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.Predictive value of multi-modal conventional MRI radiomics for early postoperative glioma recurrence
Yuhui ZHANG ; Yingsi YANG ; Weixiong FAN ; Guihua JIANG ; Xiaoli XIONG ; Rihui YANG
Chinese Journal of Medical Physics 2025;42(2):208-212
Objective To explore the preoperative non-invasive prediction of early postoperative glioma recurrence using multi-modal conventional MRI radiomics.Methods A retrospective analysis of the clinical and MRI data of 83 glioma patients who met the inclusion criteria was conducted.The Kruskal-Wallis test was used to compare clinical factors between recurrent and non-recurrent groups.The automated segmentation of the entire tumor lesion for glioma patients was accomplished with VB-Net algorithm,a deep learning approach developed by United Imaging Healthcare;and the extraction of radiomics features from preoperative T1CE and T2WI images was carried out on URP platform.The optimal feature combination was determined using the maximum relevance and minimum redundancy and least absolute shrinkage and selection operator methods.Logistic regression and five-fold cross-validation were employed to analyze radiomics features and construct 4 prediction models,namely T2WI model,T1CE model,T2WI+T1CE model,and imaging-clinical fusion model.The diagnostic performances of these models were evaluated and compared using the area under the receiver operating characteristic curve(AUC)and the Delong test.In addition,the model sensitivity and specificity were calculated.Results Postoperatively,there were 40 recurrent cases and 43 non-recurrent cases.The clinical factors such as glioma grade showed statistical significance between two groups(P<0.05),while gender and age did not show significant statistical differences(P>0.05).For the single-sequence radiomics models,T1CE model(AUC:0.804)outperformed T2WI model(AUC:0.702).The multi-modal combined model exhibited a higher AUC than the single-sequence prediction models,with an AUC of 0.849,a sensitivity of 72.5%,and a specificity of 79.1%.The imaging-clinical fusion model whose predictive efficiency was close to that of multi-modal combined model(P=0.303)also performed well in forecasting postoperative glioma recurrence,with an AUC of 0.839,a sensitivity of 72.5%,and a specificity of 79.1%.Conclusion The multi-modal conventional MRI radiomics model can better predict early postoperative glioma recurrence.The imaging-clinical fusion model that includes glioma grade does not have the diagnostic performance superior to that of radiomics model.
3.Predicting microsatellite instability status in endometrial cancer based on whole-tumor apparent diffusion coefficient histogram
Tianhui ZHANG ; Xiumei DU ; Qiuming WANG ; Yuhui ZHANG ; Xi LONG ; Yingsi YANG ; Weixiong FAN
Journal of Practical Radiology 2025;41(10):1694-1698
Objective To investigate the value of predicting microsatellite instability(MSI)status in endometrial cancer based on whole-tumor apparent diffusion coefficient(ADC)histogram.Methods The data of 131 endometrial cancer patients who underwent preoperative MRI examination and were confirmed by pathology were retrospectively analyzed.According to the pathological immu-nohistochemical results,they were divided into microsatellite stability(MSS)group(103 cases)and MSI group(28 cases).The whole-tumor volume of interest(VOI)was outlined using ITK-SNAP software,and ADC histogram analysis was performed using uAI Research Portal software.The t-test or Mann-Whitney U-test were used to compare the differences between the two groups,and multifactorial logistic regression analysis was used to screen independent predictors for the above parameters with differences.The area under the curve(AUC),sensitivity and specificity were calculated using the receiver operating characteristic(ROC)curve.Results The ADC histogram parameters that were statistically significant between groups were ADC10th,ADC90th,ADCmaximum,ADCmedian,ADCmean,ADCrange,ADCinterquartile range,ADCuniformity,ADCvariance,ADCenergy,ADCentropy,ADCtotal energy,ADCroot mean square,ADCmean absolute deviation,ADCrobust mean absolute deviation,all the above parameters were significantly smaller in the MSI group than in the MSS group.Further multifactorial logistic regression analysis results showed that ADCmedian[odds ratio(OR)=1.019,P=0.020]and ADCroot mean square(OR=0.977,P=0.005)were independent predictors of the MSI status in endometrial cancer.The results of ROC curve showed that the AUC of ADCmedian and ADCroot mean square for predicting MSI status were 0.699 and 0.731,respectively,and the AUC of combining the two parameters to predict MSI status was 0.760,with a sensitivity of 57.14%and a specificity of 86.41%.Conclusion The parameters of ADCmedian and ADCroot mean square based on whole-tumor ADC histogram can be used to predict the MSI status of endometrial cancer,and the combined use of these two parameters helps to improve the efficacy of predicting MSI.
4.Incremental effectiveness of two-dose of mumps-containing vaccine in chidren
Chinese Journal of School Health 2025;46(6):883-887
Objective:
To evaluate the incremental vaccine effectiveness (VE) of two dose of the mumps containing vaccine (MuCV) in chidren, so as to provide a basis for optimizing mumps immunization strategies.
Methods:
A 1∶2 frequency matched case-control study was conducted by using reported mumps cases in childcare centers or schools from Lu an, Hefei, Ma anshan and Huainan cities of Anhui Province from September 1, 2023 to June 30, 2024, as a case group(383 cases). And healthy children in the same classroom were selected as a control group(766 cases). The MuCV immunization histories of participants were collected to estimate the incremental VE of the second dose of MuCV against mumps. Group comparisons were performed using the Chi square test or t-test. For matched case-control pairs, the Cox regression model was employed to calculate the odds ratio (OR) with 95% confidence interval (CI) for two dose MuCV vaccination and to estimate the incremental vaccine effectiveness (VE).
Results:
There were no statistically significant differences between the case and control groups regarding gender, age, dosage of MuCV vaccination and the time interval since the last dose vaccination( χ 2/t=0.05, 0.20, 0.94, -0.02, P >0.05). The proportions of the case and control groups vaccinated with two doses of MuCV were 26.63% and 29.37%, respectively, and the overall incremental VE of the second dose of MuCV was 40.73% (95% CI=3.03%-63.77%, P <0.05). Subgroup analyses revealed that the incremental VE for children with a period of ≥1 year between the two doses of MuCV was 54.13% (95% CI=1.90%-78.56%, P <0.05), while for children with a period of <1 year, it was 30.63% (95% CI=-28.59%-62.58%, P >0.05). The incremental VE of the second dose of MuCV was 30.36% (95% CI=-25.95%-61.50%, P >0.05) in kindergarten children and 66.73% (95% CI=14.92%-86.99%, P <0.05) in elementary and secondary school students. The incremental VE was 28.78% (95% CI=-27.46%-60.21%, P >0.05) within five years of the last dose of MuCV vaccination and 66.07% (95% CI=-41.56%-91.87%, P >0.05) for vaccinations administered beyond five years.
Conclusions
The second dose of MuCV may offer additional protection for children; however, extending the interval between two dose of MuCV (<1 year) has shown limited incremental protective effects. Therefore, it is crucial to consider optimizing current immunization strategies for mumps.
5.Predicting microsatellite instability status in endometrial cancer based on whole-tumor apparent diffusion coefficient histogram
Tianhui ZHANG ; Xiumei DU ; Qiuming WANG ; Yuhui ZHANG ; Xi LONG ; Yingsi YANG ; Weixiong FAN
Journal of Practical Radiology 2025;41(10):1694-1698
Objective To investigate the value of predicting microsatellite instability(MSI)status in endometrial cancer based on whole-tumor apparent diffusion coefficient(ADC)histogram.Methods The data of 131 endometrial cancer patients who underwent preoperative MRI examination and were confirmed by pathology were retrospectively analyzed.According to the pathological immu-nohistochemical results,they were divided into microsatellite stability(MSS)group(103 cases)and MSI group(28 cases).The whole-tumor volume of interest(VOI)was outlined using ITK-SNAP software,and ADC histogram analysis was performed using uAI Research Portal software.The t-test or Mann-Whitney U-test were used to compare the differences between the two groups,and multifactorial logistic regression analysis was used to screen independent predictors for the above parameters with differences.The area under the curve(AUC),sensitivity and specificity were calculated using the receiver operating characteristic(ROC)curve.Results The ADC histogram parameters that were statistically significant between groups were ADC10th,ADC90th,ADCmaximum,ADCmedian,ADCmean,ADCrange,ADCinterquartile range,ADCuniformity,ADCvariance,ADCenergy,ADCentropy,ADCtotal energy,ADCroot mean square,ADCmean absolute deviation,ADCrobust mean absolute deviation,all the above parameters were significantly smaller in the MSI group than in the MSS group.Further multifactorial logistic regression analysis results showed that ADCmedian[odds ratio(OR)=1.019,P=0.020]and ADCroot mean square(OR=0.977,P=0.005)were independent predictors of the MSI status in endometrial cancer.The results of ROC curve showed that the AUC of ADCmedian and ADCroot mean square for predicting MSI status were 0.699 and 0.731,respectively,and the AUC of combining the two parameters to predict MSI status was 0.760,with a sensitivity of 57.14%and a specificity of 86.41%.Conclusion The parameters of ADCmedian and ADCroot mean square based on whole-tumor ADC histogram can be used to predict the MSI status of endometrial cancer,and the combined use of these two parameters helps to improve the efficacy of predicting MSI.
6.Predictive value of multi-modal conventional MRI radiomics for early postoperative glioma recurrence
Yuhui ZHANG ; Yingsi YANG ; Weixiong FAN ; Guihua JIANG ; Xiaoli XIONG ; Rihui YANG
Chinese Journal of Medical Physics 2025;42(2):208-212
Objective To explore the preoperative non-invasive prediction of early postoperative glioma recurrence using multi-modal conventional MRI radiomics.Methods A retrospective analysis of the clinical and MRI data of 83 glioma patients who met the inclusion criteria was conducted.The Kruskal-Wallis test was used to compare clinical factors between recurrent and non-recurrent groups.The automated segmentation of the entire tumor lesion for glioma patients was accomplished with VB-Net algorithm,a deep learning approach developed by United Imaging Healthcare;and the extraction of radiomics features from preoperative T1CE and T2WI images was carried out on URP platform.The optimal feature combination was determined using the maximum relevance and minimum redundancy and least absolute shrinkage and selection operator methods.Logistic regression and five-fold cross-validation were employed to analyze radiomics features and construct 4 prediction models,namely T2WI model,T1CE model,T2WI+T1CE model,and imaging-clinical fusion model.The diagnostic performances of these models were evaluated and compared using the area under the receiver operating characteristic curve(AUC)and the Delong test.In addition,the model sensitivity and specificity were calculated.Results Postoperatively,there were 40 recurrent cases and 43 non-recurrent cases.The clinical factors such as glioma grade showed statistical significance between two groups(P<0.05),while gender and age did not show significant statistical differences(P>0.05).For the single-sequence radiomics models,T1CE model(AUC:0.804)outperformed T2WI model(AUC:0.702).The multi-modal combined model exhibited a higher AUC than the single-sequence prediction models,with an AUC of 0.849,a sensitivity of 72.5%,and a specificity of 79.1%.The imaging-clinical fusion model whose predictive efficiency was close to that of multi-modal combined model(P=0.303)also performed well in forecasting postoperative glioma recurrence,with an AUC of 0.839,a sensitivity of 72.5%,and a specificity of 79.1%.Conclusion The multi-modal conventional MRI radiomics model can better predict early postoperative glioma recurrence.The imaging-clinical fusion model that includes glioma grade does not have the diagnostic performance superior to that of radiomics model.
7.The value of multimodal MRI radiomics in predicting muscle-invasive bladder cancer
Yingsi YANG ; Xi LONG ; Xiaohong CHEN ; Rihui YANG ; Yuhui ZHANG ; Weixiong FAN ; Tianhui ZHANG
Journal of Practical Radiology 2024;40(2):249-252,274
Objective To investigate the value of multimodal MRI radiomics in predicting muscle-invasive bladder cancer.Methods A total of 178 patients with pathology diagnosis of bladder cancer were retrospectively collected,including 31 cases of muscle invasive bladder cancer(MIBC)and 147 cases of non-muscle invasive bladder cancer(NMIBC).Patients were randomly divided into training group and testing group at a ratio of 7︰3.The range of bladder tumors in T2WI,diffusion weighted imaging(DWI)and apparent diffusion coefficient(ADC)images were segmented as volume of interest(VOI)by using ITK-SNAP software.Radiomics features were extracted through A.K software.The optimal radiomics features were obtained through radiomics algorithm and least absolute shrinkage and selection operator(LASSO)method.Finally,the logistic regression analysis method and random forest model method were used to construct prediction models.The performance of prediction models was evaluated by the receiver operating characteristic(ROC)curve.Results This study constructed four groups of models containing T2WI prediction model,DWI prediction model,ADC prediction model,and T2WI+DWI+ADC prediction model.The area under the curve(AUC)of T2WI,DWI,and ADC prediction models for identifying MIBC and NMIBC were separately 0.920,0.914,and 0.954 in the training group while those were respectively 0.881,0.773,and 0.871 in the testing group.There was no statistical significance between T2WI,DWI,and ADC prediction models.In training and testing groups,the AUC of T2WI+DWI+ADC prediction model were respectively 0.959 and 0.909,which were higher than the single sequence prediction model.The sensitivity and specificity of the training group were 0.905 and 0.853 and the sensitivity and specificity of the testing group were 0.778 and 0.795.Conclusion MRI radiomics prediction model can effectively differentiate MIBC and NMIBC.The T2WI+DWI+ADC prediction model shows better prediction efficiency.
8.Establishment of a standardized daily behavior collection and analysis system for brain disease models of rhesus and cynomolgus monkeys and its application in autism spectrum disorder.
Xiaofeng REN ; Huimin WANG ; Xiaoman LV ; Yi ZHOU ; Yingyin FAN ; Yanjun YU ; Christoph W TURCK ; Yuhui CHEN ; Longbao LV ; Yingzhou HU ; Hao LI ; Wenchao WANG ; Dongdong QIN ; Xiaoli FENG ; Xintian HU
Journal of Zhejiang University. Science. B 2024;25(11):972-995
Complex brain diseases seriously endanger human health, and early diagnostic biomarkers and effective treatments are currently lacking. Due to ethical constraints on human research, establishing monkey models is crucial to address these issues. With the rapid development of technology, transgenic monkey models of a range of brain diseases, especially autism spectrum disorder (ASD), have been successfully established. However, to establish practical and effective brain disease models and subsequently apply them to disease mechanism and treatment studies, there is still a lack of a standard tool, i.e., a system for collecting and analyzing the daily behaviors of brain disease model monkeys. Therefore, with the goal of undertaking a comprehensive and quantitative study of behavioral phenotypes, we established a standard daily behavior collection and analysis system, including behavioral data collection protocols and a monkey daily behavior ethogram (MDBE) for rhesus and cynomolgus monkeys, which are the most commonly used non-human primates in model construction. Then, we used ASD as an application example after referring to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision (DSM-5-TR), which is widely used in clinical disease diagnosis to obtain ASD core clinical symptoms. We then established a sub-ethogram (ASD monkey core behavior ethogram (MCBE-ASD)) specifically for quantitative assessment of the core clinical symptoms of an ASD monkey model based on MDBE. Subsequently, we demonstrated the high reproducibility of the system.
Animals
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Autism Spectrum Disorder
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Macaca mulatta
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Disease Models, Animal
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Behavior, Animal
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Macaca fascicularis
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Male
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Humans
9.Mechanism of Qigui Didang Decoction in Treatment of Diabetic Kidney Disease Based on Network Pharmacology and Experimental Verification
Yuqin GUO ; Yuhui LU ; Lifei FAN ; Xiaomei CHEN ; Tingting HU ; Min LIN
World Science and Technology-Modernization of Traditional Chinese Medicine 2024;26(10):2648-2661
Objective To explore the mechanism of diabetic kidney disease(DKD)with Qigui Didang Decoction.Methods Using network pharmacology,the potential components and targets of Qigui Didang Decoction for DKD were obtained.The docking mode between the core target and key components was simulated with molecular docking technology.Finally,the effect of Qigui Didang Decoction on db/db mice was observed,and the mechanism of DKD improvement was verified from the level of in vivo experiment.Results 117 potential active ingredients,427 drug targets,and 2151 disease targets were obtained.KEGG enrichment analysis of 183 intersection targets revealed that the phosphatidylinositol 3 kinase(PI3K)/protein kinase B(PKB/Akt)signaling pathway may be one of the action pathways.Molecular docking revealed that AKT1 and TNF had strong binding forces with hederagenin,stigmasterol,and beta-sitosterol.In vivo,studies have shown that Qigui Didang Decoction improves the general conditions,renal function,blood glucose,and lipid levels in db/db mice,reverses kidney injury and necrosis,and significantly downregulates the protein expression of PI3K,p-Akt,and tumor necrosis factor-α(TNF-α)in db/db mice.Conclusion Qigui Didang Decoction plays a role in regulating glucose and lipid metabolism and inflammation,and promoting the activation of the PI3K/Akt signaling pathway may be an important mechanism.
10.The modified Bikini approach used for fixation of acetabular fracture with an integrated wing-shaped anatomical locking plate
Zhenhua ZHU ; Qiguang MAI ; Tao LI ; Haibo XIANG ; Yuhui CHEN ; Jianwen LIAO ; Shicai FAN
Chinese Journal of Orthopaedic Trauma 2024;26(3):194-201
Objective:To investigate the effectiveness of the modified Bikini approach in the fixation of acetabular fracture with an integrated wing-shaped anatomical locking plate.Methods:A retrospective study was conducted to analyze the data of 54 patients with acetabular fracture who had been treated at Department of Trauma Orthopedics, Orthopedic Medical Center, The Third Hospital Affiliated to Southern Medical University from May 2017 to June 2021. The patients were divided into 2 groups based on different surgical approaches: an observation group [26 cases, 6 males, 20 females; aged 40.0 (29.8, 46.8) years] treated with fixation with an integrated wing-shaped anatomical locking plate through the modified Bikini approach, and a control group [28 cases, 10 males, 18 females; aged 34.5 (24.0, 43.5) years] treated with fixation with an integrated wing-shaped anatomical locking plate through the lateral-rectus approach. The incision length, operation time, intraoperative bleeding, length of hospital stay, quality of postoperative fracture reduction, visual analog scale (VAS) for pain, hip function, Vancouver Scar Scale (VSS) and Patient and Observer Scar Assessment Scale (POSAS) were compared between the 2 groups.Results:The differences in the preoperative general data between the 2 groups were not statistically significant, indicating comparability ( P>0.05). There were no statistically significant differences between the 2 groups either in terms of incision length, operation time, intraoperative bleeding, or hospital stay ( P>0.05). The 2 groups were not significantly different in the excellent/good rate of fracture reduction [100.0% (26/26) versus 92.9% (26/28)], VAS at 1 month postoperation [2.0(1.0, 3.0) versus 2.0(1.0, 3.0)], or the modified Merle d'Aubigné and Postel hip score at 12 months postoperation [13.5(12.3, 14.8) versus. 14.0(13.0, 15.0)] ( P>0.05). However, the VSS [4.50(4.00, 6.00)] and POSAS (29.85±10.05) at 12 months postoperation in the observation group were significantly lower than those in the control group [6.50(5.00, 8.25) and 37.11±11.75] ( P<0.05). Conclusion:In the fixation of acetabular fracture with an integrated wing-shaped anatomical locking plate, the modified Bikini approach can not only achieve as fine early clinical efficacy as the lateral-rectus approach, but also demonstrate the aesthetic advantages of smaller incision scar and more hidden incision.


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