1.Dexmedetomidine Improves the Therapeutic Efficacy Against Mammary Tumors in Stress-exposed Mice by Inhibiting the TLR4/NF-κB Pathway
Chuyi ZHANG ; Shan MENG ; Xin XU ; Peng FAN ; Xunyuan MAO ; Yuhui HUANG ; Sanqing JIN
Journal of Sun Yat-sen University(Medical Sciences) 2026;47(4):601-612
ObjectiveThis study aimed to investigate whether dexmedetomidine (Dex) alleviates stress-induced mammary tumor progression in mice by inhibiting the TLR4/NF‑κB signaling pathway, and to examine its effects on anxiety‑depression‑like behaviors and stress hormone levels. MethodsAn orthotopic EMT6 mammary tumor model was established in mice, and chronic mild stress (CMS) was applied to induce anxiety‑depression‑like states. The mice were divided into six groups: naive, tumor, CMS, CMS+tumor, CMS+tumor+Dex, and CMS+tumor+Vehicle groups. Behavioral changes were evaluated using the open field test and tail suspension test. Plasma stress hormone levels were measured by high‑performance liquid chromatography. Western blot and RT‑qPCR were performed to detect the expression of TLR4, p‑NF‑κB p65, p‑IκBα, and inflammatory cytokines (IL‑6, IL‑1β, TNF‑α) in tumor tissues. In vitro, EMT6 cells were treated with cortisol to mimic the stress-related microenvironment, and the effects of Dex on the TLR4/NF‑κB pathway were assessed by CCK‑8, Western blot, and RT-qPCR. ResultsTumor‑bearing mice exhibited significant anxiety‑depression‑like behaviors (P<0.05), along with markedly elevated plasma levels of norepinephrine, epinephrine, and cortisol (P<0.05). Chronic stress further aggravated these behavioral abnormalities and promoted tumor growth (P<0.05). Dexmedetomidine intervention significantly improved anxiety‑depression‑like behaviors (P<0.05) and lowered peripheral stress hormone levels (P<0.05) in stress‑exposed tumor‑bearing mice. In vitro experiments demonstrated that cortisol treatment activated the TLR4/NF‑κB pathway (P<0.001) and upregulated the expression of inflammatory cytokines (P<0.05 in EMT6 cells, whereas dexmedetomidine effectively suppressed this activation (P<0.001). In the in vivo model, dexmedetomidine treatment downregulated the expression of TLR4, p‑NF‑κB p65, p‑IκBα, and pro‑inflammatory cytokines in tumor tissues (P<0.001) and significantly inhibited tumor growth (P<0.05). ConclusionDexmedetomidine inhibits the TLR4/NF‑κB signaling pathway, alleviates stress‑induced inflammatory responses, improves anxiety- and depression‑ like behaviors, reduces stress hormone levels, and suppresses mammary tumor progression. These findings provide an experimental basis for understanding anxiety- and depression- associated breast tumor progression and suggest that Dexmedetomidine and the TLR4/NF-κB pathway may serve as potential therapeutic targets.
2.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*
3.Glutamine signaling specifically activates c-Myc and Mcl-1 to facilitate cancer cell proliferation and survival.
Meng WANG ; Fu-Shen GUO ; Dai-Sen HOU ; Hui-Lu ZHANG ; Xiang-Tian CHEN ; Yan-Xin SHEN ; Zi-Fan GUO ; Zhi-Fang ZHENG ; Yu-Peng HU ; Pei-Zhun DU ; Chen-Ji WANG ; Yan LIN ; Yi-Yuan YUAN ; Shi-Min ZHAO ; Wei XU
Protein & Cell 2025;16(11):968-984
Glutamine provides carbon and nitrogen to support the proliferation of cancer cells. However, the precise reason why cancer cells are particularly dependent on glutamine remains unclear. In this study, we report that glutamine modulates the tumor suppressor F-box and WD repeat domain-containing 7 (FBW7) to promote cancer cell proliferation and survival. Specifically, lysine 604 (K604) in the sixth of the 7 substrate-recruiting WD repeats of FBW7 undergoes glutaminylation (Gln-K604) by glutaminyl tRNA synthetase. Gln-K604 inhibits SCFFBW7-mediated degradation of c-Myc and Mcl-1, enhances glutamine utilization, and stimulates nucleotide and DNA biosynthesis through the activation of c-Myc. Additionally, Gln-K604 promotes resistance to apoptosis by activating Mcl-1. In contrast, SIRT1 deglutaminylates Gln-K604, thereby reversing its effects. Cancer cells lacking Gln-K604 exhibit overexpression of c-Myc and Mcl-1 and display resistance to chemotherapy-induced apoptosis. Silencing both c-MYC and MCL-1 in these cells sensitizes them to chemotherapy. These findings indicate that the glutamine-mediated signal via Gln-K604 is a key driver of cancer progression and suggest potential strategies for targeted cancer therapies based on varying Gln-K604 status.
Glutamine/metabolism*
;
Myeloid Cell Leukemia Sequence 1 Protein/genetics*
;
Humans
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Proto-Oncogene Proteins c-myc/genetics*
;
Cell Proliferation
;
Signal Transduction
;
Neoplasms/pathology*
;
F-Box-WD Repeat-Containing Protein 7/genetics*
;
Cell Survival
;
Cell Line, Tumor
;
Apoptosis
4.Discriminating Tumor Deposits From Metastatic Lymph Nodes in Rectal Cancer: A Pilot Study Utilizing Dynamic Contrast-Enhanced MRI
Xue-han WU ; Yu-tao QUE ; Xin-yue YANG ; Zi-qiang WEN ; Yu-ru MA ; Zhi-wen ZHANG ; Quan-meng LIU ; Wen-jie FAN ; Li DING ; Yue-jiao LANG ; Yun-zhu WU ; Jian-peng YUAN ; Shen-ping YU ; Yi-yan LIU ; Yan CHEN
Korean Journal of Radiology 2025;26(5):400-410
Objective:
To evaluate the feasibility of dynamic contrast-enhanced MRI (DCE-MRI) in differentiating tumor deposits (TDs) from metastatic lymph nodes (MLNs) in rectal cancer.
Materials and Methods:
A retrospective analysis was conducted on 70 patients with rectal cancer, including 168 lesions (70 TDs and 98 MLNs confirmed by histopathology), who underwent pretreatment MRI and subsequent surgery between March 2019 and December 2022. The morphological characteristics of TDs and MLNs, along with quantitative parameters derived from DCE-MRI (K trans , kep, and v e) and DWI (ADCmin, ADCmax, and ADCmean), were analyzed and compared between the two groups.Multivariable binary logistic regression and receiver operating characteristic (ROC) curve analyses were performed to assess the diagnostic performance of significant individual quantitative parameters and combined parameters in distinguishing TDs from MLNs.
Results:
All morphological features, including size, shape, border, and signal intensity, as well as all DCE-MRI parameters showed significant differences between TDs and MLNs (all P < 0.05). However, ADC values did not demonstrate significant differences (all P > 0.05). Among the single quantitative parameters, v e had the highest diagnostic accuracy, with an area under the ROC curve (AUC) of 0.772 for distinguishing TDs from MLNs. A multivariable logistic regression model incorporating short axis, border, v e, and ADC mean improved diagnostic performance, achieving an AUC of 0.833 (P = 0.027).
Conclusion
The combination of morphological features, DCE-MRI parameters, and ADC values can effectively aid in the preoperative differentiation of TDs from MLNs in rectal cancer.
5.Discriminating Tumor Deposits From Metastatic Lymph Nodes in Rectal Cancer: A Pilot Study Utilizing Dynamic Contrast-Enhanced MRI
Xue-han WU ; Yu-tao QUE ; Xin-yue YANG ; Zi-qiang WEN ; Yu-ru MA ; Zhi-wen ZHANG ; Quan-meng LIU ; Wen-jie FAN ; Li DING ; Yue-jiao LANG ; Yun-zhu WU ; Jian-peng YUAN ; Shen-ping YU ; Yi-yan LIU ; Yan CHEN
Korean Journal of Radiology 2025;26(5):400-410
Objective:
To evaluate the feasibility of dynamic contrast-enhanced MRI (DCE-MRI) in differentiating tumor deposits (TDs) from metastatic lymph nodes (MLNs) in rectal cancer.
Materials and Methods:
A retrospective analysis was conducted on 70 patients with rectal cancer, including 168 lesions (70 TDs and 98 MLNs confirmed by histopathology), who underwent pretreatment MRI and subsequent surgery between March 2019 and December 2022. The morphological characteristics of TDs and MLNs, along with quantitative parameters derived from DCE-MRI (K trans , kep, and v e) and DWI (ADCmin, ADCmax, and ADCmean), were analyzed and compared between the two groups.Multivariable binary logistic regression and receiver operating characteristic (ROC) curve analyses were performed to assess the diagnostic performance of significant individual quantitative parameters and combined parameters in distinguishing TDs from MLNs.
Results:
All morphological features, including size, shape, border, and signal intensity, as well as all DCE-MRI parameters showed significant differences between TDs and MLNs (all P < 0.05). However, ADC values did not demonstrate significant differences (all P > 0.05). Among the single quantitative parameters, v e had the highest diagnostic accuracy, with an area under the ROC curve (AUC) of 0.772 for distinguishing TDs from MLNs. A multivariable logistic regression model incorporating short axis, border, v e, and ADC mean improved diagnostic performance, achieving an AUC of 0.833 (P = 0.027).
Conclusion
The combination of morphological features, DCE-MRI parameters, and ADC values can effectively aid in the preoperative differentiation of TDs from MLNs in rectal cancer.
6.Discriminating Tumor Deposits From Metastatic Lymph Nodes in Rectal Cancer: A Pilot Study Utilizing Dynamic Contrast-Enhanced MRI
Xue-han WU ; Yu-tao QUE ; Xin-yue YANG ; Zi-qiang WEN ; Yu-ru MA ; Zhi-wen ZHANG ; Quan-meng LIU ; Wen-jie FAN ; Li DING ; Yue-jiao LANG ; Yun-zhu WU ; Jian-peng YUAN ; Shen-ping YU ; Yi-yan LIU ; Yan CHEN
Korean Journal of Radiology 2025;26(5):400-410
Objective:
To evaluate the feasibility of dynamic contrast-enhanced MRI (DCE-MRI) in differentiating tumor deposits (TDs) from metastatic lymph nodes (MLNs) in rectal cancer.
Materials and Methods:
A retrospective analysis was conducted on 70 patients with rectal cancer, including 168 lesions (70 TDs and 98 MLNs confirmed by histopathology), who underwent pretreatment MRI and subsequent surgery between March 2019 and December 2022. The morphological characteristics of TDs and MLNs, along with quantitative parameters derived from DCE-MRI (K trans , kep, and v e) and DWI (ADCmin, ADCmax, and ADCmean), were analyzed and compared between the two groups.Multivariable binary logistic regression and receiver operating characteristic (ROC) curve analyses were performed to assess the diagnostic performance of significant individual quantitative parameters and combined parameters in distinguishing TDs from MLNs.
Results:
All morphological features, including size, shape, border, and signal intensity, as well as all DCE-MRI parameters showed significant differences between TDs and MLNs (all P < 0.05). However, ADC values did not demonstrate significant differences (all P > 0.05). Among the single quantitative parameters, v e had the highest diagnostic accuracy, with an area under the ROC curve (AUC) of 0.772 for distinguishing TDs from MLNs. A multivariable logistic regression model incorporating short axis, border, v e, and ADC mean improved diagnostic performance, achieving an AUC of 0.833 (P = 0.027).
Conclusion
The combination of morphological features, DCE-MRI parameters, and ADC values can effectively aid in the preoperative differentiation of TDs from MLNs in rectal cancer.
7.Discriminating Tumor Deposits From Metastatic Lymph Nodes in Rectal Cancer: A Pilot Study Utilizing Dynamic Contrast-Enhanced MRI
Xue-han WU ; Yu-tao QUE ; Xin-yue YANG ; Zi-qiang WEN ; Yu-ru MA ; Zhi-wen ZHANG ; Quan-meng LIU ; Wen-jie FAN ; Li DING ; Yue-jiao LANG ; Yun-zhu WU ; Jian-peng YUAN ; Shen-ping YU ; Yi-yan LIU ; Yan CHEN
Korean Journal of Radiology 2025;26(5):400-410
Objective:
To evaluate the feasibility of dynamic contrast-enhanced MRI (DCE-MRI) in differentiating tumor deposits (TDs) from metastatic lymph nodes (MLNs) in rectal cancer.
Materials and Methods:
A retrospective analysis was conducted on 70 patients with rectal cancer, including 168 lesions (70 TDs and 98 MLNs confirmed by histopathology), who underwent pretreatment MRI and subsequent surgery between March 2019 and December 2022. The morphological characteristics of TDs and MLNs, along with quantitative parameters derived from DCE-MRI (K trans , kep, and v e) and DWI (ADCmin, ADCmax, and ADCmean), were analyzed and compared between the two groups.Multivariable binary logistic regression and receiver operating characteristic (ROC) curve analyses were performed to assess the diagnostic performance of significant individual quantitative parameters and combined parameters in distinguishing TDs from MLNs.
Results:
All morphological features, including size, shape, border, and signal intensity, as well as all DCE-MRI parameters showed significant differences between TDs and MLNs (all P < 0.05). However, ADC values did not demonstrate significant differences (all P > 0.05). Among the single quantitative parameters, v e had the highest diagnostic accuracy, with an area under the ROC curve (AUC) of 0.772 for distinguishing TDs from MLNs. A multivariable logistic regression model incorporating short axis, border, v e, and ADC mean improved diagnostic performance, achieving an AUC of 0.833 (P = 0.027).
Conclusion
The combination of morphological features, DCE-MRI parameters, and ADC values can effectively aid in the preoperative differentiation of TDs from MLNs in rectal cancer.
8.Discriminating Tumor Deposits From Metastatic Lymph Nodes in Rectal Cancer: A Pilot Study Utilizing Dynamic Contrast-Enhanced MRI
Xue-han WU ; Yu-tao QUE ; Xin-yue YANG ; Zi-qiang WEN ; Yu-ru MA ; Zhi-wen ZHANG ; Quan-meng LIU ; Wen-jie FAN ; Li DING ; Yue-jiao LANG ; Yun-zhu WU ; Jian-peng YUAN ; Shen-ping YU ; Yi-yan LIU ; Yan CHEN
Korean Journal of Radiology 2025;26(5):400-410
Objective:
To evaluate the feasibility of dynamic contrast-enhanced MRI (DCE-MRI) in differentiating tumor deposits (TDs) from metastatic lymph nodes (MLNs) in rectal cancer.
Materials and Methods:
A retrospective analysis was conducted on 70 patients with rectal cancer, including 168 lesions (70 TDs and 98 MLNs confirmed by histopathology), who underwent pretreatment MRI and subsequent surgery between March 2019 and December 2022. The morphological characteristics of TDs and MLNs, along with quantitative parameters derived from DCE-MRI (K trans , kep, and v e) and DWI (ADCmin, ADCmax, and ADCmean), were analyzed and compared between the two groups.Multivariable binary logistic regression and receiver operating characteristic (ROC) curve analyses were performed to assess the diagnostic performance of significant individual quantitative parameters and combined parameters in distinguishing TDs from MLNs.
Results:
All morphological features, including size, shape, border, and signal intensity, as well as all DCE-MRI parameters showed significant differences between TDs and MLNs (all P < 0.05). However, ADC values did not demonstrate significant differences (all P > 0.05). Among the single quantitative parameters, v e had the highest diagnostic accuracy, with an area under the ROC curve (AUC) of 0.772 for distinguishing TDs from MLNs. A multivariable logistic regression model incorporating short axis, border, v e, and ADC mean improved diagnostic performance, achieving an AUC of 0.833 (P = 0.027).
Conclusion
The combination of morphological features, DCE-MRI parameters, and ADC values can effectively aid in the preoperative differentiation of TDs from MLNs in rectal cancer.
9.Value of MRI Ovarian-Adnexal Reporting and Data System in Differentiating Benign and Malignant Ovarian-Adnexal Lesions
Wen-hao FU ; Xiao-xiao HU ; Meng-ya SUN ; Fan ZHANG ; Ke WANG ; Guang-lei TANG ; Jian GUAN
Journal of Sun Yat-sen University(Medical Sciences) 2023;44(1):99-105
ObjectiveTo explore the value of MRI ovarian-adnexal reporting and data system (O-RADS MRI) in differentiating benign and malignant ovarian-adnexal masses.MethodsTotally 146 patients (202 masses) with ovarian-adnexal lesions who underwent pelvic examination at 3.0 T MRI according to standardized scan protocol of O-RADS MRI and were pathologically confirmed in The First Affiliated Hospital of Sun Yat-sen University between January 2020 and February 2022 were retrospectively analyzed. Two radiologists classified the ovarian-adnexal masses as risk levels 1~5 according to O-RADS MRI and evaluated their consistency by Cohen’s kappa. Using pathological findings as the gold standard, the detection yield of malignant lesions with O-RADS MRI classification was analyzed. Sensitivity, specificity, accuracy, and the area under the receiver operating characteristic curve were calculated (cutoff for malignancy, score ≥ 4).ResultsOf 202 masses, 62 (30.7%) were malignant, 140 (69.3%) were benign. The two radiologists presented good agreement in O-RADS MRI classification of ovarian adnexal masses (Kappa=0.932). The malignancy rates of masses with scores of 1, 2, 3, 4 and 5 were 0%, 0%, 7.7%, 95%, 97.6%, respectively. Sensitivity, specificity, accuracy, and the area under the receiver operating characteristic curve were 96.8% (60/62), 98.6% (138/140), 98.0% (198/202), 0.977.ConclusionsO-RADS MRI yields high diagnostic efficiency for benign and malignant ovarian adnexal masses and its widespread implementation will improve communication between radiologists and clinicians, and facilitate optimal patient management. Therefore, O-RADS MRI warrants widespread use in clinical setting.
10.Experts consensus on the procedure of dental operative microscope in endodontics and operative dentistry.
Bin LIU ; Xuedong ZHOU ; Lin YUE ; Benxiang HOU ; Qing YU ; Bing FAN ; Xi WEI ; Lihong QIU ; Zhengwei HUANG ; Wenwei XIA ; Zhe SUN ; Hanguo WANG ; Liuyan MENG ; Bin PENG ; Chen ZHANG ; Shuli DENG ; Zhaojie LU ; Deqin YANG ; Tiezhou HOU ; Qianzhou JIANG ; Xiaoli XIE ; Xuejun LIU ; Jiyao LI ; Zuhua WANG ; Haipeng LYU ; Ming XUE ; Jiuyu GE ; Yi DU ; Jin ZHAO ; Jingping LIANG
International Journal of Oral Science 2023;15(1):43-43
The dental operative microscope has been widely employed in the field of dentistry, particularly in endodontics and operative dentistry, resulting in significant advancements in the effectiveness of root canal therapy, endodontic surgery, and dental restoration. However, the improper use of this microscope continues to be common in clinical settings, primarily due to operators' insufficient understanding and proficiency in both the features and established operating procedures of this equipment. In October 2019, Professor Jingping Liang, Vice Chairman of the Society of Cariology and Endodontology, Chinese Stomatological Association, organized a consensus meeting with Chinese experts in endodontics and operative dentistry. The objective of this meeting was to establish a standard operation procedure for the dental operative microscope. Subsequently, a consensus was reached and officially issued. Over the span of about four years, the content of this consensus has been further developed and improved through practical experience.
Humans
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Dentistry, Operative
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Consensus
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Endodontics
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Root Canal Therapy
;
Dental Care

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