1.PRMT1-mediated asymmetric dimethylation of arginine residue 602 in DDX1 promotes cholangiocarcinoma progression
Wenzheng LIU ; Yangwei LIAO ; Yiyang KUAI ; Xin GAO ; Xingmin YAN ; Jingjing LI ; Junsheng CHEN ; Jukun SU ; Jingcong ZHOU ; Yizhu KONG ; Siqin HUANG ; Zhiwei ZHANG ; Feng PENG ; Bing WANG ; Yongjun CHEN
Clinical and Molecular Hepatology 2026;32(2):843-865
Background/Aims:
Cholangiocarcinoma (CCA) is a primary malignant neoplasm with an extremely poor prognosis. While combined chemoradiotherapy has been demonstrated to delay CCA progression to a certain extent, the absence of specific molecular biomarkers or targets significantly hinders the diagnosis and treatment of CCA.
Methods:
Through cross-analysis of proteomics and ADMA modificationomics, we identified DDX1 overexpressed in CCA with elevated R602-ADMA modifications. HPLC-MS/MS identified PRMT1 as the methyltransferase and USP10 as the deubiquitinating enzyme for DDX1. Immunofluorescence and nuclear-cytoplasmic partitioning experiments confirmed DDX1’s nuclear localization. GO and KEGG analyses clarify the biological functions of DDX1 in response to hypoxia. RNA-seq transcriptomics analyzed key pathways influenced by DDX1. A hydrodynamic in situ CCA mouse model was established to validate the chemopreventive effects of the PRMT1-specific inhibitor GSK715 on CCA development.
Results:
DDX1 promotes CCA progression both in vivo and in vitro and can be inhibited by GSK715. Mechanistically, PRMT1 mediates ADMA modification at position R602 of DDX1. This modification promotes DDX1 nuclear localization by recruiting USP10 to deubiquitinate DDX1, while simultaneously inhibiting PRMT1 degradation. DDX1 promotes the transcription of PRMT1 and USP10 by binding to the mRNA 3’UTR region, establishing a positive feedback regulatory pathway. This mechanism promotes the occurrence and development of CCA and can serve as a target for the inhibitor GSK715 to suppress CCA progression.
Conclusions
Our study identified DDX1-R602-ADMA modification as a novel ADMA modification in CCA. It further confirmed its pivotal role in CCA progression. Targeting the USP10-PRMT1-DDX1 axis may represent a significant therapeutic approach for CCA.
2.Current Research Status of Digital Technology in the Rehabilitation of Rare Neurological and Muscular Diseases
Yixuan GUO ; Yi GAO ; Yiyang YAO ; Zhuoyue QIN ; Yaofang ZHANG ; Jiaqi JING ; Jing XIE ; Jian GUO ; Shuyang ZHANG
JOURNAL OF RARE DISEASES 2025;4(1):122-131
To review the randomized controlled trials (RCTs) at home and abroad on digital intelligence (DI)-driven rehabilitation in patients of neuromuscular disease, compare the effects of DI-driven rehabilitation with traditional rehabilitation, summarize the special needs and challenges faced by patients in rehabilitation of rare neuromuscular diseases, and provide evidence for the development and quality improvement of rehabilitation for rare neuromuscular diseases. We searched PubMed, Web of Science, Embase, CNKI, VIP, and Wanfang databases for literature on neuromuscular diseases, rare diseases, digital and intelligent technologies, and rehabilitation published from the inception of the databases to June 2024. Basic and research-related information from the retrieved literature was extracted and analyzed. A total of 43 RCTs in English from 14 countries were included. The most studied diseases were Parkinson′s disease and multiple sclerosis. The application of DI-driven technologies in rehabilitation of rare neuromuscular diseases was still limited. The commonly used technologies were virtual reality (VR) games, intelligent treadmill assistance, gait training robots, hybrid assistive limb (HAL), wearable sensors and tele-rehabilitation (TR) systems. These technologies were applied in patients′ homes or rehabilitation service centers. The VR games significantly improved both static/dynamic balance functions and cognitive functions. The intelligent treadmill assistance significantly enhanced gait speed and stride length. The gait training robots significantly improved balance, gait speed and stride length of patients. The wearable exoskeletons significantly enhanced walking ability. DI-driven rehabilitation measures have great value and potential in the field of neuromuscular disease rehabilitation. Their advantages and characteristics can meet the diverse needs of rare disease patients. In the future, a hierarchical and collaborative rehabilitation service system should be established to meet the urgent needs of the rehabilitation of rare neuromuscular diseases. Combining the advantages of digitization and intelligence will provide standardized, scientific, convenient and affordable rehabilitation services to patients.
3.The Application of Digital Intelligence Technology in the Management of Non-Hospitalized Patients with Rare Diseases
Yiyang YAO ; Yi GAO ; Yixuan GUO ; Zhuoyue QIN ; Yaofang ZHANG ; Jiaqi JING ; Jing XIE ; Jian GUO ; Shuyang ZHANG
JOURNAL OF RARE DISEASES 2025;4(1):46-53
To provide references to and give suggestions to the development and optimiza-tion of Digital Intelligence (DI) technology in management of non-hospitalized patients by systematical review the application of digital technology in non-hospital settings. We designed the search strategy and used the words " rare diseases"" patient management"" non-hospitalized management"" community management"" digital intelligence"" big data"" telemedicine" as MESH terms or free words. We searched the database of PubMed, Science-Direct, Web of Science, CNKI, Wanfang and VIP from the beginning of the database to July 2024 and used computer retrieval to get the literatures on the application of DI technology in the management of patients with rare diseases in non-hospital setting. We extracted the information of the first author, country or region, publication time, research participants, DI technology application, and application effect for summary analysis. A total of 13 articles were included in this study, which were from 8 countries or regions. We found that DI technologies used were in the following forms: Internet information platform, wearable devices, telemedicine management platform and electronic database. The DI technology was used by the patients with rare diseases, patient caregivers and professional medical staffs. The application of all the forms above in different populations had good effect. The Internet information platform helped patients and their caregivers learn more about the disease and improved their self-management ability. The wearable device helped monitor the health status of patients in real time and predict the risk of emergent events. The telemedicine management platform facilitated to optimize the allocation of medical resources and strengthen doctor-patient communication. The electronic health database promoted the interconnection of data inside and outside the hospital and improved the accuracy of decision-making through data sharing. The application of DI technology in the management of patients with rare diseases in non-hospitalized settings has shown positive results. In the future, it is necessary to correct the shortcomings and to deal with the challenges in terms of accuracy, readiness, applicability, and privacy protection. Besides, the DI can be integrated into the tri-level management system of patients known as the "patient-community-hospital". It is advisable to take the advantages of digital intelligence technology to improve the efficiency and quality of management of patients in non-hospitalized settings.
4.The Development and Application of Chatbots in Healthcare: From Traditional Methods to Large Language Models
Zixing WANG ; Le QI ; Xiaodan LIAN ; Ziheng ZHOU ; Aiwei MENG ; Xintong WU ; Xiaoyuan GAO ; Yujie YANG ; Yiyang LIU ; Wei ZHAO ; Xiaolin DIAO
Medical Journal of Peking Union Medical College Hospital 2025;16(5):1170-1178
With the rapid advancement of artificial intelligence technology, chatbots have shown great potential in the healthcare sector. From personalized health advice to chronic disease management and psychological support, chatbots have demonstrated significant advantages in improving the efficiency and quality of healthcare services. As the scope of their applications expands, the relationship between technological complexity and practical application scenarios has become increasingly intertwined, necessitating a more comprehensive evaluation of both aspects. This paper, from the perspective of he althcare applications, systematically reviews the technological pathways and development of chatbots in the medical field, providing an in-depth analysis of their performance across various medical scenarios. It thoroughly examines the advantages and limitations of chatbots, aiming to offer theoretical support for future research and propose feasible recommendations for the broader adoption of chatbot technologies in healthcare.
5.Molecular Mechanisms of Huangjing Zanyu Capsule in Treating Oligoasthenospermia:A Study Based on AMPK-Mediated Mitophagy
Yuan GAO ; Yiyang GUO ; Mohan WU ; Yanfei ZHENG
Journal of Sichuan University (Medical Sciences) 2025;56(1):74-82
Objective To investigate the molecular mechanism of Huangjing Zanyu Capsule(HJZY),a new class-Ⅲ traditional Chinese medicine for the treatment of male infertility developed by Wang Qi,an academician of the Chinese Academy of Engineering,based on AMPK-mediated mitophagy in the treatment of oligoasthenospermia.Methods Acrolein(ACR)was used to treat GC-2spd(ts)mouse spermatocytes to establish a cell model of oligoasthenospermia.The optimal ACR concentration and exposure time for subsequent modeling were determined by CCK8 cell viability assay.After successful modeling,the cells were cultured in complete medium containing different concentrations of HJZY.Then,cell viability was assessed by CCK8 assay after 24 hours,and the subsequent treatment concentration was determined based on the cell viability.After the GC-2spd cells adhered to the wall,they were divided into a normal control(NC)group,a modeling group,and an ACR+HJZY treatment group.The effect of HJZY on mitophagy was observed by confocal fluorescence microscopy.The three groups of cells were transfected with siRNA-NC and siRNA-AMPK,respectively,and divided into six groups,including siRNA-NC+control,siRNA-NC+ACR,siRNA-NC+ACR+HJZY,siRNA-AMPK+control,siRNA-AMPK+ACR,and siRNA-AMPK+ACR+HJZY groups.Western blot was performed to validate the regulatory effect of HJZY on mitophagy-related proteins,such as p-AMPK,LC3B,P62,PINK1,Parkin,TBK1,and ULK1,which were all proteins mediated by AMPK.Results Through the cell viability assay,34 μmol/L was selected as the the modeling concentration of ACR,and 20 minutes was selected as the modeling time The treatment concentration of HJZY was 160 μmol/L.Confocal fluorescence microscopy showed that HJZY had,to a certain degree,a positive regulatory effect on the mitochondrial membrane potential of damaged spermatogenic cells.The mitochondrial membrane potential of the model group decreased significantly compared with that of the NC group.After exposure to treatment,the cell membrane potential of the ACR+HJZY treatment group increased compared with that of the model group,and the difference was statistically significant(P<0.05).Western blot results showed that the expression levels of p-AMPK/AMPK and PINK1 proteins in the siRNA-NC+ACR group were significantly lower than those in the siRNA-NC+control group(P<0.001).The level of Parkin protein in the siRNA-NC+ACR group was lower than that in the siRNA-NC+control group,but the difference was not statistically significant.After the administration of HJZY,the levels of these 3 proteins increased,and those in the siRNA-NC+ACR+HJZY group were higher than those in the siRNA-NC+ACR group(P<0.001).The expression levels of LC3B,P62,TBK1,and ULK1 proteins in the siRNA-NC+ACR group were higher than those in the siRNA-NC+control group(P<0.01),and those in the siRNA-NC+ACR+HJZY group were lower than those in the siRNA-NC+ACR group(P<0.05).After transfection with the gene-silencing siRNA-AMPK,the expression levels of p-AMPK/AMPK,PINK1,and Parkin proteins in the siRNA-AMPK+ACR group were lower than those in the siRNA-AMPK+control group(P<0.01).After the administration of HJZY,there was no significant difference in the levels of these three proteins between the siRNA-AMPK+ACR+HJZY group and the siRNA-AMPK+ACR group.The expression level of LC3B protein in the siRNA-AMPK+ACR+HJZY group was still lower than that in the siRNA-AMPK+ACR group(P<0.01).There was no significant difference in the levels of P62,TBK1,and ULK1 proteins between the siRNA-AMPK+ACR+HJZY group and the siRNA-AMPK+ACR group.Compared with the siRNA-NC+control group,the siRNA-AMPK+control group showed significantly decreased expression levels of p-AMPK/AMPK,ULK1,and TBK1 proteins(P<0.001),decreased expression of PINK1 protein(P<0.05),and increased expression of P62 protein(P<0.001).Compared with the siRNA-NC+ACR group,the siRNA-AMPK+ACR group showed decreased expression of TBK1 protein(P<0.001),decreased expression of LC3B protein(P<0.01),and decreased expression of ULK1 protein(P<0.05).The expression levels of PINK1 and Parkin proteins in the siRNA-AMPK+ACR group were lower than those in the siRNA-NC+ACR group,but the difference was not statistically significant.Compared with the siRNA-NC+ACR+HJZY group,the siRNA-AMPK+ACR+HJZY group showed decreased expression of p-AMPK/AMPK,PINK1,and Parkin proteins(P<0.05),decreased expression of LC3B protein(P<0.01),and increased expression of P62 protein(P<0.001).There was no significant difference in the levels of TBK1 and ULK1 proteins between the siRNA-AMPK+ACR+HJZY group and the siRNA-NC+ACR+HJZY group.Conclusion HJZY may exert its therapeutic effect on oligoasthenospermia by regulating AMPK-mediated mitophagy.
6.CT radiomics combined with CT and preoperative pathological features for predicting postoperative early recurrence of local advanced esophageal squamous cell carcinoma
Jingjing XING ; Yiyang LIU ; Yue ZHOU ; Pengchao ZHAN ; Rui WANG ; Yaru CHAI ; Peijie LYU ; Jianbo GAO
Chinese Journal of Medical Imaging Technology 2024;40(6):863-868
Objective To investigate the value of CT radiomics combined with CT and preoperative pathological features for predicting postoperative early recurrence(ER)of local advanced esophageal squamous cell carcinoma(LAESCC).Methods Data of 334 patients with LAESCC were retrospectively analyzed.The patients were divided into training set(n=234)and verification set(n=100)at the ratio of 7:3 and were followed up to observe ER(recurrence within 12 months after surgery)or not.Univariate and multivariate logistic regression were used to analyze clinical,CT and preoperative pathological features of LAESCC in patients with or without ER in training set.The independent risk factors of ER were screened,and a CT-preoperative pathology model was constructed.Based on venous phase CT in training set,the radiomics features of lesions were extracted and screened to establish radiomics model,and finally a combined model was established based on radiomics model and the independent risk factors.Receiver operating characteristic(ROC)curves were drawn,and the area under the curve(AUC)was calculated to evaluate the diagnostic efficacy of each model.Results Among 334 cases,168 were found with but 166 without ER.In training set,117 cases were found with while the rest 117 without ER,while in verification set,51 were found with but 49 without ER.The length of lesions,cT stage and cN stage shown on CT and tumor differentiation degree displayed with preoperative pathology were all independent risk factors for ER of LAESCC(all P<0.05).The AUC of CT-preoperative pathology model in training set and validation set was 0.759 and 0.783,respectively.Ten best radiomics features of LAESCC were selected,and AUC of the established radiomics model in training set and validation set was 0.770 and 0.730,respectively.The AUC of combined model in training and validation set was 0.838 and 0.826,respectively.The AUC of CT radiomics combined with CT and preoperative pathological features in training set was higher than that of CT-preoperative pathologymodel and radiomics model(both P<0.01).Conclusion CT radiomics combined with CT and preoperative pathological features could effectively predict postoperative ER of LAESCC.
7.Dual-energy CT radiomics combined with clinical and CT features for predicting differentiation degree of gastric adenocarcinoma
Mengchen YUAN ; Yiyang LIU ; Hongliang LI ; Lin CHEN ; Bo DUAN ; Shuai ZHAO ; Yaru YOU ; Xingzhi CHEN ; Jianbo GAO
Chinese Journal of Medical Imaging Technology 2024;40(10):1542-1547
Objective To observe the value of dual-energy CT(DECT)radiomics combined with clinical and CT features for predicting differentiation degree of gastric adenocarcinoma(GAC).Methods Totally 254 patients with GAC were prospectively analyzed and divided into high-grade group(low differentiation GAC,n=88)and low-grade group(middle-high differentiation GAC,n=166)according to pathological results.The patients were also divided into training set(n=203,including 70 high-grade and 133 low-grade GAC)and verification set(n=51,including 18 high-grade and 33 low-grade GAC)at the ratio of 8∶2.Radiomics features were extracted and screened based on venous phase single-level(40,70,100 and 140 keV)DECT,and a multi-energy radiomics model was constructed to predict GAC classification.Univariate analysis and multivariate logistic regression were used to analyze clinical and CT features as well as DECT parameters in training set to construct a clinic-CT model.Then a combined model was constructed through combining clinic-CT model with radiomics model.The predictive efficacy of the models were evaluated,and the calibration degree of the combined model was assessed.Results The area under the curve(AUC)of clinic-CT model,multi-energy radiomics model and combined model was 0.74,0.75 and 0.78 in training set,and 0.73,0.77 and 0.78 in verification set,respectively.Except for AUC of combined model was higher than that of clinic-CT model in training set(P<0.05),no significant difference of AUC was found among models in training set nor verification set(all P>0.05).The calibration degree of combined model was good in both training set and verification set(both P>0.05).Conclusion DECT radiomics combined with clinical and CT features could effectively predict differentiation degree of GAC.
8.Spectral CT quantitative parameters for evaluating T stage of advanced gastric cancer
Yaru YOU ; Yiyang LIU ; Mengchen YUAN ; Shuai ZHAO ; Liming LI ; Yusong CHEN ; Yue ZHENG ; Jianbo GAO
Chinese Journal of Medical Imaging Technology 2024;40(11):1704-1709
Objective To observe the value of spectral CT parameters for evaluating T staging of advanced gastric cancer(AGC).Methods Totally 155 AGC patients were collected and divided into T2 stage(n=40)and T3/4a stage(n=115)according to postoperative pathology.CT values,water concentration(WC)and iodine concentration(IC)of AGC lesions on 40-140 keV arteriovenous phase single energy level images were measured,and the standardized IC(nIC)and spectral curve slopes k1 and k2 were calculated.Clinical variables and spectral quantitative parameters were compared between groups,and receiver operating characteristic curve was plotted,the area under the curve(AUC)was calculated to evaluate the value of each parameter and model for identifying T2 and T3/4a stage AGC.Results Tumor thickness,proportion of low differentiation degree,CT100kev,CT140kev,and WC values in T3/4a group were all significantly higher than those in T2 group(all P<0.05).CT140keV of AGC lesions on venous phase images presented the highest discrimination efficacy among single parameters,with AUC of 0.782.AUC of clinical-arterial phase-venous phase model was 0.848,higher than that of clinical model and arterial phase model alone(both P<0.05)but not significantly different compared with AUC of venous phase model(P>0.05).Conclusion Spectral CT quantitative parameters,especially venous phase parameters could be used to effectively identify T stage of AGC.Multi-parameter combined models had higher diagnostic value.
9.Comparative study of low-keV deep learning reconstructed images and conventional images of gastric cancer based on dual-energy CT
Mengchen YUAN ; Yiyang LIU ; Hejun LIANG ; Lin CHEN ; Shuai ZHAO ; Yaru YOU ; Jianbo GAO
Chinese Journal of Radiology 2024;58(8):836-842
Objective:To assess the quality of low-keV monoenergetic images using deep learning image reconstruction (DLIR) algorithm combined with dual energy CT (DECT) in gastric cancer and to compare them with images from the conventional adaptive statistical iterative reconstruction (ASiR-V) algorithm.Methods:In this cross-sectional study, DECT images of 31 gastric cancer patients in the First Affiliated Hospital of Zhengzhou University were prospectively collected from September 2022 to March 2023. The 55 keV monoenergy images were reconstructed using the DLIR algorithm at low-, medium-, and high-intensity levels (DLIR-L, DLIR-M, and DLIR-H) based on arterial phase and venous phase images, respectively. The 70 keV 40% mixing coefficient (ASiR-V40%) images were reconstructed using the ASiR-V algorithm. In the objective evaluation of images, the signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) for both lesions and muscle were calculated across four sets of reconstructed images. In the subjective evaluation of images, scores were assigned to the overall image quality, lesion visibility, and diagnostic confidence for each set of reconstructed images. Comparisons of SNR and CNR between the 4 groups were made by One-way repeated-measures ANOVA or Friedman′s test. Comparisons of scores were made by Friedman′s test. The P value of pairwise comparison was adjusted using Bonferroni correction methods. Results:In the objective evaluations, CNR lesion, SNR lesion and SNR muscle were highest on the 55 keV DLIR-H images in the arterial and venous phases, and showed a gradually increasing trend on the 70 keV ASiR-V40%, 55 keV DLIR-L, DLIR-M, DLIR-H images ( P<0.05). In subjective evaluations, compared to the 70 keV ASiR-V40% images, overall image quality scores were numerically higher for the 55 keV DLIR-H ( P>0.05), similar or slightly worse for the 55 keV DLIR-M, and significantly lower for the 55 keV DLIR-L ( P<0.05). The lesion visibility and diagnostic confidence on the 55 keV DLIR reconstruction images were higher in both arterial and venous phases than 70 keV ASiR-V40% images ( P<0.05). Conclusions:Compared to the conventional 70 keV ASiR-V40% images, the 55 keV DLIR-H images had higher lesion contrast and diagnostic confidence with lower image noise. The 55 keV DLIR-M images had comparable overall image quality to 70 keV ASiR-V40% images, but the former had higher lesion contrast and diagnostic confidence. The 55 keV DLIR-L was unable to improve image quality to the level of 70 keV ASiR-V40%.
10.Discussion on the Application Prospects and Challenges of Generative Artificial Intelligence Represented by ChatGPT in the Field of Hospital Management
Mingwang FANG ; Ling GUO ; Yingde HUANG ; Wei YUAN ; Yunyi GAO ; Yi ZHOU ; Yiyang ZHAO ; Bingxing SHUAI ; Xiangjun CHEN ; Weiyi ZHANG ; Dajiang LI
Journal of Medical Informatics 2024;45(10):18-21
Purpose/Significance To explore the changes,challenges,key application scenarios and future development directions of generative artificial intelligence(AI)represented by ChatGPT in the field of hospital management,and to provide references for the ap-plication of AI natural language processing(NLP)technology in the field of hospital management in China.Method/Process Through literature review and analysis,the changes and challenges brought about by the rapid development of generative AI in the field of hospital management are sorted out,its key application scenarios and future development directions in the field of hospital management are empha-sized and explored.Result/Conclusion AI has broad application prospects in the field of hospital management,and it should focus on exploring its practical application scenarios and strategic directions to provide reference and guidance for promoting the high-quality de-velopment of public hospitals.

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