=0.008). High visceral adiposity index (VAI) was positively associated with the risk of hypertension when the body health score was <60 points ( OR=4.395, 95% CI: 1.466-13.620), and high protein content was negatively associated with the risk of hypertension ( OR=0.255, 95% CI: 0.091-0.638) (all P<0.05). Conclusions:Health examination population aged 40-65 years with lower scores of physical health are more likely to have a risk of hypertension. Men should pay attention to the impact of body protein in hypertension risk prevention and control. The effect of body mass index should be noted when body health scores are ≥60 points, and the effect of VAI and body protein should be considered when body health scores are <60 points.
8.Expressions of androgen receptor and human epidermal growth factor receptor 2 in urinary bladder urothelial carcinoma with incidental prostate cancer and clinicopathological features of the malignancy.
Xiao-Die ZHOU ; Na SHI ; Jian-Jun WANG ; Xuan WANG ; Bo YU ; Qun-Li SHI ; Qiu RAO ; Wei BAO
National Journal of Andrology 2024;30(12):1081-1085
OBJECTIVE:
To investigate the clinicopathological features and prognosis of urinary bladder urothelial carcinoma (UBUC) with incidental prostate cancer (IPCa).
METHODS:
We retrospectively analyzed the clinicopathological features of 65 cases of UBUC and 38 cases of UBUC + IPCa after radical cystoprostatectomy (RCP) from January 2017 to February 2020. We compared their expressions of the immunohistochemical markers androgen receptor (AR) and (human epidermal growth factor receptor 2,HER2) between the two groups of patients, and analyzed their clinicopathological characteristics by chi-square test and their survival rates using the Kaplan-Meier method and log-rank test.
RESULTS:
The detection rate of UBUC + IPCa was 16.5%, and that of clinically significant IPCa was 39.5%, with preoperative PSA≥4 μg/L in 23.7% of the patients. Compared with the patients with UBUC, most of the UBUC + IPCa cases had no smoking history (73.8% vs 92.1%, P = 0.024), and fewer had histological variants (43.1% vs 10.5%, P = 0.003). The incidence rate of vascular invasion was significantly higher in the UBUC than in the UBUC + IPCa group (49.2% vs 21.1%, P = 0.005), and so was the rate of advanced cases (67.7% vs 31.6%, P<0.001). In comparison with the patients of the UBUC group, those of the UBUC + IPCa group showed remarkably higher expressions of AR (9.2% vs 31.6%, P = 0.004) and HER2 (43.1% vs 71.1%, P = 0.006). The mean overall survival time was longer in the UBUC + IPCa than in the UBUC group (48.8 mo [95% CI: 2.5-42.6 mo] vs 39.9 mo [95% CI: 2.8-34.5 mo]), but with no statistically significant difference between the two groups (P = 0.608).
CONCLUSION
Standardized sampling of prostate samples after RCP helps to improve the detection rate of IPCa. Preoperative level of PSA is not a good predictor of IPCa. Few patients with UBUC + IPCa have a history of cigarette smoking, and the predominant histological type of the malignancy is high-grade invasive urothelial carcinoma, which is not significantly different from UBUC in prognosis. The expressions of HER2 and AR are significantly higher in UBUC + IPCa than in UBUC, suggesting that UBUC + IPCa may benefit from HER2- and AR-targeted therapy.
Humans
;
Male
;
Urinary Bladder Neoplasms/metabolism*
;
Receptors, Androgen/metabolism*
;
Prostatic Neoplasms/metabolism*
;
Retrospective Studies
;
Receptor, ErbB-2/metabolism*
;
Prognosis
;
Middle Aged
;
Aged
;
Survival Rate
;
Prostatectomy
9.Diagnosis status and genetic characteristics analysis of Fanconi anemia in China.
Niu LI ; Die Xin HU ; Xia QIN ; Yi Ping ZHU ; Ming ZHOU ; Lan HE ; Li Xian CHANG ; Xiao Jun XU ; Yan DAI ; Xing Yu CAO ; Kai CHEN ; Hong Mei WANG ; Chun Jing WANG ; Yue Lin HE ; Xiao Wen QIAN ; Lan Ping XU ; Jing CHEN
Chinese Journal of Pediatrics 2023;61(10):889-895
Objective: To analyze the clinical and molecular diagnostic status of Fanconi anemia (FA) in China. Methods: The General situation, clinical manifestations and chromosome breakage test and genetic test results of 107 pediatric FA cases registered in the Chinese Blood and Marrow Transplantation Registry Group (CBMTRG) and the Chinese Children Blood and Marrow Transplantation Registry Group (CCBMTRG) from August 2009 to January 2022 were analyzed retrospectively. Children with FANCA gene variants were divided into mild and severe groups based on the type of variant, and Wilcoxon-test was used to compare the phenotypic differences between groups. Results: Of the 176 registered FA patients, 69 (39.2%) cases were excluded due to lack of definitive genetic diagnosis results, and the remaining 107 children from 15 hospitals were included in the study, including 70 males and 37 females. The age at transplantation treatment were 6 (4, 9) years. The enrolled children were involved in 10 pathogenic genes, including 89 cases of FANCA gene, 7 cases of FANCG gene, 3 cases of FANCB gene, 2 cases of FANCE gene and 1 case each of FANCC, FANCD1, FANCD2, FANCF, FANCJ, and FANCN gene. Compound heterozygous or homozygous of loss-of-function variants account for 69.2% (72/104). Loss-of-function variants account for 79.2% (141/178) in FANCA gene variants, and 20.8% (37/178) were large exon deletions. Fifty-five children (51.4%) had chromosome breakage test records, with a positive rate of 81.8% (45/55). There were 172 congenital malformations in 80 children.Café-au-Lait spots (16.3%, 28/172), thumb deformities (16.3%,28/172), polydactyly (13.9%, 24/172), and short stature (12.2%, 21/172) were the most common congenital malformations in Chinese children with FA. No significant difference was found in the number of congenital malformations between children with severe (50 cases) and mild FANCA variants (26 cases) (Z=-1.33, P=0.185). Conclusions: FANCA gene is the main pathogenic gene in children with FA, where the detection of its exon deletion should be strengthened clinically. There were no phenotypic differences among children with different types of FANCA variants. Chromosome break test is helpful to determine the pathogenicity of variants, but its accuracy needs to be improved.
Male
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Female
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Humans
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Child
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Fanconi Anemia/genetics*
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Chromosome Breakage
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Retrospective Studies
;
Exons
;
China/epidemiology*

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