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.Correlation between posterior longitudinal ligament injury and vertebral body injury parameters in thoracolumbar burst fractures
Qiang HE ; Xuejun YANG ; Feng LI ; Baolong YU ; Shengxiang LIU ; Xu GAO ; Zhi HUANG ; Wenkai ZHENG ; Yifeng DA ; Zhi WANG ; Wenhua XING
Chinese Journal of Orthopaedics 2024;44(22):1474-1481
Objective:To evaluate the correlation between the degree of posterior longitudinal ligament (PLL) injury and various parameters of vertebral body injury in patients with thoracolumbar burst fractures.Methods:A total of 48 patients with thoracolumbar burst fractures were admitted to the Spine Surgery Center of the Second Affiliated Hospital of Inner Mongolia Medical University between December 2022 and January 2024. The cohort consisted of 31 males and 17 females, with a mean age of 44.1±11.8 years (range, 18-65 years). Based on the PLL injury grading method proposed by Sun Zhaoyun, patients were classified into three groups: mild, moderate, and severe. However, due to an insufficient number of patients in the severe group ( n=3), the moderate and severe groups were combined for statistical analysis, resulting in two groups: mild, and moderate-to-severe. Patient demographic and clinical data were collected. Local kyphosis (LK), inversion angle (IA), horizontal rotation angle (HRA), increased interspinous distance (IISD), anterior vertebral body compression ratio (AVBCR), posterior vertebral body compression ratio (PVBCR), middle vertebral body compression ratio (MVBCR), the ratio of height of bone fragment (RHBF), the ratio of width of bone fragment (RWBF), and mid-sagittal canal diameter compression ratio (MSDCR) were measured. Statistical analyses were performed using SPSS 25.0. Categorical variables were expressed as frequency (percentage) and analyzed using chi-square and Fisher exact tests. Continuous variables were tested for normality, with non-normally distributed data analyzed using the rank-sum test and expressed as median (interquartile range). Multivariate logistic regression analysis was performed to identify independent risk factors, and receiver operating characteristic (ROC) curves were plotted to calculate the area under the curve (AUC) to evaluate predictive performance. Results:Among the 48 patients, only 3 were found to have severe PLL injury, necessitating the combination of the moderate and severe groups for statistical purposes. Patients in the moderate-to-severe group demonstrated significantly higher AVBCR, PVBCR, RHBF, MVBCR, MSDCR, and IA compared to the mild group ( P<0.05). Multivariate logistic regression identified AVBCR, PVBCR, MSDCR, and IA as independent risk factors for moderate-to-severe PLL injury ( OR>1, P<0.05). ROC curve analysis revealed that AVBCR, PVBCR, MSDCR, IA, and their combined index could effectively predict moderate-to-severe PLL injury ( P<0.05). Notably, the combined index showed superior predictive performance (AUC=0.970) compared to individual parameters. Threshold values were determined as follows: AVBCR>45.30%, PVBCR>12.17%, MSDCR>27.13%, IA>5.90°, and the combined index >0.61, indicating PLL damage. Conclusion:AVBCR, PVBCR, MSDCR, IA, and their combined index are significantly associated with moderate-to-severe PLL injury in thoracolumbar burst fractures. The combined index demonstrates superior predictive ability compared to single parameters, providing a reliable tool for assessing PLL integrity.
3.Identification of a novel splice site mutation in the DNAAF4 gene of a Chinese patient with primary ciliary dyskinesia.
Yang XU ; Jing WANG ; Ji-Hai LIU ; Qing-Qiang GAO ; Bing WANG ; Zhi-Peng XU
Asian Journal of Andrology 2023;25(6):713-718
Primary ciliary dyskinesia (PCD) is a rare hereditary orphan condition that results in variable phenotypes, including infertility. About 50 gene variants are reported in the scientific literature to cause PCD, and among them, dynein axonemal assembly factor 4 ( DNAAF4 ) has been recently reported. DNAAF4 has been implicated in the preassembly of a multiunit dynein protein essential for the normal function of locomotory cilia as well as flagella. In the current study, a single patient belonging to a Chinese family was recruited, having been diagnosed with PCD and asthenoteratozoospermia. The affected individual was a 32-year-old male from a nonconsanguineous family. He also had abnormal spine structure and spinal cord bends at angles diagnosed with scoliosis. Medical reports, laboratory results, and imaging data were investigated. Whole-exome sequencing, Sanger sequencing, immunofluorescence analysis, hematoxylin-eosin staining, and in silico functional analysis, including protein modeling and docking studies, were used. The results identified DNAAF4 disease-related variants and confirmed their pathogenicity. Genetic analysis through whole-exome sequencing identified two pathogenic biallelic variants in the affected individual. The identified variants were a hemizygous splice site c.784-1G>A and heterozygous 20.1 Kb deletion at the DNAAF4 locus, resulting in a truncated and functionless DNAAF4 protein. Immunofluorescence analysis indicated that the inner dynein arm was not present in the sperm flagellum, and sperm morphological analysis revealed small sperm with twisted and curved flagella or lacking flagella. The current study found novel biallelic variants causing PCD and asthenoteratozoospermia, extending the range of DNAAF4 pathogenic variants in PCD and associated with the etiology of asthenoteratozoospermia. These findings will improve our understanding of the etiology of PCD.
Adult
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Humans
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Male
;
Asthenozoospermia/genetics*
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Dyneins/genetics*
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East Asian People
;
Kartagener Syndrome/genetics*
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Mutation
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Proteins/genetics*
;
Semen/metabolism*
4.Concomitant occurrences of pulmonary embolism and acute myocardial infarction in acute coronary syndrome patient undergoing percutaneous coronary intervention: a case report.
Zhi-Qiang YANG ; Shu-Tong DONG ; Qiao-Yu SHAO ; Yu-Fei WANG ; Qiu-Xuan LI ; Zai-Qiang LIU ; Xiao-Teng MA ; Jing LIANG ; Dong-Mei SHI ; Yu-Jie ZHOU ; Fei GAO ; Zhi-Jian WANG
Journal of Geriatric Cardiology 2023;20(12):880-885
5. Finite element analysis of 14-year-old adolescent after spinal foraminoplasty at L
Ming-Jie GAO ; Li-Na DAI ; Li-Rong SHA ; Zhi-Qiang WANG ; Xiao-He LI ; Hai-Yan WANG ; Yang-Yang XU ; Yun-Feng ZHANG ; Feng JIN ; Kai ZHANG
Acta Anatomica Sinica 2023;54(3):335-341
Objective To establish the three-dimensional finite element model of lumbar spine(L) 3-5 segments of the normal spine of 14-year-old adolescents to analyze the biomechanical changes of the lumbar spine after different degrees of lumbar foraminal plasty, and to provide reference for improvement of adolescent foraminoplasty. Methods A14-year-old female volunteer with no previous history of lumbar spine was selected to collect lumbar CT image data and we imported it into Mimics 16.0 software for modeling. ABAQUS software was used to conduct finite element model force analysis. Models M
7.A case of low-grade fibromyxoid sarcoma of the temporal bone.
Ming Yang MAO ; Guo Dong FENG ; Yu CHEN ; Xiao Hua SHI ; Xu TIAN ; Tong SU ; Hui Ying SUN ; Zhen Tan XU ; Wen Sheng REN ; Zhu Hua ZHANG ; Zhi Qiang GAO ; Zheng Yu JIN
Chinese Journal of Otorhinolaryngology Head and Neck Surgery 2023;58(1):64-67
8.Exploration and Practice of the "One Combination, Two Highlights, Three Combinations, Four in One" Innovative Talents Training Mode in Forensic Medicine.
Jiang-Wei YAN ; Jun-Hong SUN ; Hong-Xing WANG ; Zhi-Wen WEI ; Xiang-Jie GUO ; Ji LI ; Cai-Rong GAO ; Geng-Qian ZHANG ; Xin-Hua LIANG ; Qiang-Qiang ZHANG ; Hong-Wei WANG ; Si-Jin LI ; Ying-Yuan WANG ; Ke-Ming YUN
Journal of Forensic Medicine 2023;39(2):193-199
Talent is one of the basic and strategic supports for building a modern socialist country in all aspects. Since the 1980s, the establishment of forensic medicine major and the cultivation of innovative talents in forensic medicine have become hot topics in higher education in forensic medicine. Over the past 43 years, the forensic medicine team of Shanxi Medical University has adhered to the joint education of public security and colleges, and made collaborative innovation, forming a training mode of "One Combination, Two Highlights, Three Combinations, Four in One" for innovative talents in forensic medicine. It has carried out "5+3/X" integrated reform, and formed a relatively complete talent training innovation mode and management system in teaching, scientific research, identification, major, discipline, team, platform and cultural construction. It has made a historic contribution to China's higher forensic education, accumulated valuable experience for the construction of first-class major and first-class discipline of forensic medicine, and provided strong support for the construction of the national new forensic talent training system. The popularization of this training mode is conducive to the rapid and sustainable development of forensic science, and provides more excellent forensic talents for national building, regional social development and the discipline construction of forensic science.
Humans
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Forensic Medicine/education*
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Aptitude
9.Molecular features of 109 patients with chronic myelomonocytic leukemia in a single center.
Shi Qiang QU ; Li Juan PAN ; Tie Jun QIN ; Ze engF XU ; Bing LI ; Hui Jun WANG ; Qi SUN ; Yu Jiao JIA ; Cheng Wen LI ; Wen Yun CAI ; Qing Yan GAO ; Meng JIAO ; Zhi Jian XIAO
Chinese Journal of Hematology 2023;44(5):373-379
Objective: To explore the molecular features of chronic myelomonocytic leukemia (CMML) . Methods: According to 2022 World Health Organization (WHO 2022) classification, 113 CMML patients and 840 myelodysplastic syndrome (MDS) patients from March 2016 to October 2021 were reclassified, and the clinical and molecular features of CMML patients were analyzed. Results: Among 113 CMML patients, 23 (20.4%) were re-diagnosed as acute myeloid leukemia (AML), including 18 AML with NPM1 mutation, 3 AML with KMT2A rearrangement, and 2 AML with MECOM rearrangement. The remaining 90 patients met the WHO 2022 CMML criteria. In addition, 19 of 840 (2.3%) MDS patients met the WHO 2022 CMML criteria. At least one gene mutation was detected in 99% of CMML patients, and the median number of mutations was 4. The genes with mutation frequency ≥ 10% were: ASXL1 (48%), NRAS (34%), RUNX1 (33%), TET2 (28%), U2AF1 (23%), SRSF2 (21.1%), SETBP1 (20%), KRAS (17%), CBL (15.6%) and DNMT3A (11%). Paired analysis showed that SRSF2 was frequently co-mutated with ASXL1 (OR=4.129, 95% CI 1.481-11.510, Q=0.007) and TET2 (OR=5.276, 95% CI 1.979-14.065, Q=0.001). SRSF2 and TET2 frequently occurred in elderly (≥60 years) patients with myeloproliferative CMML (MP-CMML). U2AF1 mutations were often mutually exclusive with TET2 (OR=0.174, 95% CI 0.038-0.791, Q=0.024), and were common in younger (<60 years) patients with myelodysplastic CMML (MD-CMML). Compared with patients with absolute monocyte count (AMoC) ≥1×10(9)/L and <1×10(9)/L, the former had a higher median age of onset (60 years old vs 47 years old, P<0.001), white blood cell count (15.9×10(9)/L vs 4.4×10(9)/L, P<0.001), proportion of monocytes (21.5% vs 15%, P=0.001), and hemoglobin level (86 g/L vs 74 g/L, P=0.014). TET2 mutations (P=0.021) and SRSF2 mutations (P=0.011) were more common in patients with AMoC≥1×10(9)/L, whereas U2AF1 mutations (P<0.001) were more common in patients with AMoC<1×10(9)/L. There was no significant difference in the frequency of other gene mutations between the two groups. Conclusion: According to WHO 2022 classification, nearly 20% of CMML patients had AMoC<1×10(9)/L at the time of diagnosis, and MD-CMML and MP-CMML had different molecular features.
Humans
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Aged
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Middle Aged
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Leukemia, Myelomonocytic, Chronic/genetics*
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Prognosis
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Splicing Factor U2AF/genetics*
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Mutation
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Myelodysplastic Syndromes/genetics*
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Leukemia, Myeloid, Acute/genetics*
10.Da Chengqitang in Treatment of Sepsis: A Review
Junsheng SHA ; Nan ZHANG ; Weiyi SUN ; Xiang LI ; Shifa YANG ; Qiang ZHI ; Shu CHEN ; Nan GAO ; Liyan FAN
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(17):274-282
Sepsis is a systemic inflammatory syndrome induced by infection and other factors, with the number of patients worldwide exceeding 10 million each year. The pathophysiological mechanism is of this disease complex. Sepsis is often accompanied by endotoxin translocation, gastrointestinal dysfunction, inflammatory cytokine activation, immune dysregulation, coagulation disorder, multiple organ function impairment and many other body imbalances, as well as systemic inflammation, apoptosis, oxidative stress injury and other cell damage mechanisms. This disease causes a heavy medical burden due to the difficult diagnosis and treatment and the poor prognosis. Great progress has been achieved in the diagnosis and treatment of sepsis with traditional Chinese medicine (TCM) and western medicine. The value of western medicine in the diagnosis and treatment of sepsis is limited due to antibiotic resistance, hormone abuse, and high medical costs. Sepsis is classified as a warm disease or typhoid fever in TCM. Da Chengqitang is a classical formula in the Treatise on Typhoid Fever to deal with the excess syndrome of Yang brightness Fu-organ. Modern medicine has proved that Da Chengqitang has the effect of inhibiting oxidative stress, reducing inflammation, and delaying apoptosis by improving gastrointestinal dynamics and regulating intestinal microecology. On the basis of the previous theoretical basis and the rich experience in the medication, medical practitioners have proposed a new therapeutic concept of using Da Chengqitang in combination with western drugs from a holistic view involving both bacteria and toxicity for treating both the symptoms and the root cause, which has a wide range of application. The article reviews the classical research and latest findings of Da Chengqitang in the treatment of sepsis, with a view to clarifying the mechanism and advantages of this formula in the adjuvant treatment of sepsis, exploring its potential efficacy, and providing timely, adequate, and scientific theoretical support for the promotion of this formula in the clinical practice.

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