1.A comparative study of the diagnostic efficacy of 68Ga-PSMA-617 PET/CT versus mpMRI for prostate cancer with extraprostatic extension and seminal vesicle invasion
Yinzhao WANG ; Xiaomei GAO ; Yongxiang TANG ; Xiaoping YI ; Jinwei ZHANG ; Shuo HU ; Minfeng CHEN ; Lin QI ; Yi CAI
Chinese Journal of Urology 2025;46(1):23-29
Objective:To compare the diagnostic efficacy of 68Ga-prostate-specific membrane antigen (PSMA)-617 PET/CT and multiparametric magnetic resonance imaging (mpMRI) in detecting extraprostatic extension (EPE) and seminal vesicle invasion (SVI) in prostate cancer. Methods:A retrospective analysis was conducted on the clinical data of 113 patients with localized prostate cancer who underwent both 68Ga-PSMA-617 PET/CT and mpMRI at Xiangya Hospital, Central South University, from May 2018 to May 2024 prior to radical prostatectomy (RP). The median age of the patients was 66.0 (61.3, 71.0) years old, with a median body mass index of 28.86 (19.01, 24.77) kg/m 2, and a median prostate-specific antigen (PSA) level of 13.50(9.26, 21.99) ng/ml. The pathological results after RP were used as the gold standard to compare the sensitivity, specificity, positive predictive value, and negative predictive value of the two imaging modalities in diagnosing EPE and SVI. Additionally, the diagnostic value of combining both imaging modalities was explored, employing a parallel strategy where a positive result from either modality was deemed positive, and only when both tests were negative was the result considered negative. Results:Pathological results after RP indicated EPE in 46 cases (40.71%) and SVI in 11 cases (9.70%). In diagnosing EPE, the sensitivity, specificity, positive predictive value, and negative predictive value of 68Ga-PSMA-617 PET/CT were 17.39% (8/46), 97.01% (65/67), 80.00% (8/10), and 63.11% (65/103), respectively, while for mpMRI they were 34.78% (16/46), 83.58% (56/67), 59.26% (16/27), and 65.12% (56/86), respectively. The sensitivity of mpMRI was significantly higher than that of 68Ga-PSMA-617 PET/CT ( P=0.048), while the specificity was the opposite ( P=0.008). When combining both imaging modalities, the sensitivity, specificity, positive predictive value, and negative predictive value were 45.65% (21/46), 80.60% (54/67), 61.76% (21/34), and 68.35% (54/79), respectively. In diagnosing SVI, the sensitivity, specificity, positive predictive value, and negative predictive value of 68Ga-PSMA-617 PET/CT were 27.27% (3/11), 96.08% (98/102), 42.86% (3/7), and 92.45% (98/106), respectively, while for mpMRI they were 36.36% (4/11), 88.24% (90/102), 25.00% (4/16), and 92.78% (90/97), respectively. The specificity of 68Ga-PSMA-617 PET/CT was significantly higher than that of mpMRI ( P=0.033). When combining both imaging modalities, the sensitivity, specificity, positive predictive value, and negative predictive value were 45.45% (5/11), 85.29% (87/102), 25.00% (5/20), and 93.55% (87/93), respectively. Conclusions:mpMRI has higher sensitivity in diagnosing EPE and SVI in prostate cancer, while 68Ga-PSMA-617 PET/CT shows higher specificity. The combined use of both imaging modalities can increase diagnostic sensitivity but may reduce specificity. PSMA PET/MRI may be a more accurate diagnostic tool for discerning EPE and SVI.
2.Evaluation of 18F-FDG PET/CT SUVmax and T/MB ratio in assessing aggressiveness and predicting therapeutic efficacy in non-Hodgkin's lymphoma
Chuanqin ZHANG ; Qi HUANG ; Peiqing YANG ; Zelong FENG ; Fang LI ; Xiaoping LI ; Pan WANG
Chinese Journal of Immunology 2025;41(11):2645-2650
Objective:To investigate factors influencing 18F-FDG PET/CT SUVmax,T/MB ratio and Ki-67 expression in non-Hodgkin's lymphoma(NHL),to analyze their correlations with lymphoma aggressiveness and their potential advantages in predicting therapeutic efficacy.Methods:A retrospective analysis was conducted to investigate correlations between tumor SUVmax,T/MB ratio,and Ki-67 expression with NHL aggressiveness and clinical characteristics in 99 patients;whether SUVmax,T/MB ratio and Ki-67 served as independent prognostic factors influencing therapeutic efficacy was examined,and potential utility of ΔSUVmax and ΔT/MB as biomarkers for treatment response assessment were evaluated.Results:Aggressive NHL demonstrated significantly higher SUVmax,T/MB ratio and Ki-67 level compared to indolent NHL and aggressive/indolent NHL(P<0.05).A pretreatment SUVmax≥9.05,T/MB≥5.115 or Ki-67≥55%could predict clinical remission in NHL patients post-treatment,while post-treatment reductions of ΔSUVmax≥22.65%or ΔT/MB≥34.85%were associated with achieved clinical remission.Conclusion:SUVmax,T/MB ratio and Ki-67 are closely associated with aggressiveness of NHL,which can be predicted whether NHL will be relieved after treatment.ΔSUVmax and ΔT/MB can assess whether NHL has been relieved after treatment.
3.Evaluation of 18F-FDG PET/CT SUVmax and T/MB ratio in assessing aggressiveness and predicting therapeutic efficacy in non-Hodgkin's lymphoma
Chuanqin ZHANG ; Qi HUANG ; Peiqing YANG ; Zelong FENG ; Fang LI ; Xiaoping LI ; Pan WANG
Chinese Journal of Immunology 2025;41(11):2645-2650
Objective:To investigate factors influencing 18F-FDG PET/CT SUVmax,T/MB ratio and Ki-67 expression in non-Hodgkin's lymphoma(NHL),to analyze their correlations with lymphoma aggressiveness and their potential advantages in predicting therapeutic efficacy.Methods:A retrospective analysis was conducted to investigate correlations between tumor SUVmax,T/MB ratio,and Ki-67 expression with NHL aggressiveness and clinical characteristics in 99 patients;whether SUVmax,T/MB ratio and Ki-67 served as independent prognostic factors influencing therapeutic efficacy was examined,and potential utility of ΔSUVmax and ΔT/MB as biomarkers for treatment response assessment were evaluated.Results:Aggressive NHL demonstrated significantly higher SUVmax,T/MB ratio and Ki-67 level compared to indolent NHL and aggressive/indolent NHL(P<0.05).A pretreatment SUVmax≥9.05,T/MB≥5.115 or Ki-67≥55%could predict clinical remission in NHL patients post-treatment,while post-treatment reductions of ΔSUVmax≥22.65%or ΔT/MB≥34.85%were associated with achieved clinical remission.Conclusion:SUVmax,T/MB ratio and Ki-67 are closely associated with aggressiveness of NHL,which can be predicted whether NHL will be relieved after treatment.ΔSUVmax and ΔT/MB can assess whether NHL has been relieved after treatment.
4.A comparative study of the diagnostic efficacy of 68Ga-PSMA-617 PET/CT versus mpMRI for prostate cancer with extraprostatic extension and seminal vesicle invasion
Yinzhao WANG ; Xiaomei GAO ; Yongxiang TANG ; Xiaoping YI ; Jinwei ZHANG ; Shuo HU ; Minfeng CHEN ; Lin QI ; Yi CAI
Chinese Journal of Urology 2025;46(1):23-29
Objective:To compare the diagnostic efficacy of 68Ga-prostate-specific membrane antigen (PSMA)-617 PET/CT and multiparametric magnetic resonance imaging (mpMRI) in detecting extraprostatic extension (EPE) and seminal vesicle invasion (SVI) in prostate cancer. Methods:A retrospective analysis was conducted on the clinical data of 113 patients with localized prostate cancer who underwent both 68Ga-PSMA-617 PET/CT and mpMRI at Xiangya Hospital, Central South University, from May 2018 to May 2024 prior to radical prostatectomy (RP). The median age of the patients was 66.0 (61.3, 71.0) years old, with a median body mass index of 28.86 (19.01, 24.77) kg/m 2, and a median prostate-specific antigen (PSA) level of 13.50(9.26, 21.99) ng/ml. The pathological results after RP were used as the gold standard to compare the sensitivity, specificity, positive predictive value, and negative predictive value of the two imaging modalities in diagnosing EPE and SVI. Additionally, the diagnostic value of combining both imaging modalities was explored, employing a parallel strategy where a positive result from either modality was deemed positive, and only when both tests were negative was the result considered negative. Results:Pathological results after RP indicated EPE in 46 cases (40.71%) and SVI in 11 cases (9.70%). In diagnosing EPE, the sensitivity, specificity, positive predictive value, and negative predictive value of 68Ga-PSMA-617 PET/CT were 17.39% (8/46), 97.01% (65/67), 80.00% (8/10), and 63.11% (65/103), respectively, while for mpMRI they were 34.78% (16/46), 83.58% (56/67), 59.26% (16/27), and 65.12% (56/86), respectively. The sensitivity of mpMRI was significantly higher than that of 68Ga-PSMA-617 PET/CT ( P=0.048), while the specificity was the opposite ( P=0.008). When combining both imaging modalities, the sensitivity, specificity, positive predictive value, and negative predictive value were 45.65% (21/46), 80.60% (54/67), 61.76% (21/34), and 68.35% (54/79), respectively. In diagnosing SVI, the sensitivity, specificity, positive predictive value, and negative predictive value of 68Ga-PSMA-617 PET/CT were 27.27% (3/11), 96.08% (98/102), 42.86% (3/7), and 92.45% (98/106), respectively, while for mpMRI they were 36.36% (4/11), 88.24% (90/102), 25.00% (4/16), and 92.78% (90/97), respectively. The specificity of 68Ga-PSMA-617 PET/CT was significantly higher than that of mpMRI ( P=0.033). When combining both imaging modalities, the sensitivity, specificity, positive predictive value, and negative predictive value were 45.45% (5/11), 85.29% (87/102), 25.00% (5/20), and 93.55% (87/93), respectively. Conclusions:mpMRI has higher sensitivity in diagnosing EPE and SVI in prostate cancer, while 68Ga-PSMA-617 PET/CT shows higher specificity. The combined use of both imaging modalities can increase diagnostic sensitivity but may reduce specificity. PSMA PET/MRI may be a more accurate diagnostic tool for discerning EPE and SVI.
5.Activation of IP10/CXCR3 Signaling is Highly Coincidental with PrP Sc Deposition in the Brains of Scrapie-Infected Mice.
Chen JIA ; Chen CAO ; Hu CHAO ; Yang WEI ; Wang LIN ; Chen DONGDONG ; Wu YUEZHANG ; Shi QI ; Dong XIAOPING
Biomedical and Environmental Sciences 2024;37(11):1235-1251
OBJECTIVE:
To analyze the relationship between Chemokine IP10 and its receptor CXCR3 during prion infection.
METHODS:
We investigated the increases in IP10 signals, primarily localized in neurons within the brains of scrapie-infected mice, using western blotting, ELISA, co-immunoprecipitation, immunohistochemistry, immunofluorescence assays, and RT-PCR.
RESULTS:
Both CXCR3 levels and activation were significantly higher in the brains of scrapie-infected mice and prion-infected SMB-S15 cells. Enhanced CXCR3 expression was predominantly observed in neurons and activated microglia. Morphological colocalization of PrP C/PrP Sc with IP10/CXCR3 was observed in scrapie-infected mouse brains using immunohistochemistry and immunofluorescence. immunohistochemistry (IHC) analysis of whole brain sections further revealed increased accumulation of IP10/CXCR3 specifically in brain regions with higher levels of PrP Sc deposits. Co-immunoprecipitation and biomolecular interaction assays revealed the molecular interactions between PrP and IP10/CXCR3. Notably, a significantly larger amount of IP10 accumulated within prion-infected SMB-S15 cells than in the normal partner cell line, SMB-PS. Importantly, resveratrol treatment effectively suppressed prion replication in SMB-S15 cells, thereby restoring the accumulation and secretion pattern of cellular IP10 similar to that observed in SMB-PS cells.
CONCLUSION
Our data demonstrate that the activation of IP10/CXCR3 signaling in prion-infected brain tissues coincides with PrP Sc deposition. Modulation of IP10/CXCR3 signaling in the brain represents a potential therapeutic target for mitigating the progression of prion diseases.
Animals
;
Receptors, CXCR3/metabolism*
;
Mice
;
Chemokine CXCL10/metabolism*
;
Brain/metabolism*
;
Scrapie/metabolism*
;
Signal Transduction
;
PrPSc Proteins/metabolism*
6.National bloodstream infection bacterial resistance surveillance report(2022): Gram-positive bacteria
Chaoqun YING ; Yunbo CHEN ; Jinru JI ; Zhiying LIU ; Qing YANG ; Haishen KONG ; Haifeng MAO ; Hui DING ; Pengpeng TIAN ; Jiangqin SONG ; Yongyun LIU ; Jiliang WANG ; Yan JIN ; Yuanyuan DAI ; Yizheng ZHOU ; Yan GENG ; Fenghong CHEN ; Lu WANG ; Yanyan LI ; Dan LIU ; Peng ZHANG ; Junmin CAO ; Xiaoyan LI ; Dijing SONG ; Xinhua QIANG ; Yanhong LI ; Qiuying ZHANG ; Guolin LIAO ; Ying HUANG ; Baohua ZHANG ; Liang GUO ; Aiyun LI ; Haiquan KANG ; Donghong HUANG ; Sijin MAN ; Zhuo LI ; Youdong YIN ; Kunpeng LIANG ; Haixin DONG ; Donghua LIU ; Hongyun XU ; Yinqiao DONG ; Rong XU ; Lin ZHENG ; Shuyan HU ; Jian LI ; Qiang LIU ; Liang LUAN ; Jilu SHEN ; Lixia ZHANG ; Bo QUAN ; Xiaoping YAN ; Xiaoyan QI ; Dengyan QIAO ; Weiping LIU ; Xiusan XIA ; Ling MENG ; Jinhua LIANG ; Ping SHEN ; Yonghong XIAO
Chinese Journal of Clinical Infectious Diseases 2024;17(2):99-112
Objective:To report the results of national surveillance on the distribution and antimicrobial resistance profile of clinical Gram-positive bacteria isolates from bloodstream infections in China in 2022.Methods:The clinical isolates of Gram-positive bacteria from blood cultures in member hospitals of National Bloodstream Infection Bacterial Resistant Investigation Collaborative System(BRICS)were collected during January 2022 to December 2022. Antibiotic susceptibility tests were conducted by agar dilution or broth dilution methods recommended by Clinical and Laboratory Standards Institute(CLSI). WHONET 5.6 and SPSS 25.0 software were used to analyze the data.Results:A total of 3 163 strains of Gram-positive pathogens were collected from 51 member units,and the top five bacteria were Staphylococcus aureus( n=1 147,36.3%),coagulase-negative Staphylococci( n=928,29.3%), Enterococcus faecalis( n=369,11.7%), Enterococcus faecium( n=296,9.4%)and alpha-hemolyticus Streptococci( n=192,6.1%). The detection rates of methicillin-resistant Staphylococcus aureus(MRSA)and methicillin-resistant coagulase-negative Staphylococci(MRCNS)were 26.4%(303/1 147)and 66.7%(619/928),respectively. No glycopeptide and daptomycin-resistant Staphylococci were detected. The sensitivity rates of Staphylococcus aureus to cefpirome,rifampin,compound sulfamethoxazole,linezolid,minocycline and tigecycline were all >95.0%. Enterococcus faecium was more prevalent than Enterococcus faecalis. The resistance rates of Enterococcus faecium to vancomycin and teicoplanin were both 0.5%(2/369),and no vancomycin-resistant Enterococcus faecium was detected. The detection rate of MRSA in southern China was significantly lower than that in other regions( χ2=14.578, P=0.002),while the detection rate of MRCNS in northern China was significantly higher than that in other regions( χ2=15.195, P=0.002). The detection rates of MRSA and MRCNS in provincial hospitals were higher than those in municipal hospitals( χ2=13.519 and 12.136, P<0.001). The detection rates of MRSA and MRCNS in economically more advanced regions(per capita GDP≥92 059 Yuan in 2022)were higher than those in economically less advanced regions(per capita GDP<92 059 Yuan)( χ2=9.969 and 7.606, P=0.002和0.006). Conclusions:Among the Gram-positive pathogens causing bloodstream infections in China, Staphylococci is the most common while the MRSA incidence decreases continuously with time;the detection rate of Enterococcus faecium exceeds that of Enterococcus faecalis. The overall prevalence of vancomycin-resistant Enterococci is still at a low level. The composition ratio of Gram-positive pathogens and resistant profiles varies slightly across regions of China,with the prevalence of MRSA and MRCNS being more pronounced in provincial hospitals and areas with a per capita GDP≥92 059 yuan.
7.Effect of differences in health care situations on the survival of patients with sporadic Creutzfeldt-Jakob disease
Weiwei ZHANG ; Donghua ZHOU ; Yuan WANG ; Kang XIAO ; Donglin LIANG ; Wei ZHOU ; Xiaoping DONG ; Qi SHI
Chinese Journal of Experimental and Clinical Virology 2024;38(1):37-42
Objective:To understand the medical care of patients with sporadic Creutzfeldt-Jakob disease in China and its relationship with survival time.Methods:A retrospective analysis was performed on data of 150 patients with sporadic Creutzfeldt-Jakob disease diagnosed by China′s Creutzfeldt-Jakob Disease Surveillance Network during the period of January 1, 2021 to December 31, 2022 in this study, and telephone follow-up with family members was used to obtain information of the patients′ care, treatment, and survival after diagnosis. Survival was estimated by life table method, median survival time and 95% confidence interval ( CI) were calculated by Kaplan-Meier method, log-rank method was used to compare the difference in survival time between different groups, and multifactorial analysis was performed by COX proportional risk regression model regarding the influencing factors on patients′ survival time. Results:The median survival time of 150 patients with sporadic Creutzfeldt-Jakob disease was 6 months, and the cumulative lifetime survival rates at 2, 6, 12, and 18 months were 62%, 39%, 22%, and 9%, respectively. The result of univariate analysis showed that the differences in survival time between groups with the presence or absence of cortical blindness in the first symptom, the presence or absence of respiratory support (oxygen therapy), the presence or absence of adjunctive medication, and the presence or absence of tube feeding (nasogastric) were meaningful ( P<0.1). Multifactorial COX regression analysis showed that the risk of death in patients without adjuvant medication was 1.429 times higher than that in patients with adjuvant medication (95.0% CI: 1.014-2.014), and the risk of death in patients without tube feeding (nasal feeding) was 1.479 times higher than that in patients with tube feeding (nasal feeding) (95% CI: 1.052-2.081). Conclusions:Whether or not adjuvant medication is administered and whether or not tube feeding (nasogastric) is used are factors that affect survival time in patients with sporadic Creutzfeldt-Jakob disease, and the administration of appropriate adjuvant medication and tube feeding (nasogastric) may contribute to prolonging survival time in patients with sporadic Creutzfeldt-Jakob disease.
8.MAX germline mutation-associated pheochromocytoma-paraganglioma syndrome: multiple endocrine neoplasia type 5
Xiaoping QI ; Weiying CHEN ; Xudong FANG ; Bijun LIAN ; Hongyuan YU ; Junwei WANG
Chinese Journal of Surgery 2024;62(8):798-804
The individualized precision management of hereditary pheochromocytoma (PHEO) and paraganglioma (PGL) syndromes (PPGLs) based on molecular diagnosis and molecular subtype is becoming more popular. The newly discovered MAX germline mutation-associated PPGLs are autosomally dominant and rare. To raise awareness and explore the effective management of individual diagnosis and treatment, the relevant literature published between January 2011 and February was systematically reviewed. There were a total of 101 patients in the 77 families, involving all 5 exons, containing 44 types of MAX germline mutations and mostly concentrated in exons 3 and 4 (64.4%), the main mutations were nonsense mutations and missense mutations (72.3%), and some were large fragment deletions or insertions, intron variant, gene fusion mutations were relatively infrequent. Furthermore, about 10% of the patients had a paternal parent-of-origin effect. Among the 101 patients, 96 (95.0%) developed PHEO including 15 metastatic PHEO, 61 bilateral PHEO and 35 unilateral PHEO. The age of diagnosis was (31.7±10.9) years (range: 13 to 80 years). The male to female ratio was 1.2∶1. Eleven were accompanied with chest and abdominal PGL. Eight (7.9%) were accompanied by functional pituitary adenoma. And 12 (11.9%) developed other neuroendocrine tumors (NET), of which 8 were accompanied by PHEO, including 4 hyperparathyroidism, 1 gangliocytoma and neuroblastoma, 1 pancreatic NET, 1 medullary thyroid carcinoma and 1 C cell hyperplasia. Six presented concomitant non-NET, including 1 tongue squamous cell carcinoma, 1 papillary thyroid carcinoma, 1 prostate cancer, 1 renal oncocytoma, 1 breast cancer with renal oncocytoma, and 1 thoracic chondrosarcoma with multifocal adenocarcinoma of lung. The remaining 5 cases (5.0%), including 4 other NET (2 ganglioblastoma, 1 abdominal neuroblastoma and 1 pancreatic NET) and 1 asymptomatic child, did not present PHEO. The MAX germline mutation may cause a novel multiple endocrine neoplasia, which can be described as type 5. A comprehensive baseline assessment of neural crest cell-derived diseases such as PPGL, pituitary adenoma, hyperparathyroidism, and/or gangliocytoma (neuroblastoma) was recommended for all people with MAX germline mutations, and the risk of bilateral and/or metastatic PHEO should also be considered. In contrast, patients with PPGLs combined with other NET, such as functional pituitary adenoma, should undergo genetic testing and pedigree screening that includes at least the MAX gene.
9.Comparison of the predictive value of multiparametric MRI and prostate-specific membrane antigen PET/CT for pelvic lymph node metastasis in prostate cancer
Wei TANG ; Yi CAI ; Yongxiang TANG ; Xiaoping YI ; Xiaomei GAO ; Lin QI
Chinese Journal of Surgery 2024;62(11):1008-1015
Objective:To compare the diagnostic performance of multiparametric magnetic resonance imaging (mpMRI) and prostate-specific membrane antigen (PSMA) PET/CT in detecting pelvic lymph node metastasis in prostate cancer.Methods:This is a retrospective case series study. A retrospective analysis was conducted on the data of 115 prostate cancer patients who underwent both mpMRI and PSMA PET/CT before undergoing radical prostatectomy and extended pelvic lymph node dissection at the Department of Urology, Xiangya Hospital, Central South University, between March 2020 and September 2023. The age ( M(IQR)) was 67(10) years (range: 45 to 84 years), and the body mass index was 24(4) kg/m 2 (range: 18 to 30 kg/m 2). Pathological and imaging data were obtained from the patients. Lymph node pathology results were used as the gold standard to evaluate the diagnostic performance of mpMRI and PSMA PET/CT for detecting pelvic lymph node metastasis in PCa through diagnostic evaluation tests. Comparisons between groups were performed using independent samples t-test, Mann-Whitney U test, or χ2 test. Results:The positive rate for detecting pelvic lymph node metastasis was 18.3% (21/115) with mpMRI and 25.2% (29/115) with PSMA PET/CT. The pathological positive rate for lymph nodes was 28.7% (33/115). In patient-based analysis, the diagnostic sensitivity of PSMA PET/CT was significantly higher than that of mpMRI (63.6% vs. 30.3%, χ2=7.36, P=0.007). In lesion-based analysis, both the sensitivity and positive predictive value of PSMA PET/CT were significantly higher than those of mpMRI (sensitivity: 68.0% vs. 21.6%, χ2=42.20, P<0.01; positive predictive value: 50.0% vs. 23.1%, χ2=7.54, P=0.006). Conclusions:PSMA PET/CT and mpMRI both demonstrates good specificity in predicting pelvic lymph node metastasis in prostate cancer. However, PSMA PET/CT is significantly superior to mpMRI in terms of sensitivity and the detection rate of pathologically positive lymph nodes.
10.Investigation of the inhibitory potential of caffeic acid phenethyl ester on prion replication, amplification, and fibril formation in vitro
Zhiyue CHAO ; Xiaoxi JIA ; Jiafeng ZENG ; Yuezhang WU ; Kang XIAO ; Liping GAO ; Qi SHI ; Xiaoping DONG ; Cao CHEN
Chinese Journal of Preventive Medicine 2024;58(7):1011-1019
Objective:To investigate the effects and possible mechanisms of caffeic acid phenethyl ester (CAPE) on the replication, amplification, and fibre formation of prions (PrP Sc). Methods:The CCK8 assay was used to detect the cell viability of the prion-infected cell model SMB-S15 after CAPE treatment for 3 days and 7 days and the maximum safe concentration of CAPE for SMB-S15 was obtained. The cells were treated with a concentration within a safe range, and the content of PrP Sc in the cells before and after CAPE treatment was analyzed by western blot. Protein misfolding cycle amplification (PMCA) and western blot were used to assess changes in PrP Sc level in amplification products following CAPE treatment. Real-time-quaking induced conversion assay (RT-QuIC) technology was employed to explore the changes in fibril formation before and after CAPE treatment. The binding affinity between CAPE and murine recombinant full-length prion protein was determined using a molecular interaction assay. Results:CCK8 cell viability assay results demonstrated that treatment with 1 μmol/L CAPE for 3 and 7 days did not exhibit statistically significant differences in cell viability compared to the control group (all P<0.05). However, when the concentration of CAPE exceeded 1 μmol/L, a significant reduction in cell viability was observed in cells treated with CAPE for 3 and 7 days, compared to the control group (all P<0.05). Thus, 1 μmol/L was determined as the maximum safe concentration of CAPE treatment for SMB-S15 cells. The western blot results revealed that treatment with CAPE for both 3 and 7 days led to a detectable reduction in the levels of PrP Sc in SMB-S15 cells (all P<0.05). The products of PMCA experiments were assessed using western blot. The findings revealed a significant decrease in the levels of PrP Sc (relative grey value) in the PMCA amplification products of adapted-strains SMB-S15, 139A, and ME7 following treatment with CAPE, as compared to the control group (all P<0.05). The RT-QuIC experimental results demonstrated a reduction in fibril formation (as indicated by ThT peak values) in CAPE-treated mouse-adapted strains 139A, ME7, and SMB-S15, as well as in SMB-S15 cells infected with prions. Furthermore, CAPE exhibited varying degrees of inhibition towards different seed fibrils formation, with statistically significant differences observed (all P<0.05). Notably, CAPE exhibited a more pronounced inhibitory effect on ME7 seed fibrils. Molecular interaction analyses demonstrated significant binding between CAPE and murine recombinant prion protein, and the association constant was (2.92±0.41)×10 -6 mol/L. Conclusions:CAPE inhibits PrP Sc replication, amplification, and fibril formation in vitro possibly due to specific interactions with the prion protein at the molecular level.

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