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.Reduced field-of-view diffusion weighted imaging for differentiating low-risk and high-risk thymoma
Chuyi TANG ; Jie LU ; Yeqi GAO ; Yan ZHONG ; Jie SHEN
Chinese Journal of Medical Imaging Technology 2024;40(12):1926-1930
Objective To observe the value of reduced field-of-view(rFOV)diffusion weighted imaging(DWI)for differentiating low-risk and high-risk thymoma.Methods A total of 145 patients with pathologically confirmed thymoma were retrospectively collected,among them there were 96 cases of low-risk thymoma(low-risk group,including 33 cases of type A,29 cases of type AB and 34 cases of type B1 thymoma)and 49 cases of high-risk thymoma(high-risk group,including 26 cases of type B2 and 23 cases of type B3 thymoma).Conventional single-shot echo planar imaging(SSEPI)and ZOOMit sequence DWI before treatment were compared,and subjective scoring based on displaying of anatomical structures,thymoma lesions,image artifacts and overall diagnosis confidence were performed,so did objective evaluation according to image signal-to-noise ratio(SNR)and contrast-to-noise ratio(CNR)of 2 kinds of images.The apparent diffusion coefficient(ADC)obtained with DWI were compared between groups.Receiver operating characteristic(ROC)curve was drawn,and area under the curve(AUC)was calculated to analyze the efficacy of ADC for differentiating low-risk and high-risk thymoma.Results Subjective scores of displaying anatomical structures,thymoma lesions,image artifacts and overall diagnosis confidence of ZOOMit were all superior to those of SSEPI(all P<0.001),while SNR and CNR of ZOOMit were both higher than those of SSEPI(all P<0.001).There were statistical differences of ADCSSEPI and ADCZOOMit between groups(both P<0.001).The AUC of ADCssEPI and ADCZOOMit for distinguishing low-risk and high-risk thymoma was 0.865 and 0.922,respectively,of the former was higher than of the latter(Z=2.091,P=0.037).Conclusion rFOV DWI could be used to differentiate low-risk and high-risk thymoma.
3.Reduced field-of-view diffusion weighted imaging for differentiating low-risk and high-risk thymoma
Chuyi TANG ; Jie LU ; Yeqi GAO ; Yan ZHONG ; Jie SHEN
Chinese Journal of Medical Imaging Technology 2024;40(12):1926-1930
Objective To observe the value of reduced field-of-view(rFOV)diffusion weighted imaging(DWI)for differentiating low-risk and high-risk thymoma.Methods A total of 145 patients with pathologically confirmed thymoma were retrospectively collected,among them there were 96 cases of low-risk thymoma(low-risk group,including 33 cases of type A,29 cases of type AB and 34 cases of type B1 thymoma)and 49 cases of high-risk thymoma(high-risk group,including 26 cases of type B2 and 23 cases of type B3 thymoma).Conventional single-shot echo planar imaging(SSEPI)and ZOOMit sequence DWI before treatment were compared,and subjective scoring based on displaying of anatomical structures,thymoma lesions,image artifacts and overall diagnosis confidence were performed,so did objective evaluation according to image signal-to-noise ratio(SNR)and contrast-to-noise ratio(CNR)of 2 kinds of images.The apparent diffusion coefficient(ADC)obtained with DWI were compared between groups.Receiver operating characteristic(ROC)curve was drawn,and area under the curve(AUC)was calculated to analyze the efficacy of ADC for differentiating low-risk and high-risk thymoma.Results Subjective scores of displaying anatomical structures,thymoma lesions,image artifacts and overall diagnosis confidence of ZOOMit were all superior to those of SSEPI(all P<0.001),while SNR and CNR of ZOOMit were both higher than those of SSEPI(all P<0.001).There were statistical differences of ADCSSEPI and ADCZOOMit between groups(both P<0.001).The AUC of ADCssEPI and ADCZOOMit for distinguishing low-risk and high-risk thymoma was 0.865 and 0.922,respectively,of the former was higher than of the latter(Z=2.091,P=0.037).Conclusion rFOV DWI could be used to differentiate low-risk and high-risk thymoma.

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