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.Differences in growth and secondary metabolite accumulation of Panax quinquefolius between understory and field planting in Shandong, China.
Yue WANG ; Xin-Ying MAO ; Yu DING ; Hong-Xia YU ; Zhi-Fang RAN ; Xiao-Li CHEN ; Jie ZHOU
China Journal of Chinese Materia Medica 2025;50(6):1524-1533
In order to compare the differences in growth and secondary metabolite accumulation of Panax quinquefolius between understory and field planting, growth indexes, photosynthetic characteristics, soil enzyme activities, secondary metabolite contents, and antioxidant activities of P. quinquefolius under different planting modes were examined and compared, and One-way analysis of variance(ANOVA) and correlation analyses were carried out by using the software SPSS 25.0 and GraphPad Prism 9.5. The Origin 2021 software was used for plotting. The results showed that compared with those under field planting, the plant height, leaf length, leaf width, photosynthetic rate, and chlorophyll content of P. quinquefolius under understory planting were significantly reduced, and arbuscular mycorrhizal fungi(AMF) infestation rate and infestation intensity, ginsenoside content, and antioxidant activity were significantly increased. The activities of inter-root soil urease, sucrase, and catalase increased, while the activities of non-inter-root soil urease and alkaline phosphatase increased. Correlation analyses showed that the plant height and leaf length of P. quinquefolius plant were significantly positively correlated with net photosynthetic rate, transpiration rate, chlorophyll content, and electron transfer rate(P<0.05), while ginsenoside content was significantly negatively correlated with net photosynthetic rate, chlorophyll content, and electron transfer rate(P<0.05) and significantly positively correlated with AMF infestation rate and infestation intensity(P<0.05). In addition, ginsenoside content was significantly positively correlated with the activities of inter-root soil sucrase, urease, and catalase(P<0.05). This study provides basic data for revealing the mechanism of secondary metabolite accumulation in P. quinquefolius under understory planting and for exploring and practicing the ecological mode of P. quinquefolius under understory planting.
Panax/microbiology*
;
China
;
Secondary Metabolism
;
Soil/chemistry*
;
Photosynthesis
;
Plant Leaves/metabolism*
;
Chlorophyll/metabolism*
;
Mycorrhizae
3.Clinical Features, Prognostic Analysis and Predictive Model Construction of Central Nervous System Invasion in Peripheral T-Cell Lymphoma.
Ya-Ting MA ; Yan-Fang CHEN ; Zhi-Yuan ZHOU ; Lei ZHANG ; Xin LI ; Xin-Hua WANG ; Xiao-Rui FU ; Zhen-Chang SUN ; Yu CHANG ; Fei-Fei NAN ; Ling LI ; Ming-Zhi ZHANG
Journal of Experimental Hematology 2025;33(3):760-768
OBJECTIVE:
To investigate the clinical features and prognosis of central nervous system (CNS) invasion in peripheral T-cell lymphoma (PTCL) and construct a risk prediction model for CNS invasion.
METHODS:
Clinical data of 395 patients with PTCL diagnosed and treated in the First Affiliated Hospital of Zhengzhou University from 1st January 2013 to 31st December 2022 were analyzed retrospectively.
RESULTS:
The median follow-up time of 395 PTCL patients was 24(1-143) months. There were 13 patients diagnosed CNS invasion, and the incidence was 3.3%. The risk of CNS invasion varied according to pathological subtype. The incidence of CNS invasion in patients with anaplastic large cell lymphoma (ALCL) was significantly higher than in patients with angioimmunoblastic T-cell lymphoma (AITL) (P <0.05). The median overall survival was significantly shorter in patients with CNS invasion than in those without CNS involvement, with a median survival time of 2.4(0.6-127) months after diagnosis of CNS invasion. The results of univariate and multivariate analysis showed that more than 1 extranodal involvement (HR=4.486, 95%CI : 1.166-17.264, P =0.029), ALCL subtype (HR=9.022, 95%CI : 2.289-35.557, P =0.002) and ECOG PS >1 (HR=15.890, 95%CI : 4.409-57.262, P <0.001) were independent risk factors for CNS invasion in PTCL patients. Each of these risk factors was assigned a value of 1 point and a new prediction model was constructed. It could stratify the patients into three distinct groups: low-risk group (0-1 point), intermediate-risk group (2 points) and high-risk group (3 points). The 1-year cumulative incidence of CNS invasion in the high-risk group was as high as 50.0%. Further evaluation of the model showed good discrimination and accuracy, and the consistency index was 0.913 (95%CI : 0.843-0.984).
CONCLUSION
The new model shows a precise risk assessment for CNS invasion prediction, while its specificity and sensitivity need further data validation.
Humans
;
Lymphoma, T-Cell, Peripheral/pathology*
;
Prognosis
;
Retrospective Studies
;
Central Nervous System Neoplasms/pathology*
;
Neoplasm Invasiveness
;
Male
;
Female
;
Central Nervous System/pathology*
;
Middle Aged
;
Adult
4.Prognostic Significance of Endothelial Activation and Stress Index in Mantle Cell Lymphoma.
Xin-Yue ZHOU ; Zhi-Qin YANG ; Jin HU ; Feng-Yi LU ; Qian-Nan HAN ; Huan-Huan ZHAO ; Wen-Xia GAO ; Yu-Han MA ; Hu-Jun LI ; Zhen-Yu LI ; Kai-Lin XU ; Wei CHEN
Journal of Experimental Hematology 2025;33(4):1051-1056
OBJECTIVE:
To investigate the predictive value of endothelial activation and stress index (EASIX) for the prognosis of patients with mantle cell lymphoma (MCL).
METHODS:
A retrospective analysis was conducted to assess prognosis and compare the clinical features of patients diagnosed with MCL who were admitted to the Affiliated Hospital of Xuzhou Medical University from January 2010 to June 2023, had therapeutic indications and received standard treatment.
RESULTS:
A total of 66 patients were included and divided into high EASIX group and low EASIX group, according to a cutoff value of 0.97 determined by the receiver operating characteristic (ROC) curve. Multivariate Cox regression analysis showed that prealbumin <0.2 g/L, high EASIX, and ECOG PS score ≥2 were independent risk factors influencing overall survival (OS) in MCL patients. The median OS of patients in the high and low EASIX group was 13.0 and 37.5 months, and the median progression-free survival was 8.8 and 26.0 months, respectively. The proportions of patients with ECOG PS score ≥2 and prealbumin <0.2 g/L at onset significantly increased in the high EASIX group compared to those in the low EASIX group.
CONCLUSION
At the time of initial diagnosis, EASIX can serve as an independent prognostic indicator impacting OS in patients with MCL. Furthermore, patients in the high EASIX group experience a poorer prognosis and shorter survival duration compared with those in the low EASIX group.
Humans
;
Lymphoma, Mantle-Cell/pathology*
;
Prognosis
;
Retrospective Studies
;
Male
;
Female
;
Middle Aged
;
Aged
;
ROC Curve
5.The Role of the Modified Endothelial Activation and Stress Index (mEASIX) in Predicting the Efficacy of CAR-T Cell Therapy and Cytokine Release Syndrome (CRS).
Jin HU ; Qian-Nan HAN ; Feng-Yi LU ; Xin-Yue ZHOU ; Zhi-Qin YANG ; Kai-Lin XU ; Wei CHEN
Journal of Experimental Hematology 2025;33(4):1190-1198
OBJECTIVE:
To investigate the predictive role of the modified Endothelial Activation and Stress Index (mEASIX) in the efficacy of chimeric antigen receptor T-cell (CAR-T) therapy and cytokine release syndrome (CRS).
METHODS:
The clinical data of 70 relapsed and refractory (R/R) B-cell tumor patients who were treated with CAR-T therapy from September 1, 2018 to February 28, 2023 in the Department of Hematology, Affiliated Hospital of Xuzhou Medical University, were retrospectively analyzed. The value of log-2 mEASIX before conditioning (-7 d) was calculated, and the patients were divided into a low-mEASIX group (42 patients) and a high-mEASIX group (28 patients) based on the cut-off value of 5.443 determined by the receiver operating characteristic (ROC) curve. Eventually, the predictive role of mEASIX before conditioning on the efficacy of CAR-T cell therapy and CRS was analyzed.
RESULTS:
The high-mEASIX group exhibited significantly worse median overall survival (OS) and median progression-free survival (PFS) in comparison to the low mEASIX group (OS: 3.2 months vs not reached, P < 0.01; PFS: 1.3 months vs 6.0 months, P =0.009). The incidence of grade ≥2 CRS in the high-mEASIX group was substantially higher than that in the low-mEASIX group (57.1% vs 19.0%, P =0.007). The degree of remission after CAR-T therapy (P =0.001), whether CRS occurs or not (P =0.041), the lactate dehydrogenase (LDH) level before conditioning (P =0.046), and the mEASIX score before conditioning (P =0.047) were independent influencing factors for the OS of patients receiving CAR-T cell therapy.
CONCLUSION
The mEASIX score before conditioning can predict OS and the incidence of grade ≥2 CRS in patients with relapsed and refractory B-cell tumors who receive CAR-T cell therapy.
Cytokine Release Syndrome/therapy*
;
Immunotherapy, Adoptive/methods*
;
Humans
;
Lymphoma, B-Cell/therapy*
;
Retrospective Studies
;
Hematology
;
China
;
Receptors, Chimeric Antigen/blood*
;
Predictive Value of Tests
6.Clinical efficacy of endocrinotherapy combined with Shenqi Pills on patients with hormone-sensitive prostate cancer.
Yu-Hong XIE ; Gang YI ; Xiao-Wen YI ; Tong-Lin SUN ; Qun-Fang LIN ; Jun ZHOU ; Xin-Jun LUO ; Fang-Zhi FU ; Biao WANG ; Qin-Zheng WANG ; Lie ZHANG ; Yang YANG ; Rui-Song GAO ; Qing ZHOU
National Journal of Andrology 2025;31(4):341-348
OBJECTIVE:
The aim of this study is to explore the clinical efficacy and safety of endocrinotherapy combined with Shenqi Pills on hormone-sensitive prostate cancer (HSPC).
METHODS:
Eighty patients who were diagnosed with HSPC and renal-yang deficiency at the First Affiliated Hospital of Hunan University of Traditional Chinese Medicine and the Hospital of Traditional Chinese Medicine of Mayang Miao Autonomous County from 1st April 2021 to 30th April 2024 were randomly divided into 2 groups. The patients in the control group were treated with androgen deprivation therapy (ADT). And the patients in treatment group were treated with Shenqi Pills orally on the basis of the control group. The baseline data of the two groups were analyzed. After 36 months of treatment, the differences between the two groups were compared in terms of overall survival (OS), prostate-specific antigen (PSA) level, PSA response rate, Functional Assessment Scale for Prostate Cancer Therapy (FACT-P), Chinese medicine evidence scores, testosterone level and safety.
RESULTS:
A total of 80 study subjects were included in this study, including 42 cases in the treatment group and 38 cases in the control group. There was no statistical difference in the baseline data between the two groups before treatment (P>0.05). At the end of the observation period, a statistically significant difference in OS was found in the treatment group compared to the control group in the subgroup of patients with a disease duration ranged of 0-6 months (P<0.05). There was no statistically significant difference in PSA levels in the treatment group at 3 months (P>0.05). And the differences in the proportion of PSA50 (98.1% vs 91.4%), PSA90 (92.9% vs 84.6%) and the proportion of decrease in PSA (56.7% vs 33.8%) in the treatment group were found compared to those in the control group after 6 months of tre atment. After 12 months of treatment, the scores of FACT-4 and renal-yang deficiency in the treatment group were (95.28±7.93) and (15.73±5.70) respectively, compared to the scores in the control group ([85.46±10.12] and [18.20±4.27] (P<0.05). However, there was no significant difference in serum testosterone ([0.60±0.24] nmol/L vs [1.09±2.10] nmol/L) between the two groups (P>0.05). After 24 months of treatment, there were significant differences in in the FACT-4 total score ([97.95±7.54] vs [80.33±8.58]), renal-yang deficiency syndrome score ([14.64±5.15] vs [24.94±8.75]) between the treatment group and the control group (P<0.05). However, there was no significant difference in serum testosterone ( [0.73±1.01] nmol/L vs [0.59±0.25] nmol/L) between the two groups (P> 0.05). Better therapeutic results were showed in the treatment group in terms of total FACT-P score, physical situation score, social and family situation score, emotional state score, functional state score, additional score and renal-yang deficiency symptom score (P<0.05). After treatment, there was no serious adverse reaction in the course of treatment, and no obvious abnormality was found in the liver and kidney function of the patients from two groups.
CONCLUSION
Endocrinotherapy combined with Shenqi Pills is safe and effective in HSPC and can reduce the risk of death in HSPC patients, and the earlier the intervention, the longer the overall survival of the patients. In addition, this treatment regimen can increase the PSA response rate, improve patients' quality of life, and reduce the renal-yang deficiency syndrome score without the risk of elevating serum testosterone levels.
Humans
;
Male
;
Drugs, Chinese Herbal/therapeutic use*
;
Prostatic Neoplasms/drug therapy*
;
Androgen Antagonists/therapeutic use*
;
Prostate-Specific Antigen/blood*
;
Aged
;
Middle Aged
;
Treatment Outcome
;
Testosterone
7.Performance assessment of computed tomographic angiography fractional flow reserve using deep learning: SMART trial summary.
Wei ZHANG ; You-Bing YIN ; Zhi-Qiang WANG ; Ying-Xin ZHAO ; Dong-Mei SHI ; Yong-He GUO ; Zhi-Ming ZHOU ; Zhi-Jian WANG ; Shi-Wei YANG ; De-An JIA ; Li-Xia YANG ; Yu-Jie ZHOU
Journal of Geriatric Cardiology 2025;22(9):793-801
BACKGROUND:
Non-invasive computed tomography angiography (CTA)-based fractional flow reserve (CT-FFR) could become a gatekeeper to invasive coronary angiography. Deep learning (DL)-based CT-FFR has shown promise when compared to invasive FFR. To evaluate the performance of a DL-based CT-FFR technique, DeepVessel FFR (DVFFR).
METHODS:
This retrospective study was designed for iScheMia Assessment based on a Retrospective, single-center Trial of CT-FFR (SMART). Patients suspected of stable coronary artery disease (CAD) and undergoing both CTA and invasive FFR examinations were consecutively selected from the Beijing Anzhen Hospital between January 1, 2016 to December 30, 2018. FFR obtained during invasive coronary angiography was used as the reference standard. DVFFR was calculated blindly using a DL-based CT-FFR approach that utilized the complete tree structure of the coronary arteries.
RESULTS:
Three hundred and thirty nine patients (60.5 ±10.0 years and 209 men) and 414 vessels with direct invasive FFR were included in the analysis. At per-vessel level, sensitivity, specificity, accuracy, positive predictive value (PPV) and negative predictive value (NPV) of DVFFR were 94.7%, 88.6%, 90.8%, 82.7%, and 96.7%, respectively. The area under the receiver operating characteristics curve (AUC) was 0.95 for DVFFR and 0.56 for CTA-based assessment with a significant difference (P < 0.0001). At patient level, sensitivity, specificity, accuracy, PPV and NPV of DVFFR were 93.8%, 88.0%, 90.3%, 83.0%, and 95.8%, respectively. The computation for DVFFR was fast with the average time of 22.5 ± 1.9 s.
CONCLUSIONS
The results demonstrate that DVFFR was able to evaluate lesion hemodynamic significance accurately and effectively with improved diagnostic performance over CTA alone. Coronary artery disease (CAD) is a critical disease in which coronary artery luminal narrowing may result in myocardial ischemia. Early and effective assessment of myocardial ischemia is essential for optimal treatment planning so as to improve the quality of life and reduce medical costs.
8.Biological characteristics of spontaneous ovarian cancer in Microtusfortis.
Junkang ZHOU ; Tianqiong HE ; Yixin WEN ; Qian LIU ; Wenling ZHI ; Lingxuan OUYANG ; Yushan QI ; Xin GAO ; Zikang ZHOU ; Zhijun ZHOU
Journal of Central South University(Medical Sciences) 2025;50(1):11-22
OBJECTIVES:
Wild-caught Microtus fortis (M. fortis) at the age of 9-15 months can develop epithelial ovarian cancers similar to human epithelial ovarian cancers under natural conditions during experimental animal breeding, but its pathological types and biological characteristics remain unclear. This study aims to analyze the biological characteristics of spontaneous ovarian cancer in M. fortis, intending to develop M. fortis as an animal model for human epithelial ovarian cancer.
METHODS:
The female M. fortis (9-15 months old) with spontaneous ovarian cancer were selected as the experimental group, and healthy M. fortis from the same litter were selected as the control group. The ovarian pathological changes of the two groups were observed by dissection. Blood routine and biochemical indicators were measured by biochemical analysis. Hematoxylin and eosin (HE) staining was performed to observe the pathological changes in the ovarian cancer tissue of M. fortis. Immunohistochemical staining was used to detect the protein expression of common ovarian cancer markers, and real-time RT-PCR was used to analyze the transcription levels of ovarian cancer-related genes.
RESULTS:
Spontaneous ovarian cancer in M. fortis mainly affects both ovaries, with tumors appearing solid or cystic. HE staining and histopathological analysis confirmed that the ovarian tumors originated from ovarian surface epithelium. Compared to the control group, the experimental group showed significantly decreased hemoglobin (P<0.01), hematocrit (P<0.05), albumin (P<0.05), and blood glucose levels (P<0.01), while lymphocyte percentage (P<0.05), monocyte percentage (P<0.05), cholesterol (P<0.01), and progesterone (P<0.01) levels were significantly increased. Expression of ovarian cancer-related genes, including ID3, CDC42, RHOA, RB1CC1, NF1, PIN1, MIB1, PDS5A, MCM7, and MLH1, was significantly downregulated (all P<0.05), while PAX8 gene expression was significantly upregulated (P<0.05). Immunohistochemical results showed that Wilms' tumor gene 1 (WT1) protein was mainly distributed throughout the cell, with significantly higher expression in ovarian cancer M. fortis. Tumor protein 53 (TP53) was expressed in both healthy and ovarian cancer M. fortis and was distributed throughout the cell. Hepatocyte nuclear factor 1 beta (HNF1B) and progesterone receptor (PR) protein were highly expressed in the ovarian tissue of healthy M. fortis but were significantly reduced in the ovarian cancer M. fortis, though both were located in the cytoplasm.
CONCLUSIONS
Spontaneous ovarian cancer in M. fortis is serous ovarian cancer. Compared to healthy M. fortis, significant differences were observed in ovarian tissue morphology, biochemical indicators, ovarian cancer-related gene expression, and protein expression, which show similarity to the biological characteristics of human serous ovarian cancer. This suggests that M. fortis could be an ideal animal model for studying human serous ovarian cancer.
Female
;
Ovarian Neoplasms/metabolism*
;
Animals
;
Carcinoma, Ovarian Epithelial
;
Disease Models, Animal
;
Humans
;
Neoplasms, Glandular and Epithelial/metabolism*
;
Ovary/pathology*
9.Expert consensus on apical microsurgery.
Hanguo WANG ; Xin XU ; Zhuan BIAN ; Jingping LIANG ; Zhi CHEN ; Benxiang HOU ; Lihong QIU ; Wenxia CHEN ; Xi WEI ; Kaijin HU ; Qintao WANG ; Zuhua WANG ; Jiyao LI ; Dingming HUANG ; Xiaoyan WANG ; Zhengwei HUANG ; Liuyan MENG ; Chen ZHANG ; Fangfang XIE ; Di YANG ; Jinhua YU ; Jin ZHAO ; Yihuai PAN ; Shuang PAN ; Deqin YANG ; Weidong NIU ; Qi ZHANG ; Shuli DENG ; Jingzhi MA ; Xiuping MENG ; Jian YANG ; Jiayuan WU ; Yi DU ; Junqi LING ; Lin YUE ; Xuedong ZHOU ; Qing YU
International Journal of Oral Science 2025;17(1):2-2
Apical microsurgery is accurate and minimally invasive, produces few complications, and has a success rate of more than 90%. However, due to the lack of awareness and understanding of apical microsurgery by dental general practitioners and even endodontists, many clinical problems remain to be overcome. The consensus has gathered well-known domestic experts to hold a series of special discussions and reached the consensus. This document specifies the indications, contraindications, preoperative preparations, operational procedures, complication prevention measures, and efficacy evaluation of apical microsurgery and is applicable to dentists who perform apical microsurgery after systematic training.
Microsurgery/standards*
;
Humans
;
Apicoectomy
;
Contraindications, Procedure
;
Tooth Apex/diagnostic imaging*
;
Postoperative Complications/prevention & control*
;
Consensus
;
Treatment Outcome
10.Expert consensus on management of instrument separation in root canal therapy.
Yi FAN ; Yuan GAO ; Xiangzhu WANG ; Bing FAN ; Zhi CHEN ; Qing YU ; Ming XUE ; Xiaoyan WANG ; Zhengwei HUANG ; Deqin YANG ; Zhengmei LIN ; Yihuai PAN ; Jin ZHAO ; Jinhua YU ; Zhuo CHEN ; Sijing XIE ; He YUAN ; Kehua QUE ; Shuang PAN ; Xiaojing HUANG ; Jun LUO ; Xiuping MENG ; Jin ZHANG ; Yi DU ; Lei ZHANG ; Hong LI ; Wenxia CHEN ; Jiayuan WU ; Xin XU ; Jing ZOU ; Jiyao LI ; Dingming HUANG ; Lei CHENG ; Tiemei WANG ; Benxiang HOU ; Xuedong ZHOU
International Journal of Oral Science 2025;17(1):46-46
Instrument separation is a critical complication during root canal therapy, impacting treatment success and long-term tooth preservation. The etiology of instrument separation is multifactorial, involving the intricate anatomy of the root canal system, instrument-related factors, and instrumentation techniques. Instrument separation can hinder thorough cleaning, shaping, and obturation of the root canal, posing challenges to successful treatment outcomes. Although retrieval of separated instrument is often feasible, it carries risks including perforation, excessive removal of tooth structure and root fractures. Effective management of separated instruments requires a comprehensive understanding of the contributing factors, meticulous preoperative assessment, and precise evaluation of the retrieval difficulty. The application of appropriate retrieval techniques is essential to minimize complications and optimize clinical outcomes. The current manuscript provides a framework for understanding the causes, risk factors, and clinical management principles of instrument separation. By integrating effective strategies, endodontists can enhance decision-making, improve endodontic treatment success and ensure the preservation of natural dentition.
Humans
;
Root Canal Therapy/adverse effects*
;
Consensus
;
Root Canal Preparation/adverse effects*

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