1.Deubiquitinase JOSD2 alleviates colitis by inhibiting inflammation via deubiquitination of IMPDH2 in macrophages.
Xin LIU ; Yi FANG ; Mincong HUANG ; Shiliang TU ; Boan ZHENG ; Hang YUAN ; Peng YU ; Mengyao LAN ; Wu LUO ; Yongqiang ZHOU ; Guorong CHEN ; Zhe SHEN ; Yi WANG ; Guang LIANG
Acta Pharmaceutica Sinica B 2025;15(2):1039-1055
Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract, which increases the incidence of colorectal cancer (CRC). In the pathophysiology of IBD, ubiquitination/deubiquitination plays a critical regulatory function. Josephin domain containing 2 (JOSD2), a deubiquitinating enzyme, controls cell proliferation and carcinogenesis. However, its role in IBD remains unknown. Colitis mice model developed by dextran sodium sulfate (DSS) or colon tissues from individuals with ulcerative colitis and Crohn's disease showed a significant upregulation of JOSD2 expression in the macrophages. JOSD2 deficiency exacerbated the phenotypes of DSS-induced colitis by enhancing colon inflammation. DSS-challenged mice with myeloid-specific JOSD2 deletion developed severe colitis after bone marrow transplantation. Mechanistically, JOSD2 binds to the C-terminal of inosine-5'-monophosphate dehydrogenase 2 (IMPDH2) and preferentially cleaves K63-linked polyubiquitin chains at the K134 site, suppressing IMPDH2 activity and preventing activation of nuclear factor kappa B (NF-κB) and inflammation in macrophages. It was also shown that JOSD2 knockout significantly exacerbated increased azoxymethane (AOM)/DSS-induced CRC, and AAV6-mediated JOSD2 overexpression in macrophages prevented the development of colitis in mice. These outcomes reveal a novel role for JOSD2 in colitis through deubiquitinating IMPDH2, suggesting that targeting JOSD2 is a potential strategy for treating IBD.
2.Sex Differences of White Matter Damage in Alzheimer's Disease and Its Association with Cognitive Impairment
Yun LU ; Xiaoshu LI ; Wanqiu ZHU ; Ziwen GAO ; Yuqing LI ; Wenrui WANG ; Wei YE ; Xiao CHEN ; Ju MA ; Yongqiang YU
Chinese Journal of Medical Imaging 2025;33(6):618-626
Purpose To investigate the sex differences of white matter damage in Alzheimer's disease(AD)and their association with cognitive impairment.Materials and Methods This retrospective study included 88 AD patients(48 females),71 amnestic mild cognitive impairment(aMCI)patients(39 females),and 95 healthy controls(63 females)recruited from the Memory Disorder Clinic at the First Affiliated Hospital of Anhui Medical University from September 2017 to July 2024.High-resolution three-dimensional T1 structure images and diffusion tensor imaging images were all obtained from each participant.The mean diffusivity(MD)and fractional anisotropy(FA)values of each white matter region were obtained,and the two-way ANOVA analysis was conducted to investigate brain regions with interaction effects between groups and sexes,those brain regions were then chosen as regions of interest for further correlation analysis with a series of cognitive scale scores.Results In terms of FA values,the right posterior corona radiata,right anterior limb of the internal capsule and left corticospinal tract showed interaction between sexes and cognitive groups(F=4.764,3.812,5.937,all P<0.05).The FA value of AD group was significantly lower than that of healthy control and aMCI group(all P<0.05),but there was no significant difference between healthy control and aMCI group(except the right anterior limb of the internal capsule,P=0.018).In AD group,FA values were significantly higher in women than in men in the previously described brain regions(all P<0.05),while there was no significant difference in FA values between male and female in healthy control and aMCI groups(except the left corticospinal tract,P<0.001).In terms of MD values,the right anterior limb of the internal capsule,right superior corona radiata and left external capsule showed interaction effect between sexes and cognitive groups(F=8.581,3.680,7.218,all P<0.05).The MD value of AD group was significantly higher than that of aMCI group(P<0.001),and aMCI group was higher than that of healthy control group(all P<0.05).In AD group,the MD values in the above brain regions were significantly higher in males than those in females(all P<0.01),while no significant difference was found between males and females in healthy control and aMCI groups(except for the left external capsule,P<0.05).For correlation analysis,the AD group was dimidiated into two groups by sex,the scores of the Montreal cognitive assessment,the Mini Mental state examination and the verbal fluency test of the female patient group were positively correlated with the FA values of the right posterior corona radiate(r=0.372,P=0.009;r=0.345,P=0.016;r=0.383,P=0.007),while the Mini Mental state examination and the verbal fluency test scores of female AD patient group were negatively correlated with the MD values of the right superior corona radiata(r=-0.360,P=0.012;r=-0.360,P=0.003).Conclusion Compared to the healthy control and MCI groups,white matter damage in AD patients shows sex differences and is associated with general cognitive and language functions impairment in female AD patients.
3.Diagnostic value of amide proton imaging for clinically significant prostate cancer in prostate imaging reporing and data system 3-5 grade lesions
Hongkun FANG ; Shuhai ZHANG ; Shoubin LI ; Xiaoqin LIU ; Yongqiang YU ; Weishu HOU
Journal of Practical Radiology 2025;41(5):795-800
Objective To explore the diagnostic value of amide proton transfer weighted imaging(APTWI)in conjunction with prostate-specific antigen density(PSAD)for detecting clinically significant prostate cancer(csPCa)within prostate imaging reporting and data system(PI-RADS)v2.13-5 grade lesions.Methods A retrospective analysis was conducted on the clinical and imaging data of 88 patients diagnosed with PI-RADS 3-5 grade prostate lesions.There were 59 patients with prostate cancer(PCa)and 29 with benign prostate lesion(BPL).The PCa group was divided into csPCa group(44 cases)and clinically insignificant prostate cancer(ciPCa)group(15 cases)according to Gleason score(GS).Spearman rank correlation analysis was used to analyze the correlation between APTWI-related parameters and GS in PCa.Comparative analyses were conducted to identify statistical discrepancies in APTWI and prostate-specific antigen(PSA)-related parameters across various groups.Subsequently,both solitary and combined diagnostic models were developed,and the receiver operating characteristic(ROC)curve were utilized to evaluate the diagnostic efficacy.Results APTmax and APTmean were moderately positively correlated with GS(r=0.683,r=0.705,respectively),and APTmin was weakly positively correlated with GS(r=0.547).APTWI and PSA-related parameters were significantly higher in the PCa group than in the BPL group,and APTmin had the highest efficacy in diagnosing PCa[area under the curve(AUC)=0.855].APTWI and PSA-related parameters differed among the BPL,ciPCa and csPCa groups(P<0.05).Among the groups,statistically significant differences were observed in each parameter of APTWI and PSA-related indices between the BPL group and the csPCa group,as well as between the ciPCa group and the csPCa group(P<0.05).In contrast,only APTmin and PSAD exhibited significant differ-ences between the BPL group and the ciPCa group(P<0.05).The results of the combined diagnosis showed that APTmin+PSAD had the highest diagnostic efficacy for diagnosing PCa(AUC=0.899),and APTmean+PSAD had the highest diagnostic efficacy for diagnosing csPCa(AUC=0.838).Conclusion In PI-RADS 3-5 grade prostate lesions,APTWI and PSA-related parameters are statisti-cally different in the BPL,ciPCa,and csPCa groups.Notably,the combination of APTmean and PSAD exhibit the highest diagnostic efficacy for csPCa.
4.A clinical study of deep learning image reconstruction algorithms in liver dual-energy CT with reduced radiation dose to further improve image quality and lesion diagnostic confidence
Yuncheng LI ; Yuguo LI ; Junlin YANG ; Jian SONG ; Xing TANG ; Wei DENG ; Zhen WANG ; Jinxiu YANG ; Bin LIU ; Yongqiang YU ; Xiaohu LI
Chinese Journal of Radiology 2025;59(1):43-49
Objective:To explore the feasibility of applying deep learning image reconstruction (DLIR) in low-radiation dose liver dual-energy CT to further improve image quality, diagnostic confidence of lesion, and accuracy of iodine concentration (IC) measurement.Methods:This prospective cohort study enrolled 60 patients scheduled for enhanced liver CT at the First Affiliated Hospital of Anhui Medical University from June 2023 to January 2024. The participants were randomly assigned into the standard dose group and low radiation dose group with 30 cases in each using randomized block method. The standard radiation dose group underwent standard-radiation dose 120 kVp scans during the venous phase, while the low radiation dose group underwent low radiation dose scans with a rapid kVp-switching spectral scanning mode at 80 kVp and 140 kVp. The effective radiation dose (ED) was calculated for both groups. The standard radiation dose group was reconstructed using adaptive statistical iterative reconstruction-V (ASIR-V) algorithm 40% (AR40 120 kVp). The low radiation dose group using high-intensity DLIR (DLIR-H) to reconstructed 40 keV and 50 keV virtual monoenergetic images (VMI) (DH-VMI 40 keV, DH-VMI 50 keV). The image quality of the above three groups was objectively evaluated through the measurement of image noise and calculation of contrast-to-noise ratio (CNR) and signal-to-noise ratio (SNR) for the liver and portal vein; and the image quality was subjectively scored for image noise, contrast, lesion conspicuity, and diagnostic confidence. In the low radiation dose group, DLIR-H and ASIR-V40% reconstructed iodine maps were used to measure the liver and portal vein of IC values, standard deviations (SD), and coefficients of variation (CV). One-way analysis of variance or Kruskal-Wallis H test was used to compare the differences of subjective and objective image quality among the three groups, and paired t-test was used to compare the differences in measurement indexes between DLIR-H and ASIR-V40% reconstructed iodine maps. Results:The ED in the low radiation dose group [(2.2±0.5) mSv] was reduced by 56.8% compared to the conventional radiation dose group [(5.4±1.4) mSv]. Objective evaluations demonstrated that DH-VMI 40 keV had higher image noise, CNR, and SNR for liver and portal veins compared to AR40 120 kVp ( P<0.001). DH-VMI 50 keV had lower image noise ( P=0.200), with higher CNR and SNR for the liver and portal vein compared to AR40 120 kVp( P<0.001). In subjective evaluation, there was no statistically significant difference in image noise scores between DH-VMI 40 keV and AR40 120 kVp ( P>0.05), while the image noise score for DH-VMI 50 keV was lower than that of AR40 120 kVp ( P<0.05). Both DH-VMI 40 keV and DH-VMI 50 keV had higher scores for contrast, lesion conspicuity, and diagnostic confidence compared to those of AR40 120 kVp ( P<0.05). In the low radiation dose group, there was no statistically significant difference in IC values for the liver and portal vein between the ASIR-V40% and DLIR-H algorithm reconstructed iodine maps ( P>0.05). The SD and CV of liver and portal vein in the DLIR-H reconstructed iodine maps were lower than those in the ASIR-V40% reconstructed iodine maps ( P<0.001). Conclusions:DLIR can effectively reduce the image noise of low-energy (40, 50 keV) VMI, enhance lesion conspicuity and diagnostic confidence, and improve measurement accuracy without affecting IC values.
5.Mechanism of action of bile-gut axis in the development and progression of intrahepatic cholangiocarcinoma
Xue YU ; Tianhao SHEN ; Cheng ZHOU ; Yu LIU ; Wei LI ; Tinghui JIANG ; Yongqiang ZHU ; Yan LIU
Journal of Clinical Hepatology 2025;41(3):588-593
Intrahepatic cholangiocarcinoma is a malignant tumor with an extremely poor prognosis, and its pathogenesis is complex and remains unclear. In recent years, more and more studies have focused on the role of bile-gut axis in the development and progression of intrahepatic cholangiocarcinoma. Bile-gut axis refers to the complex interaction between bile and gut microbiota, including bile salt metabolism, dynamic changes of microbiota, inflammatory response, and immune system regulation. This article elaborates on the potential mechanisms of bile-gut axis in intrahepatic cholangiocarcinoma, especially gut microbiota dysbiosis, abnormal bile salt metabolism, chronic inflammatory response, and immune system interaction, this article aims to provide new perspectives and possible therapeutic targets for future research and promote the early diagnosis and effective treatment of intrahepatic cholangiocarcinoma.
6.The Effect of Fuzheng Huaji Formula (扶正化积方) for Chronic Hepatitis B on Reduction of the Incidence of Liver Cirrhosis and Hepatocellular Carcinoma:A Retrospective Cohort Study
Simiao YU ; Jiahui LI ; Jing JING ; Tingting HE ; Yongqiang SUN ; Liping WANG ; Aozhe ZHANG ; Xiaohe XIAO ; Xia DING ; Ruilin WANG
Journal of Traditional Chinese Medicine 2025;66(3):268-274
ObjectiveTo evaluate the clinical efficacy of Fuzheng Huaji Formula (扶正化积方) for chronic hepatitis B to reduce the incidence of liver cirrhosis and hepatocellular carcinoma. MethodsA retrospective cohort study was conducted, collecting medical records of 118 patients with chronic hepatitis B and 234 patients with hepatitis B-related cirrhosis who visited the hospital between January 1, 2014, and December 31, 2018. The use of Fuzheng Huaji Formula was designated as the exposure factor. Patients receiving antiviral treatment for hepatitis B without concurrent Fuzheng Huaji Formula therapy were included in the western medicine group, while those receiving antiviral treatment combined with Fuzheng Huaji Formula for a cumulative treatment lasting longer than 3 months were included in the combined treatment group. The follow-up observation period was five years. Kaplan-Meier survival analysis was used to assess the cumulative incidence of cirrhosis in patients with chronic hepatitis B and the cumulative incidence of hepatocellular carcinoma in patients with hepatitis B-related cirrhosis. Univariate and multivariate Cox regression analyses were employed to examine the factors influencing the occurrence of cirrhosis and hepatocellular carcinoma. ResultsAmong patients with chronic hepatitis B, there were 55 cases in the combined treatment group and 63 cases in the western medicine group; among patients with hepatitis B-related cirrhosis, there were 110 cases in the combined treatment group and 124 cases in the western medicine group. Five-year follow-up outcomes for chronic hepatitis B patients showed that the cumulative incidence of cirrhosis was 5.45% (3/55) in the combined treatment group and 17.46% (11/63) in the western medicine group, with a statistically significant difference between groups (Z = 2.003, P = 0.045). Five-year follow-up outcomes for hepatitis B-related cirrhosis patients showed that the cumulative incidence of hepatocellular carcinoma was 8.18% (9/110) in the combined treatment group and 22.58% (28/124) in the western medicine group, also showing a statistically significant difference (Z = 3.007, P = 0.003). Univariate and multivariate Cox regression analyses indicated that treatment with Fuzheng Huaji Formula is an independent protective factor in preventing the progression of chronic hepatitis B to cirrhosis and the progression of hepatitis B-related cirrhosis to hepatocellular carcinoma (P<0.05). ConclusionCombining Fuzheng Huaji Formula with antiviral therapy for hepatitis B can effectively intervene in the disease progression of chronic hepatitis B, reducing the incidence of cirrhosis and hepatocellular carcinoma.
7.Research advances in traditional Chinese medicine for the prevention and treatment of inflammation-to-cancer transformation in chronic hepatitis
Simiao YU ; Sici WANG ; Haocheng ZHENG ; Yongqiang SUN ; Jing JING ; Tingting HE ; Liping WANG ; Aozhe ZHANG ; Xin WANG ; Xia DING ; Ruilin WANG
Journal of Clinical Hepatology 2025;41(9):1888-1895
Primary liver cancer is one of the most common malignant tumors of the digestive system, and the “inflammation-to-cancer transformation” (ICT) of chronic hepatitis is the core pathological process of the progression of chronic hepatitis to liver cancer. Persistent and uncontrolled liver inflammation in patients with chronic hepatitis often leads to repeated liver tissue damage and repair, which gradually develops into liver fibrosis and cirrhosis, eventually leading to malignant transformation through the mechanisms such as gene mutation and microenvironment imbalance. ICT in chronic hepatitis is the key link between chronic hepatitis and liver cancer, and its dynamic evolution involves various pathogenic factors such as dampness, heat, deficiency, toxin, and stasis; among which damp-heat and vital energy deficiency are the initiating factors for ICT of chronic hepatitis, while intermingled stasis and toxin are the key pathological products that promote malignant transformation. Based on the concept of preventive treatment, traditional Chinese medicine can effectively delay and even block the ICT of chronic hepatitis by regulating inflammation, metabolism, and abnormal cell proliferation through multiple targets, which provides important strategies and research directions for the prevention and treatment of liver cancer.
8.Nomogram based on DCE-MRI radiomics combined with clinical-radiological features in predicting hormone receptor status in breast cancer with low Her-2 expression
Weishu Hou ; Hongli Pan ; Qun Wang ; Xiaohu Li ; Yunwen Yan ; Yongqiang Yu
Acta Universitatis Medicinalis Anhui 2025;60(9):1745-1754
Objective:
To explore the value of nomogram based on DCE-MRI radiomics combined with clinical-ra- diological features in predicting HR status in breast cancer with Her-2 low expression.
Methods:
A total of 198 pa- tients of Her-2 low expression breast cancer who underwent standardized breast MRI in our hospital from January 2019 to February 2025 were retrospectively analyzed.Patients were divided into HR ( + ) group ( n = 137) and HR ( -) group ( n = 61) .The cases were divided into a training set ( 138 cases) and a testing set ( 60 cases) in a 7 ∶ 3 ratio.Clinical-radiological model was based on clinical and traditional radiological features,radiomics model was based on DCE-MRI,and combined model was constructed,respectively.The nomogram was drawn,and re- ceiver operating characteristic curve was used to compare the performance of different models in predicting HR sta- tus.
Results:
The DCE-MRI radiomics score ( Radscore) between the HR ( + ) group and the HR ( -) group showed statistical differences in both the training and testing sets ( both P<0. 001) .The AUC of the clinical-radio- logical model based on lesion mobility,Ki67,TIC type,enhancement pattern and maximum diameter for predicting HR status in the training set and testing set were 0. 643 and 0. 616,respectively.The AUC of the DEC-MRI ra- diomics model in the training set and testing set were 0. 897 and 0. 860,respectively.The nomogram drawn by combining clinical-radiological features and Radscore showed better predictive performance in both the training set ( AUC = 0. 913) and testing set ( AUC = 0. 898) than the clinical-radiological model ( all P<0. 05) .
Conclusion
The nomogram combined by DCE-MRI radiomics and clinical-radiological features can effectively predict HR sta-tus of breast cancer with low Her-2 expression,which is helpful to the building of individualized treatment plan for breast cancer patients.
9.Resting-state functional MRI fractional amplitude of low-frequency fluctuation for evaluating white matter function in adolescent smokers
Daining SONG ; Ting XUE ; Dahua YU ; Junxuan WANG ; Wuyuan XIN ; Jingjing DING ; Lin LUO ; Yongqiang KANG
Chinese Journal of Medical Imaging Technology 2025;41(3):473-476
Objective To observe changes of white matter function in adolescent smoker(AS)with resting-state functional MRI(rs-fMRI)fractional amplitude of low-frequency fluctuation(fALFF)technique.Methods Forty-five adolescents(AS group)and 45 control subjects(control group)were prospectively enrolled,and brain rs-fMRI were acquired.Brain regions with fALFF being different between groups were observed,and the correlations with clinical indicators were analyzed.Results Compared with that in control group,fALFF of the right superior longitudinal fasciculus significantly elevated in AS group(FDR correct Q<0.05),in which the peak of the cluster was positively correlated with score of Fagerstr?m test for nicotine dependence(FTND)(r=0.294,P=0.049).Conclusion White matter function changed in AS,presenting as significantly increased fALFF in right superior longitudinal fasciculus,which was positively correlated with nicotine dependence.
10.Diagnostic value of amide proton imaging for clinically significant prostate cancer in prostate imaging reporing and data system 3-5 grade lesions
Hongkun FANG ; Shuhai ZHANG ; Shoubin LI ; Xiaoqin LIU ; Yongqiang YU ; Weishu HOU
Journal of Practical Radiology 2025;41(5):795-800
Objective To explore the diagnostic value of amide proton transfer weighted imaging(APTWI)in conjunction with prostate-specific antigen density(PSAD)for detecting clinically significant prostate cancer(csPCa)within prostate imaging reporting and data system(PI-RADS)v2.13-5 grade lesions.Methods A retrospective analysis was conducted on the clinical and imaging data of 88 patients diagnosed with PI-RADS 3-5 grade prostate lesions.There were 59 patients with prostate cancer(PCa)and 29 with benign prostate lesion(BPL).The PCa group was divided into csPCa group(44 cases)and clinically insignificant prostate cancer(ciPCa)group(15 cases)according to Gleason score(GS).Spearman rank correlation analysis was used to analyze the correlation between APTWI-related parameters and GS in PCa.Comparative analyses were conducted to identify statistical discrepancies in APTWI and prostate-specific antigen(PSA)-related parameters across various groups.Subsequently,both solitary and combined diagnostic models were developed,and the receiver operating characteristic(ROC)curve were utilized to evaluate the diagnostic efficacy.Results APTmax and APTmean were moderately positively correlated with GS(r=0.683,r=0.705,respectively),and APTmin was weakly positively correlated with GS(r=0.547).APTWI and PSA-related parameters were significantly higher in the PCa group than in the BPL group,and APTmin had the highest efficacy in diagnosing PCa[area under the curve(AUC)=0.855].APTWI and PSA-related parameters differed among the BPL,ciPCa and csPCa groups(P<0.05).Among the groups,statistically significant differences were observed in each parameter of APTWI and PSA-related indices between the BPL group and the csPCa group,as well as between the ciPCa group and the csPCa group(P<0.05).In contrast,only APTmin and PSAD exhibited significant differ-ences between the BPL group and the ciPCa group(P<0.05).The results of the combined diagnosis showed that APTmin+PSAD had the highest diagnostic efficacy for diagnosing PCa(AUC=0.899),and APTmean+PSAD had the highest diagnostic efficacy for diagnosing csPCa(AUC=0.838).Conclusion In PI-RADS 3-5 grade prostate lesions,APTWI and PSA-related parameters are statisti-cally different in the BPL,ciPCa,and csPCa groups.Notably,the combination of APTmean and PSAD exhibit the highest diagnostic efficacy for csPCa.


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