1.RXRα modulates hepatic stellate cell activation and liver fibrosis by targeting CaMKKβ-AMPKα axis.
Lijun CAI ; Meimei YIN ; Shuangzhou PENG ; Fen LIN ; Liangliang LAI ; Xindao ZHANG ; Lei XIE ; Chuanying WANG ; Huiying ZHOU ; Yunfeng ZHAN ; Gulimiran ALITONGBIEKE ; Baohuan LIAN ; Zhibin SU ; Tenghui LIU ; Yuqi ZHOU ; Zongxi LI ; Xiaohui CHEN ; Qi ZHAO ; Ting DENG ; Lulu CHEN ; Jingwei SU ; Luoyan SHENG ; Ying SU ; Ling-Juan ZHANG ; Fu-Quan JIANG ; Xiao-Kun ZHANG
Acta Pharmaceutica Sinica B 2025;15(7):3611-3631
Hepatic stellate cells (HSCs) are the primary fibrogenic cells in the liver, and their activation plays a crucial role in the development and progression of hepatic fibrosis. Here, we report that retinoid X receptor-alpha (RXRα), a unique member of the nuclear receptor superfamily, is a key modulator of HSC activation and liver fibrosis. RXRα exerts its effects by modulating calcium/calmodulin-dependent protein kinase kinase β (CaMKKβ)-mediated activation of AMP-activated protein kinase-alpha (AMPKα). In addition, we demonstrate that K-80003, which binds RXRα by a unique mechanism, effectively suppresses HSC activation, proliferation, and migration, thereby inhibiting liver fibrosis in the CCl4 and amylin liver NASH (AMLN) diet animal models. The effect is mediated by AMPKα activation, promoting mitophagy in HSCs. Mechanistically, K-80003 activates AMPKα by inducing RXRα to form condensates with CaMKKβ and AMPKα via a two-phase process. The formation of RXRα condensates is driven by its N-terminal intrinsic disorder region and requires phosphorylation by CaMKKβ. Our results reveal a crucial role of RXRα in liver fibrosis regulation through modulating mitochondrial activities in HSCs. Furthermore, they suggest that K-80003 and related RXRα modulators hold promise as therapeutic agents for fibrosis-related diseases.
2.Multimodal imaging evaluation of the early efficacy of 90Y microsphere selective internal radiation therapy for liver malignant tumors
Fangyun ZHONG ; Lijuan YU ; Yujun WANG ; Hui ZHOU ; Haoyu LIU ; Zhouyang SONG ; Deng PAN ; Yuqi LU
Chinese Journal of Nuclear Medicine and Molecular Imaging 2025;45(6):325-329
Objective:To compare the value of different imaging modalities in evaluating early efficacy of 90Y-selective internal radiation therapy (SIRT) for liver malignant tumors. Methods:From September 2021 to December 2023, a retrospective analysis was conducted on 43 patients (32 males, 11 females; age (55.8±14.7) years) with liver malignant tumors who received 90Y-SIRT at Hainan Cancer Hospital and Boao Super Hospital. The injection dosage of 90Y was 1.5(1.2, 2.4)GBq. Clinical and imaging data of patients before and after treatment for multimodal evaluation were collected, including MRI plain and enhanced scans, as well as diffusion weighted imaging (DWI). Plain scan images were evaluated for the treatment efficacy by response evaluation criteria in solid tumors (RECIST) 1.1 version, while enhanced MRI was scored into 1-5 based on changes in the target area, including increased low-density range, necrotic features, and decreased enhancement. The minimum apparent diffusion coefficient (ADC min) of DWI increased by 20% compared to baseline was determined to be responsive. Wilcoxon signed rank test was used to analyze data, and ROC curve analysis was used to analyze the diagnostic efficacy of different imaging modalities (Delong test). Results:All patients had baseline MRI data, 39 underwent MRI at 1-month after treatment, and 22 underwent MRI at 3-month after treatment. Based on MRI plain scan images, the target lesions showed partial remission (PR) in 10.26%(4/39) of patients, progressive disease (PD) in 5.13%(2/39) of patients, and stable disease (SD) in 84.61%(33/39) of patients at 1-month after treatment; while there were 40.91%(9/22) PR, 9.09%(2/22) PD and 50.00%(11/22) SD at 3-month after treatment. Based on DWI images, 35.90%(14/39) and 68.18%(15/22) of patients were considered responsive at 1-month and 3-month after treatment, respectively. Compared with baseline, the differences of tumor sizes, enhancement degree of target lesions and ADC min at 1-month and 3-month after treatment were statistically significant ( Z values: from -3.88 to -2.39, all P<0.05). Compared with the tumor size and enhancement degree, the AUCs of ADC min were the highest at 1-month (0.701) and 3-month (0.953) after treatment ( Z values: 0.40-2.29, all P<0.05). Conclusions:MRI plain scan, MRI enhancement and DWI are effective in the evaluation the efficacy of 90Y-SIRT for liver malignant tumors at 1-month and 3-month after treatment. ADC min is superior to tumor size and enhancement degree in diagnostic efficacy.
3.Predictive Value of a Multidimensional Neonatal Nutritional Risk Screening Scale for Extrauterine Growth Restriction in Premature Infants
Yumei WU ; Juntao ZHANG ; Yinghong DENG ; Yuqi LI ; Huan FENG ; Jie WU
Journal of Kunming Medical University 2025;46(3):72-78
Objective To apply a multidimensional neonatal nutritional risk screening scale for hospitalized premature infants to explore its predictive value for extrauterine growth restriction(EUGR)at the time of discharge.Methods A total of 104 premature infants hospitalized in the Neonatal Department of the Second Affiliated Hospital of Kunming Medical University from January 2023 to September 2023 were selected as research subjects.Nutritional risk screening was conducted within 24 hours of admission and weekly thereafter using the multidimensional neonatal nutritional risk screening scale.Scoring was based on four dimensions(birth status,weight changes,nutritional intake methods,and disease diagnosis),with a total score of ≥ 8 indicating high risk;≥4 and<8 indicating moderate risk;and<4 indicating low risk.EUGR at the time of discharge was the primary clinical outcome indicator.Receiver operating characteristic(ROC)curves were constructed to explore the predictive value of neonatal nutritional risk screening for EUGR in premature infants.Results At discharge,40 premature infants(38.5%)experienced EUGR.The nutritional risk screening scores of the EUGR group on day 7 of hospitalization were higher than those of the non-EUGR group(P<0.05).The rate of high nutritional risk on day 7 of hospitalization was highest(7.9%in the non-EUGR group,22%in the EUGR group,and 13.5%overall).On both day 1 and day 7 of hospitalization,the rate of high nutritional risk in the EUGR group was higher than that in the non-EUGR group(P<0.05).There were significant differences in the nutritional risk screening scores on day 7,birth weight Z-scores,discharge corrected gestational age weight Z-scores,and serum albumin levels between the EUGR and non-EUGR groups(P<0.05).ROC curves were plotted,yielding AUCs of 0.625(95%CI 0.514,0.736),0.652(95%CI 0.544,0.760),0.674(95%CI 0.561,0.786),and 0.641(95%CI 0.531,0.750),indicating certain predictive value.A combined predictive ROC model yielded an AUC of 0.786(95%CI 0.692,0.880)for EUGR,which was higher than the AUCs for individual indicators(P<0.001).Conclusion The occurrence of EUGR is relatively common among hospitalized premature infants.The nutritional risk is highest during the first week of hospitalization.The multidimensional neonatal nutritional risk screening scale can dynamically assess nutritional risk during hospitalization and may serve as one of the early warning indicators for EUGR in premature infants.The predictive efficacy for EUGR is enhanced when combined with birth weight Z-scores,discharge weight Z-scores,and serum albumin,providing a basis for individualized nutritional management of premature infants.
4.Impact of 5G remote robotic cholecystectomy on postoperative rehabilitation and quality of life in patients with gallstones
Yuqi MA ; Ming HU ; Yuan DENG ; Jing YANG ; Jin GUO ; Zeping ZHANG ; Wutang JING ; Weipeng ZHAN ; Hui CAI ; Yuntao MA
Chinese Journal of General Surgery 2025;40(7):528-532
Objective:To evaluate the effect of 5th generation mobile communication technology(5G) remote robot-assisted cholecystectomy on postoperative recovery and quality of life in patients with gallstones.Methods:Clinical data of patients who underwent 5G remote robotic cholecystectomy(20 cases) vs traditional robotic cholecystectomy(20 cases) at Gansu Provincial People's Hospital from May to September 2023 were retrospectively analyzed. Intraoperative and postoperative related indexes were compared between the two groups, and changes in pain analog scores before, 12 hours, and 24 hours after surgery, and global quality of life (GIQLI) scores before and 3 months after surgery were evaluated.Results:There was no significant difference between the two groups in terms of intraoperative and postoperative conditions (intraoperative blood loss, operative time, time to exhaustion, and length of hospital stay). Patients' pain analog scores at 12 and 24 hours postoperatively were lower than preoperatively, but the differences were not statistically significant( P>0.05). In addition, there was no significant difference in recovery indicators between the two groups compared to the control group ( P>0.05). Conclusion:The postoperative recovery metrics of 5G tele-robotic-assisted cholecystectomy were consistent with the results of conventional robotic surgery.
5.Prognostic value of single PET-CT after chemotherapy combined with immunotherapy in patients with non-small cell lung cancer treated with radiotherapy
Zhenghui MA ; Yuqi WU ; Guangqian JI ; Zongmei ZHOU ; Qinfu FENG ; Zefen XIAO ; Jima LYU ; Xin WANG ; Jianyang WANG ; Wenyang LIU ; Lei DENG ; Wenqing WANG ; Nan BI ; Junlin YI ; Tao ZHANG
Chinese Journal of Radiation Oncology 2025;34(11):1111-1116
Objective:To evaluate the role of a single PET-CT scan in predicting survival and prognosis in patients with non-small cell lung cancer (NSCLC) who did not undergo surgery but received radiotherapy after neoadjuvant chemotherapy combined with immunotherapy.Methods:A retrospective analysis was conducted on the data of 23 NSCLC patients treated at the Cancer Hospital of the Chinese Academy of Medical Sciences from May 2022 to June 2024. All patients were pathologically confirmed, received neoadjuvant chemotherapy combined with immunotherapy, did not undergo surgery for various reasons, and instead received radiotherapy. Each patient underwent only one PET-CT scan after neoadjuvant chemotherapy combined with immunotherapy and before radiotherapy. According to the maximum standardized uptake value (SUV max) on PET-CT, patients were divided into the low-uptake group (SUV max < 8, n=12) and high-uptake group (SUV max ≥ 8, n=11). Survival analysis was performed using the Kaplan-Meier method with survival curves plotted. Univariate analysis of influencing factors of survival was conducted using the Cox proportional hazards regression model. Clinical characteristics and survival outcomes of the two groups were compared, including progression-free survival (PFS) and overall survival (OS). Results:The 1-year PFS rates were 100% in the low-uptake group, 54.5% in the high-uptake group. This difference was statistically significant ( P=0.007). The 1-year and 2-year OS rates were both 100% in the low-uptake group, the 1-year and 2-year OS rates were both 90.9% in the high-uptake group, with no statistically significant difference ( P=0.394). Univariate Cox analysis identified age as an independent factor affecting PFS. Conclusions:For NSCLC patients who did not undergo surgical resection but received radiotherapy after neoadjuvant chemotherapy combined with immunotherapy, a single PET-CT scan before radiotherapy has potential value in predicting PFS. However, clinical studies with larger sample size and longer follow-up are required to evaluate its predictive value for OS.
6.Epidemiological characteristics and prediction model of bacillary dysentery in Qinghai Province,2014-2023
Yuqi JIANG ; Jinhua ZHAO ; Jiang LONG ; Yang ZHANG ; Ping DENG ; Sheng-lin QIN ; Huayi ZHANG
Chinese Journal of Infection Control 2025;24(10):1389-1394
Objective To compare five time series models and predict the monthly incidence of bacillary dysentery in Qinghai Province in 2024,and provide reference for the prevention and control.Methods The epidemic charac-teristics of bacterial dysentery in Qinghai Province from 2014 to 2023 were analyzed.R4.3.1 software was used for establishing seasonal autoregressive integrated moving average(SARIMA)model,Holt-Winters triple exponential smoothing(Holt Winters)model,exponential smoothing(ETS)model,neural network autoregression(NNAR)model,and trigonometric seasonality,Box-Cox transformation,ARMA errors,trend and seasonal components(TBATS)model.Fitting effect of the models was analyzed and accuracy was compared.Results From 2014 to 2023,a total of 5 833 cases of bacterial dysentery were reported in Qinghai Province,without deaths,male to fe-male ratio being 1.23∶1.The highest incidence was reported in 2016(15.45 per 100 000 people),and the lowest in-cidence was reported in 2023(3.68 per 100 000 people).Incidence increased from 2014 to 2016,then decreased,showing an obvious overall downward trend.Case number in<5 years age group was the highest,accounting for 29.76%of the total cases(n=1 736).Regarding population distribution,the top three were children in childcare institutions and scattered children(35.56%),farmers(24.65%),and students(12.62%).Except the additive Holt-Winters model,the predicted trends of the other four models were consistent with actuality.The ETS model had the best fitting effect,with a relatively balanced overall performance(training set:MAE=0.13,RMSE=0.21,MAPE=19.55%;testing set:MAE=0.11,RMSE=0.16,MAPE=28.66%).It is recommended to pre-dict the incidence of bacillary dysentery in Qinghai Province based on ETS model.Conclusion From 2014 to 2023,bacterial dysentery in Qinghai Province showed a downward trend,with the peak of the epidemic from June to Au-gust.Preschool and scattered children were high-risk groups.Among the five prediction models,ETS model has the best fitting effect,and can be used to predict the incidence of bacillary dysentery.
7.Epidemiological characteristics and prediction model of bacillary dysentery in Qinghai Province,2014-2023
Yuqi JIANG ; Jinhua ZHAO ; Jiang LONG ; Yang ZHANG ; Ping DENG ; Sheng-lin QIN ; Huayi ZHANG
Chinese Journal of Infection Control 2025;24(10):1389-1394
Objective To compare five time series models and predict the monthly incidence of bacillary dysentery in Qinghai Province in 2024,and provide reference for the prevention and control.Methods The epidemic charac-teristics of bacterial dysentery in Qinghai Province from 2014 to 2023 were analyzed.R4.3.1 software was used for establishing seasonal autoregressive integrated moving average(SARIMA)model,Holt-Winters triple exponential smoothing(Holt Winters)model,exponential smoothing(ETS)model,neural network autoregression(NNAR)model,and trigonometric seasonality,Box-Cox transformation,ARMA errors,trend and seasonal components(TBATS)model.Fitting effect of the models was analyzed and accuracy was compared.Results From 2014 to 2023,a total of 5 833 cases of bacterial dysentery were reported in Qinghai Province,without deaths,male to fe-male ratio being 1.23∶1.The highest incidence was reported in 2016(15.45 per 100 000 people),and the lowest in-cidence was reported in 2023(3.68 per 100 000 people).Incidence increased from 2014 to 2016,then decreased,showing an obvious overall downward trend.Case number in<5 years age group was the highest,accounting for 29.76%of the total cases(n=1 736).Regarding population distribution,the top three were children in childcare institutions and scattered children(35.56%),farmers(24.65%),and students(12.62%).Except the additive Holt-Winters model,the predicted trends of the other four models were consistent with actuality.The ETS model had the best fitting effect,with a relatively balanced overall performance(training set:MAE=0.13,RMSE=0.21,MAPE=19.55%;testing set:MAE=0.11,RMSE=0.16,MAPE=28.66%).It is recommended to pre-dict the incidence of bacillary dysentery in Qinghai Province based on ETS model.Conclusion From 2014 to 2023,bacterial dysentery in Qinghai Province showed a downward trend,with the peak of the epidemic from June to Au-gust.Preschool and scattered children were high-risk groups.Among the five prediction models,ETS model has the best fitting effect,and can be used to predict the incidence of bacillary dysentery.
8.Multimodal imaging evaluation of the early efficacy of 90Y microsphere selective internal radiation therapy for liver malignant tumors
Fangyun ZHONG ; Lijuan YU ; Yujun WANG ; Hui ZHOU ; Haoyu LIU ; Zhouyang SONG ; Deng PAN ; Yuqi LU
Chinese Journal of Nuclear Medicine and Molecular Imaging 2025;45(6):325-329
Objective:To compare the value of different imaging modalities in evaluating early efficacy of 90Y-selective internal radiation therapy (SIRT) for liver malignant tumors. Methods:From September 2021 to December 2023, a retrospective analysis was conducted on 43 patients (32 males, 11 females; age (55.8±14.7) years) with liver malignant tumors who received 90Y-SIRT at Hainan Cancer Hospital and Boao Super Hospital. The injection dosage of 90Y was 1.5(1.2, 2.4)GBq. Clinical and imaging data of patients before and after treatment for multimodal evaluation were collected, including MRI plain and enhanced scans, as well as diffusion weighted imaging (DWI). Plain scan images were evaluated for the treatment efficacy by response evaluation criteria in solid tumors (RECIST) 1.1 version, while enhanced MRI was scored into 1-5 based on changes in the target area, including increased low-density range, necrotic features, and decreased enhancement. The minimum apparent diffusion coefficient (ADC min) of DWI increased by 20% compared to baseline was determined to be responsive. Wilcoxon signed rank test was used to analyze data, and ROC curve analysis was used to analyze the diagnostic efficacy of different imaging modalities (Delong test). Results:All patients had baseline MRI data, 39 underwent MRI at 1-month after treatment, and 22 underwent MRI at 3-month after treatment. Based on MRI plain scan images, the target lesions showed partial remission (PR) in 10.26%(4/39) of patients, progressive disease (PD) in 5.13%(2/39) of patients, and stable disease (SD) in 84.61%(33/39) of patients at 1-month after treatment; while there were 40.91%(9/22) PR, 9.09%(2/22) PD and 50.00%(11/22) SD at 3-month after treatment. Based on DWI images, 35.90%(14/39) and 68.18%(15/22) of patients were considered responsive at 1-month and 3-month after treatment, respectively. Compared with baseline, the differences of tumor sizes, enhancement degree of target lesions and ADC min at 1-month and 3-month after treatment were statistically significant ( Z values: from -3.88 to -2.39, all P<0.05). Compared with the tumor size and enhancement degree, the AUCs of ADC min were the highest at 1-month (0.701) and 3-month (0.953) after treatment ( Z values: 0.40-2.29, all P<0.05). Conclusions:MRI plain scan, MRI enhancement and DWI are effective in the evaluation the efficacy of 90Y-SIRT for liver malignant tumors at 1-month and 3-month after treatment. ADC min is superior to tumor size and enhancement degree in diagnostic efficacy.
9.Impact of 5G remote robotic cholecystectomy on postoperative rehabilitation and quality of life in patients with gallstones
Yuqi MA ; Ming HU ; Yuan DENG ; Jing YANG ; Jin GUO ; Zeping ZHANG ; Wutang JING ; Weipeng ZHAN ; Hui CAI ; Yuntao MA
Chinese Journal of General Surgery 2025;40(7):528-532
Objective:To evaluate the effect of 5th generation mobile communication technology(5G) remote robot-assisted cholecystectomy on postoperative recovery and quality of life in patients with gallstones.Methods:Clinical data of patients who underwent 5G remote robotic cholecystectomy(20 cases) vs traditional robotic cholecystectomy(20 cases) at Gansu Provincial People's Hospital from May to September 2023 were retrospectively analyzed. Intraoperative and postoperative related indexes were compared between the two groups, and changes in pain analog scores before, 12 hours, and 24 hours after surgery, and global quality of life (GIQLI) scores before and 3 months after surgery were evaluated.Results:There was no significant difference between the two groups in terms of intraoperative and postoperative conditions (intraoperative blood loss, operative time, time to exhaustion, and length of hospital stay). Patients' pain analog scores at 12 and 24 hours postoperatively were lower than preoperatively, but the differences were not statistically significant( P>0.05). In addition, there was no significant difference in recovery indicators between the two groups compared to the control group ( P>0.05). Conclusion:The postoperative recovery metrics of 5G tele-robotic-assisted cholecystectomy were consistent with the results of conventional robotic surgery.
10.Prognostic value of single PET-CT after chemotherapy combined with immunotherapy in patients with non-small cell lung cancer treated with radiotherapy
Zhenghui MA ; Yuqi WU ; Guangqian JI ; Zongmei ZHOU ; Qinfu FENG ; Zefen XIAO ; Jima LYU ; Xin WANG ; Jianyang WANG ; Wenyang LIU ; Lei DENG ; Wenqing WANG ; Nan BI ; Junlin YI ; Tao ZHANG
Chinese Journal of Radiation Oncology 2025;34(11):1111-1116
Objective:To evaluate the role of a single PET-CT scan in predicting survival and prognosis in patients with non-small cell lung cancer (NSCLC) who did not undergo surgery but received radiotherapy after neoadjuvant chemotherapy combined with immunotherapy.Methods:A retrospective analysis was conducted on the data of 23 NSCLC patients treated at the Cancer Hospital of the Chinese Academy of Medical Sciences from May 2022 to June 2024. All patients were pathologically confirmed, received neoadjuvant chemotherapy combined with immunotherapy, did not undergo surgery for various reasons, and instead received radiotherapy. Each patient underwent only one PET-CT scan after neoadjuvant chemotherapy combined with immunotherapy and before radiotherapy. According to the maximum standardized uptake value (SUV max) on PET-CT, patients were divided into the low-uptake group (SUV max < 8, n=12) and high-uptake group (SUV max ≥ 8, n=11). Survival analysis was performed using the Kaplan-Meier method with survival curves plotted. Univariate analysis of influencing factors of survival was conducted using the Cox proportional hazards regression model. Clinical characteristics and survival outcomes of the two groups were compared, including progression-free survival (PFS) and overall survival (OS). Results:The 1-year PFS rates were 100% in the low-uptake group, 54.5% in the high-uptake group. This difference was statistically significant ( P=0.007). The 1-year and 2-year OS rates were both 100% in the low-uptake group, the 1-year and 2-year OS rates were both 90.9% in the high-uptake group, with no statistically significant difference ( P=0.394). Univariate Cox analysis identified age as an independent factor affecting PFS. Conclusions:For NSCLC patients who did not undergo surgical resection but received radiotherapy after neoadjuvant chemotherapy combined with immunotherapy, a single PET-CT scan before radiotherapy has potential value in predicting PFS. However, clinical studies with larger sample size and longer follow-up are required to evaluate its predictive value for OS.

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