1.Cyclization diversity of meroditerpenoids from endophytic fungi of medicinal plants driven by synthetic biology strategies
Yuntao JIANG ; Zonghua XIAO ; Lianqiong DU ; Yukai SUO ; Xuping ZHANG ; Weiguang WANG
Science of Traditional Chinese Medicine 2025;3(1):81-86
Background: Medicinal plants rich in endophytic fungi are a significant source of natural lead compounds. Meroterpenoids, which are hybrid natural products originating from partially terpenoid pathways, exhibit impressive structural complexity and substantial potential as drug candidates. The structural diversity of meroterpenoids is largely attributed to the functional diversity of terpenoid cyclases, which generate a variety of terpenoid compounds with different ring systems. This enzymatic versatility underscores the biochemical potential of endophytic fungi and their invaluable role in drug discovery. Objective: The aim of the study was to investigate the role of endophytic fungi from Paris polyphylla var. yunnanensis in facilitating diverse cyclization modifications of meroditerpenoids through four terpene cyclases (TCs) from the Pyr4 family. Methods: This study utilized a recombinant strategy to successfully reconstruct four distinct TCs from endophytic fungi in the heterologous host, Aspergillus oryzae NSAR1. The structural characterization of the resulting secondary metabolites was performed using mass spectrometry and NMR techniques. Results: The substitution of TCs from the endophytes Aspergillus felis 0260 and Fusarium graminearum 1962 in Aspergillus oryzae through hydrophobic intermediates 1 and 2, led to the production of meroditerpenoids sartorypyrone C (3) and a new compound, 4′-methylchevalone E (4), respectively. This study demonstrates the critical role of endophytic fungi in enhancing structural diversity. Conclusions: These findings provide valuable insights into the compatibility of pathway combinations and the interchangeability of terpene cyclases derived from endophytic fungi in medicinal plants, which advanced the understanding of meroditerpenoid biosynthesis and highlighted the importance of endophytic fungi in drug discovery.
2.Cyclization diversity of meroditerpenoids from endophytic fungi of medicinal plants driven by synthetic biology strategies
Yuntao JIANG ; Zonghua XIAO ; Lianqiong DU ; Yukai SUO ; Xuping ZHANG ; Weiguang WANG
Science of Traditional Chinese Medicine 2025;3(1):81-86
Background: Medicinal plants rich in endophytic fungi are a significant source of natural lead compounds. Meroterpenoids, which are hybrid natural products originating from partially terpenoid pathways, exhibit impressive structural complexity and substantial potential as drug candidates. The structural diversity of meroterpenoids is largely attributed to the functional diversity of terpenoid cyclases, which generate a variety of terpenoid compounds with different ring systems. This enzymatic versatility underscores the biochemical potential of endophytic fungi and their invaluable role in drug discovery. Objective: The aim of the study was to investigate the role of endophytic fungi from Paris polyphylla var. yunnanensis in facilitating diverse cyclization modifications of meroditerpenoids through four terpene cyclases (TCs) from the Pyr4 family. Methods: This study utilized a recombinant strategy to successfully reconstruct four distinct TCs from endophytic fungi in the heterologous host, Aspergillus oryzae NSAR1. The structural characterization of the resulting secondary metabolites was performed using mass spectrometry and NMR techniques. Results: The substitution of TCs from the endophytes Aspergillus felis 0260 and Fusarium graminearum 1962 in Aspergillus oryzae through hydrophobic intermediates 1 and 2, led to the production of meroditerpenoids sartorypyrone C (3) and a new compound, 4′-methylchevalone E (4), respectively. This study demonstrates the critical role of endophytic fungi in enhancing structural diversity. Conclusions: These findings provide valuable insights into the compatibility of pathway combinations and the interchangeability of terpene cyclases derived from endophytic fungi in medicinal plants, which advanced the understanding of meroditerpenoid biosynthesis and highlighted the importance of endophytic fungi in drug discovery.
3.Cyclization diversity of meroditerpenoids from endophytic fungi of medicinal plants driven by synthetic biology strategies
Yuntao JIANG ; Zonghua XIAO ; Lianqiong DU ; Yukai SUO ; Xuping ZHANG ; Weiguang WANG
Science of Traditional Chinese Medicine 2025;3(1):81-86
Background: Medicinal plants rich in endophytic fungi are a significant source of natural lead compounds. Meroterpenoids, which are hybrid natural products originating from partially terpenoid pathways, exhibit impressive structural complexity and substantial potential as drug candidates. The structural diversity of meroterpenoids is largely attributed to the functional diversity of terpenoid cyclases, which generate a variety of terpenoid compounds with different ring systems. This enzymatic versatility underscores the biochemical potential of endophytic fungi and their invaluable role in drug discovery. Objective: The aim of the study was to investigate the role of endophytic fungi from Paris polyphylla var. yunnanensis in facilitating diverse cyclization modifications of meroditerpenoids through four terpene cyclases (TCs) from the Pyr4 family. Methods: This study utilized a recombinant strategy to successfully reconstruct four distinct TCs from endophytic fungi in the heterologous host, Aspergillus oryzae NSAR1. The structural characterization of the resulting secondary metabolites was performed using mass spectrometry and NMR techniques. Results: The substitution of TCs from the endophytes Aspergillus felis 0260 and Fusarium graminearum 1962 in Aspergillus oryzae through hydrophobic intermediates 1 and 2, led to the production of meroditerpenoids sartorypyrone C (3) and a new compound, 4′-methylchevalone E (4), respectively. This study demonstrates the critical role of endophytic fungi in enhancing structural diversity. Conclusions: These findings provide valuable insights into the compatibility of pathway combinations and the interchangeability of terpene cyclases derived from endophytic fungi in medicinal plants, which advanced the understanding of meroditerpenoid biosynthesis and highlighted the importance of endophytic fungi in drug discovery.
4.Effect of azvudine on prevention of SARS-CoV-2 infection among population of close contact with families with symptomatic SARS-CoV-2 infection
Chao JIANG ; Xuping DENG ; Hai FAN ; Peng JIANG
Chinese Journal of Nosocomiology 2025;35(18):2736-2740
OBJECTIVE T o explore the effectiveness and safety of azvudine in prevention of SARS-CoV-2 infection among the population of close contact with families with symptomatic SARS-CoV-2 infection.METHODS A total of 64 people who were closely contact with the families with symptomatic SARS-CoV-2 infection and were trea-ted in Ma'anshan People's Hospital from Jan.2023 to Oct.2023 were enrolled in the study and randomly divid-ed into the group A with 22 cases,the group B with 17 cases and the group C with 25 cases.The group A was giv-en 5mg of azvudine,the group B was given 3mg of azvudine plus 2mg of placebo,and the group C was given 5 mg of azvudine;all the three groups were treated for 7 days in total.The incidence of SARS-CoV-2 infection and the levels of interleukin-6(IL-6),C-reactive protein(CRP),immunoglobulin G(IgG)and immunoglobulin M(IgM)were observed among the three groups of research subjects after the drug therapies;the adverse reactions were re-corded during the research period.RESULTS The incidence rate of SARS-CoV-2 infection was 4.55%in the group A,11.76%in the group B,12.00%in the group C,and there was no significant difference(x2=0.921,P=0.631).There were no significant differences in the levels of IL-6,CRP,IgG and IgM among the three groups be-fore and after the drug therapies.The incidence of adverse reactions such as fatigue,cough,hypertriglyceridemia and gastrointestinal tract reactions was 9.09%in the group A after the drug therapies,11.76%in the group B,12.00%in the group C,and there was no significant difference.CONCLUSION There is no significant difference in the effectiveness of azvudine in prevention of SARS-CoV-2 infection among the population of close contact with families with symptomatic SARS-CoV-2 infection,with the safety and tolerance favorable.
5.Visual analysis of research hotspots in-hospital stroke from Chinese and English literature by CiteSpace
Nan YANG ; Guoyong ZENG ; Hong QIU ; Shuiying ZENG ; Jun LIU ; Qing HUANG ; Xuping JIANG
Chinese Journal of Modern Nursing 2025;31(5):616-622
Objective:To conduct a visual analysis of the research hotspots and development frontiers in-hospital stroke from both Chinese and English literature.Methods:Relevant literature on in-hospital stroke was retrieved from the Web of Science Core Collection, China National Knowledge Infrastructure, and Wanfang Database, with the search period extending from the inception of each database to June 2024. CiteSpace 6.2R3 was used to analyze the cooperation networks of authors, countries/regions, and institutions, and to conduct co-occurrence, clustering, and emerging keyword analyses.Results:A total of 465 English papers and 72 Chinese papers were included, showing a year-on-year increase in the overall number of publications. The research in English literature was concentrated in United States, with close cooperation between European and American countries, and comprehensive universities as the main research institutions. In Chinese literature, major research institutions were located in teaching hospitals, with limited collaboration between institutions. The research hotspots and frontiers can be categorized into three themes: risk factors, reperfusion therapy, and quality improvement.Conclusions:Research in in-hospital stroke in both Chinese and English literature is at a stable development stage, with both commonalities and differences in research directions. Future studies should focus on enhancing cooperation between authors, disciplines, institutions, and countries, further exploring the risk factors and mechanisms of in-hospital stroke, implementing precision treatment, building prevention and treatment systems, and expanding the breadth and depth of research in this field.
6.Real-world efficacy and safety of azvudine in hospitalized older patients with COVID-19 during the omicron wave in China: A retrospective cohort study.
Yuanchao ZHU ; Fei ZHAO ; Yubing ZHU ; Xingang LI ; Deshi DONG ; Bolin ZHU ; Jianchun LI ; Xin HU ; Zinan ZHAO ; Wenfeng XU ; Yang JV ; Dandan WANG ; Yingming ZHENG ; Yiwen DONG ; Lu LI ; Shilei YANG ; Zhiyuan TENG ; Ling LU ; Jingwei ZHU ; Linzhe DU ; Yunxin LIU ; Lechuan JIA ; Qiujv ZHANG ; Hui MA ; Ana ZHAO ; Hongliu JIANG ; Xin XU ; Jinli WANG ; Xuping QIAN ; Wei ZHANG ; Tingting ZHENG ; Chunxia YANG ; Xuguang CHEN ; Kun LIU ; Huanhuan JIANG ; Dongxiang QU ; Jia SONG ; Hua CHENG ; Wenfang SUN ; Hanqiu ZHAN ; Xiao LI ; Yafeng WANG ; Aixia WANG ; Li LIU ; Lihua YANG ; Nan ZHANG ; Shumin CHEN ; Jingjing MA ; Wei LIU ; Xiaoxiang DU ; Meiqin ZHENG ; Liyan WAN ; Guangqing DU ; Hangmei LIU ; Pengfei JIN
Acta Pharmaceutica Sinica B 2025;15(1):123-132
Debates persist regarding the efficacy and safety of azvudine, particularly its real-world outcomes. This study involved patients aged ≥60 years who were admitted to 25 hospitals in mainland China with confirmed SARS-CoV-2 infection between December 1, 2022, and February 28, 2023. Efficacy outcomes were all-cause mortality during hospitalization, the proportion of patients discharged with recovery, time to nucleic acid-negative conversion (T NANC), time to symptom improvement (T SI), and time of hospital stay (T HS). Safety was also assessed. Among the 5884 participants identified, 1999 received azvudine, and 1999 matched controls were included after exclusion and propensity score matching. Azvudine recipients exhibited lower all-cause mortality compared with controls in the overall population (13.3% vs. 17.1%, RR, 0.78; 95% CI, 0.67-0.90; P = 0.001) and in the severe subgroup (25.7% vs. 33.7%; RR, 0.76; 95% CI, 0.66-0.88; P < 0.001). A higher proportion of patients discharged with recovery, and a shorter T NANC were associated with azvudine recipients, especially in the severe subgroup. The incidence of adverse events in azvudine recipients was comparable to that in the control group (2.3% vs. 1.7%, P = 0.170). In conclusion, azvudine showed efficacy and safety in older patients hospitalized with COVID-19 during the SARS-CoV-2 omicron wave in China.
7.Effect of azvudine on prevention of SARS-CoV-2 infection among population of close contact with families with symptomatic SARS-CoV-2 infection
Chao JIANG ; Xuping DENG ; Hai FAN ; Peng JIANG
Chinese Journal of Nosocomiology 2025;35(18):2736-2740
OBJECTIVE T o explore the effectiveness and safety of azvudine in prevention of SARS-CoV-2 infection among the population of close contact with families with symptomatic SARS-CoV-2 infection.METHODS A total of 64 people who were closely contact with the families with symptomatic SARS-CoV-2 infection and were trea-ted in Ma'anshan People's Hospital from Jan.2023 to Oct.2023 were enrolled in the study and randomly divid-ed into the group A with 22 cases,the group B with 17 cases and the group C with 25 cases.The group A was giv-en 5mg of azvudine,the group B was given 3mg of azvudine plus 2mg of placebo,and the group C was given 5 mg of azvudine;all the three groups were treated for 7 days in total.The incidence of SARS-CoV-2 infection and the levels of interleukin-6(IL-6),C-reactive protein(CRP),immunoglobulin G(IgG)and immunoglobulin M(IgM)were observed among the three groups of research subjects after the drug therapies;the adverse reactions were re-corded during the research period.RESULTS The incidence rate of SARS-CoV-2 infection was 4.55%in the group A,11.76%in the group B,12.00%in the group C,and there was no significant difference(x2=0.921,P=0.631).There were no significant differences in the levels of IL-6,CRP,IgG and IgM among the three groups be-fore and after the drug therapies.The incidence of adverse reactions such as fatigue,cough,hypertriglyceridemia and gastrointestinal tract reactions was 9.09%in the group A after the drug therapies,11.76%in the group B,12.00%in the group C,and there was no significant difference.CONCLUSION There is no significant difference in the effectiveness of azvudine in prevention of SARS-CoV-2 infection among the population of close contact with families with symptomatic SARS-CoV-2 infection,with the safety and tolerance favorable.
8.Diagnostic value of the vesical imaging-reporting and data system in bladder urothelial carcinoma with variant histology
Linjing JIANG ; Xiao YANG ; Lingkai CAI ; Qiang CAO ; Wei TIAN ; Xiaotong LIU ; Bo LIANG ; Meihua JIANG ; Gongcheng WANG ; Qiang SHAO ; Hongliang QUE ; Xuping JIANG ; Qiang LYU
Chinese Journal of Urology 2025;46(10):751-758
Objective:To evaluate the diagnostic value of the vesical imaging-reporting and data system(VI-RADS)for determining muscle invasion in variant histology urothelial carcinoma(VUC)of the bladder.Methods:A retrospective analysis was performed on the pathological and imaging data of 518 bladder cancer patients admitted to Jiangsu Province Hospital between January 2013 and January 2023. Patients were stratified into pure urothelial carcinoma(PUC)group( n = 457)and variant urothelial carcinoma(VUC)group( n = 61)based on the presence of histological variants. In the PUC group,there were 390 males(85.3%)and 67 females(14.7%),with a mean age of(66.9 ± 11.2)years. Tumor characteristics included maximum diameter ≥ 30 mm in 149(32.6%),< 30 mm in 308(67.4%),multiple tumors in 147(32.2%),solitary in 310(67.8%),pedunculated morphology in 143(31.3%)and non-pedunculated in 314(68.7%). Histological grading identified high-grade tumors in 319 patients(69.8%)and low-grade tumors in 138(30.2%). Pathological stage distribution included 191 of T a(41.8%),127 of T 1(27.8%),76 of T 2(16.6%),47 of T 3(10.3%),and 16 of T 4(3.5%)patients. The VUC group included 61 patients,comprising 51 males(83.6%)and 10 females(16.4%),with a mean age of(65.8 ± 11.4)years. Tumor characteristics were maximum diameter ≥ 30 mm in 38(62.3%),< 30 mm in 23(37.7%),multiple tumors in 16(26.2%),solitary in 45(73.8%),pedunculated morphology in 11(18.0%)and non-pedunculated in 50(82.0%). Histological grading identified high-grade tumors in 59 patients(96.7%)and low-grade tumors in 2(3.3%). Pathological stage distribution included 3 of T a(4.9%),15 of T 1(24.6%),15 of T 2(24.6%),20 of T 3(32.8%),and 8 of T 4(13.1%)patients. No statistically significant differences were found between the two groups in gender,age,or tumor multiplicity( P > 0.05). Statistically significant differences were found in pathological grade,pathological stage,maximum tumor diameter,and pedunculated morphology( P < 0.05). Furthermore,an external validation cohort of 278 bladder cancer patients treated between February 2023 and February 2024 from multiple centers(Jiangsu Provincial People’s Hospital,The First Affiliated Hospital of Zhengzhou University,Union Hospital Tongji Medical College Huazhong University of Science and Technology,Jiangsu Provincial Hospital of Traditional Chinese Medicine,Suzhou Municipal Hospital,Huaian First People’s Hospital,Yixing People’s Hospital)was retrospectively analyzed to externally validate the performance of VI-RADS scoring in predicting muscle invasion of VUC. This cohort included a PUC subgroup of 241 patients,comprising 196 males(81.3%)and 45 females(18.7%),with a mean age of(68.0 ± 10.7)years. Tumor characteristics were maximum diameter ≥ 30 mm in 85(35.3%),< 30 mm in 156(64.7%),multiple tumors in 65(27.0%),solitary in 176(73.0%),pedunculated morphology in 76(31.5%)and non-pedunculated in 165(68.5%). Histological grading identified high-grade tumors in 175 patients(72.6%)and low-grade tumors in 66(27.4%). Pathological staging comprised 107 patients of T a(44.4%),78 of T 1(32.4%),22 of T 2(9.1%),22 of T 3(9.1%),and 12 of T 4(5.0%). The VUC subgroup consisted of 37 patients,comprising 29 males(78.4%)and 8 females(21.6%),with a mean age of(70.5 ± 9.5)years. Tumor characteristics were maximum diameter ≥ 30 mm in 23(62.2%),< 30 mm in 14(37.8%),multiple tumors in 9(24.3%),solitary in 28(75.7%),pedunculated morphology in 7(18.9%)and non-pedunculated in 30(81.1%). Histological grading identified high-grade tumors in 36 patients(97.3%)and low-grade tumors in 1(2.7%). Pathological staging comprised 1 patient of T a(2.7%),9 of T 1(24.3%),7 of T 2(18.9%),19 of T 3(51.4%),and 1 of T 4(2.7%). In this validation cohort,no significant differences were found in gender,age,tumor multiplicity,or pedunculated morphology between the PUC and VUC subgroups( P > 0.05). Significant differences were observed in pathological grade,pathological stage,and maximum tumor diameter( P < 0.05). Three radiologists independently reviewed and scored the multiparametric MRI(mp-MRI)in a blinded manner. Inter-reader agreement was assessed using the weighted kappa statistic. Differences in variables between the two groups were compared using t-tests,chi-square tests,or Fisher’s exact test. The diagnostic performance of VI-RADS for muscle invasion in VUC and PUC was comprehensively evaluated using receiver operating characteristic(ROC)curves,the area under the curve(AUC),and cut-off values determined by the Youden’s index. The DeLong test was used to assess whether the diagnostic performance of VI-RADS differed between VUC and PUC. Results:In the retrospective single-center cohort,the AUC of VI-RADS for assessing muscle invasion was 0.895(95% CI 0.864?0.922)in the PUC group,with a cut-off value of > 3,and the AUC was 0.896(95% CI 0.791-0.960)in the VUC group,with a cut-off value of > 3. The difference between the two groups was not statistically significant( P = 0.986). Using a VI-RADS score > 3 as the cut-off value,the accuracy,sensitivity,specificity,positive predictive value(PPV),and negative predictive value(NPV)for diagnosing muscle invasion status in the PUC group were 85.8%(392/457),70.5%(98/139),92.5%(294/318),80.3%(98/122),and 87.8%(294/335),respectively. The corresponding values for the VUC group were 82.0%(50/61),76.7%(33/43),94.4%(17/18),97.1%(33/34),and 63.0%(17/27).In the retrospective multicenter cohort,the AUC of VI-RADS for assessing muscle invasion was 0.891(95% CI 0.845?0.927)in the PUC group,with a cut-off value of > 2,and the AUC was 0.898(95% CI 0.754?0.973)in the VUC group,with a cut-off value of > 3. The difference between the two groups was not statistically significant( P = 0.897). Using a VI-RADS score > 3 as the cut-off value,the accuracy,sensitivity,specificity,PPV,and NPV for diagnosing muscle invasion status in the PUC group were 85.9%(207/241),58.9%(33/56),94.1%(174/185),75.0%(33/44),and 88.3%(174/197),respectively. The corresponding values for the VUC group were 81.1%(30/37),77.8%(21/27),90.0%(9/10),95.5%(21/22),and 60.0%(9/15).In the single-center cohort,the Kappa values for inter-reader agreement in assessing muscle invasion status using VI-RADS were 0.881( P < 0.01)for the PUC group and 0.941( P < 0.01)for the VUC group among the three readers. In the multicenter cohort,the Kappa values were 0.858( P < 0.01)for the PUC group and 0.838( P < 0.01)for the VUC group. Conclusions:VI-RADS demonstrates similarly high diagnostic performance for assessing muscle invasion in both PUC and VUC,which is applicable for diagnosing muscle invasion status in VUC,and shows good inter-reader agreement.
9.Visual analysis of research hotspots in-hospital stroke from Chinese and English literature by CiteSpace
Nan YANG ; Guoyong ZENG ; Hong QIU ; Shuiying ZENG ; Jun LIU ; Qing HUANG ; Xuping JIANG
Chinese Journal of Modern Nursing 2025;31(5):616-622
Objective:To conduct a visual analysis of the research hotspots and development frontiers in-hospital stroke from both Chinese and English literature.Methods:Relevant literature on in-hospital stroke was retrieved from the Web of Science Core Collection, China National Knowledge Infrastructure, and Wanfang Database, with the search period extending from the inception of each database to June 2024. CiteSpace 6.2R3 was used to analyze the cooperation networks of authors, countries/regions, and institutions, and to conduct co-occurrence, clustering, and emerging keyword analyses.Results:A total of 465 English papers and 72 Chinese papers were included, showing a year-on-year increase in the overall number of publications. The research in English literature was concentrated in United States, with close cooperation between European and American countries, and comprehensive universities as the main research institutions. In Chinese literature, major research institutions were located in teaching hospitals, with limited collaboration between institutions. The research hotspots and frontiers can be categorized into three themes: risk factors, reperfusion therapy, and quality improvement.Conclusions:Research in in-hospital stroke in both Chinese and English literature is at a stable development stage, with both commonalities and differences in research directions. Future studies should focus on enhancing cooperation between authors, disciplines, institutions, and countries, further exploring the risk factors and mechanisms of in-hospital stroke, implementing precision treatment, building prevention and treatment systems, and expanding the breadth and depth of research in this field.
10.Diagnostic value of the vesical imaging-reporting and data system in bladder urothelial carcinoma with variant histology
Linjing JIANG ; Xiao YANG ; Lingkai CAI ; Qiang CAO ; Wei TIAN ; Xiaotong LIU ; Bo LIANG ; Meihua JIANG ; Gongcheng WANG ; Qiang SHAO ; Hongliang QUE ; Xuping JIANG ; Qiang LYU
Chinese Journal of Urology 2025;46(10):751-758
Objective:To evaluate the diagnostic value of the vesical imaging-reporting and data system(VI-RADS)for determining muscle invasion in variant histology urothelial carcinoma(VUC)of the bladder.Methods:A retrospective analysis was performed on the pathological and imaging data of 518 bladder cancer patients admitted to Jiangsu Province Hospital between January 2013 and January 2023. Patients were stratified into pure urothelial carcinoma(PUC)group( n = 457)and variant urothelial carcinoma(VUC)group( n = 61)based on the presence of histological variants. In the PUC group,there were 390 males(85.3%)and 67 females(14.7%),with a mean age of(66.9 ± 11.2)years. Tumor characteristics included maximum diameter ≥ 30 mm in 149(32.6%),< 30 mm in 308(67.4%),multiple tumors in 147(32.2%),solitary in 310(67.8%),pedunculated morphology in 143(31.3%)and non-pedunculated in 314(68.7%). Histological grading identified high-grade tumors in 319 patients(69.8%)and low-grade tumors in 138(30.2%). Pathological stage distribution included 191 of T a(41.8%),127 of T 1(27.8%),76 of T 2(16.6%),47 of T 3(10.3%),and 16 of T 4(3.5%)patients. The VUC group included 61 patients,comprising 51 males(83.6%)and 10 females(16.4%),with a mean age of(65.8 ± 11.4)years. Tumor characteristics were maximum diameter ≥ 30 mm in 38(62.3%),< 30 mm in 23(37.7%),multiple tumors in 16(26.2%),solitary in 45(73.8%),pedunculated morphology in 11(18.0%)and non-pedunculated in 50(82.0%). Histological grading identified high-grade tumors in 59 patients(96.7%)and low-grade tumors in 2(3.3%). Pathological stage distribution included 3 of T a(4.9%),15 of T 1(24.6%),15 of T 2(24.6%),20 of T 3(32.8%),and 8 of T 4(13.1%)patients. No statistically significant differences were found between the two groups in gender,age,or tumor multiplicity( P > 0.05). Statistically significant differences were found in pathological grade,pathological stage,maximum tumor diameter,and pedunculated morphology( P < 0.05). Furthermore,an external validation cohort of 278 bladder cancer patients treated between February 2023 and February 2024 from multiple centers(Jiangsu Provincial People’s Hospital,The First Affiliated Hospital of Zhengzhou University,Union Hospital Tongji Medical College Huazhong University of Science and Technology,Jiangsu Provincial Hospital of Traditional Chinese Medicine,Suzhou Municipal Hospital,Huaian First People’s Hospital,Yixing People’s Hospital)was retrospectively analyzed to externally validate the performance of VI-RADS scoring in predicting muscle invasion of VUC. This cohort included a PUC subgroup of 241 patients,comprising 196 males(81.3%)and 45 females(18.7%),with a mean age of(68.0 ± 10.7)years. Tumor characteristics were maximum diameter ≥ 30 mm in 85(35.3%),< 30 mm in 156(64.7%),multiple tumors in 65(27.0%),solitary in 176(73.0%),pedunculated morphology in 76(31.5%)and non-pedunculated in 165(68.5%). Histological grading identified high-grade tumors in 175 patients(72.6%)and low-grade tumors in 66(27.4%). Pathological staging comprised 107 patients of T a(44.4%),78 of T 1(32.4%),22 of T 2(9.1%),22 of T 3(9.1%),and 12 of T 4(5.0%). The VUC subgroup consisted of 37 patients,comprising 29 males(78.4%)and 8 females(21.6%),with a mean age of(70.5 ± 9.5)years. Tumor characteristics were maximum diameter ≥ 30 mm in 23(62.2%),< 30 mm in 14(37.8%),multiple tumors in 9(24.3%),solitary in 28(75.7%),pedunculated morphology in 7(18.9%)and non-pedunculated in 30(81.1%). Histological grading identified high-grade tumors in 36 patients(97.3%)and low-grade tumors in 1(2.7%). Pathological staging comprised 1 patient of T a(2.7%),9 of T 1(24.3%),7 of T 2(18.9%),19 of T 3(51.4%),and 1 of T 4(2.7%). In this validation cohort,no significant differences were found in gender,age,tumor multiplicity,or pedunculated morphology between the PUC and VUC subgroups( P > 0.05). Significant differences were observed in pathological grade,pathological stage,and maximum tumor diameter( P < 0.05). Three radiologists independently reviewed and scored the multiparametric MRI(mp-MRI)in a blinded manner. Inter-reader agreement was assessed using the weighted kappa statistic. Differences in variables between the two groups were compared using t-tests,chi-square tests,or Fisher’s exact test. The diagnostic performance of VI-RADS for muscle invasion in VUC and PUC was comprehensively evaluated using receiver operating characteristic(ROC)curves,the area under the curve(AUC),and cut-off values determined by the Youden’s index. The DeLong test was used to assess whether the diagnostic performance of VI-RADS differed between VUC and PUC. Results:In the retrospective single-center cohort,the AUC of VI-RADS for assessing muscle invasion was 0.895(95% CI 0.864?0.922)in the PUC group,with a cut-off value of > 3,and the AUC was 0.896(95% CI 0.791-0.960)in the VUC group,with a cut-off value of > 3. The difference between the two groups was not statistically significant( P = 0.986). Using a VI-RADS score > 3 as the cut-off value,the accuracy,sensitivity,specificity,positive predictive value(PPV),and negative predictive value(NPV)for diagnosing muscle invasion status in the PUC group were 85.8%(392/457),70.5%(98/139),92.5%(294/318),80.3%(98/122),and 87.8%(294/335),respectively. The corresponding values for the VUC group were 82.0%(50/61),76.7%(33/43),94.4%(17/18),97.1%(33/34),and 63.0%(17/27).In the retrospective multicenter cohort,the AUC of VI-RADS for assessing muscle invasion was 0.891(95% CI 0.845?0.927)in the PUC group,with a cut-off value of > 2,and the AUC was 0.898(95% CI 0.754?0.973)in the VUC group,with a cut-off value of > 3. The difference between the two groups was not statistically significant( P = 0.897). Using a VI-RADS score > 3 as the cut-off value,the accuracy,sensitivity,specificity,PPV,and NPV for diagnosing muscle invasion status in the PUC group were 85.9%(207/241),58.9%(33/56),94.1%(174/185),75.0%(33/44),and 88.3%(174/197),respectively. The corresponding values for the VUC group were 81.1%(30/37),77.8%(21/27),90.0%(9/10),95.5%(21/22),and 60.0%(9/15).In the single-center cohort,the Kappa values for inter-reader agreement in assessing muscle invasion status using VI-RADS were 0.881( P < 0.01)for the PUC group and 0.941( P < 0.01)for the VUC group among the three readers. In the multicenter cohort,the Kappa values were 0.858( P < 0.01)for the PUC group and 0.838( P < 0.01)for the VUC group. Conclusions:VI-RADS demonstrates similarly high diagnostic performance for assessing muscle invasion in both PUC and VUC,which is applicable for diagnosing muscle invasion status in VUC,and shows good inter-reader agreement.

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