1.Peptide-based immuno-PET/CT monitoring of dynamic PD-L1 expression during glioblastoma radiotherapy.
Yong WANG ; Kewen HE ; Yang ZHANG ; Yunhao CHEN ; Shijie WANG ; Kunlong ZHAO ; Zhiguo LIU ; Man HU
Journal of Pharmaceutical Analysis 2025;15(3):101082-101082
Real-time, noninvasive programmed death-ligand 1 (PD-L1) testing using molecular imaging has enhanced our understanding of the immune environments of neoplasms and has served as a guide for immunotherapy. However, the utilization of radiotracers in the imaging of human brain tumors using positron emission tomography/computed tomography (PET/CT) remains limited. This investigation involved the synthesis of [18F]AlF-NOTA-PCP2, which is a novel peptide-based radiolabeled tracer that targets PD-L1, and evaluated its imaging capabilities in orthotopic glioblastoma (GBM) models. Using this tracer, we could noninvasively monitor radiation-induced PD-L1 changes in GBM. [18F]AlF-NOTA-PCP2 exhibited high radiochemical purity (>95%) and stability up to 4 h after synthesis. It demonstrated specific, high-affinity binding to PD-L1 in vitro and in vivo, with a dissociation constant of 0.24 nM. PET/CT imaging, integrated with contrast-enhanced magnetic resonance imaging, revealed significant accumulation of [18F]AlF-NOTA-PCP2 in orthotopic tumors, correlating with blood-brain barrier disruption. After radiotherapy (15 Gy), [18F]AlF-NOTA-PCP2 uptake in tumors increased from 9.51% ± 0.73% to 12.04% ± 1.43%, indicating enhanced PD-L1 expression consistent with immunohistochemistry findings. Fractionated radiation (5 Gy × 3) further amplified PD-L1 upregulation (13.9% ± 1.54% ID/cc) compared with a single dose (11.48% ± 1.05% ID/cc). Taken together, [18F]AlF-NOTA-PCP2 may be a valuable tool for noninvasively monitoring PD-L1 expression in brain tumors after radiotherapy.
2.Peptide-based immuno-PET/CT monitoring of dynamic PD-L1 expression during glioblastoma radiotherapy
Yong WANG ; Kewen HE ; Yang ZHANG ; Yunhao CHEN ; Shijie WANG ; Kunlong ZHAO ; Zhiguo LIU ; Man HU
Journal of Pharmaceutical Analysis 2025;15(3):599-609
Real-time,noninvasive programmed death-ligand 1(PD-L1)testing using molecular imaging has enhanced our understanding of the immune environments of neoplasms and has served as a guide for immunotherapy.However,the utilization of radiotracers in the imaging of human brain tumors using positron emission tomography/computed tomography(PET/CT)remains limited.This investigation involved the synthesis of[18F]AlF-NOTA-PCP2,which is a novel peptide-based radiolabeled tracer that targets PD-L1,and evaluated its imaging capabilities in orthotopic glioblastoma(GBM)models.Using this tracer,we could noninvasively monitor radiation-induced PD-L1 changes in GBM.[18F]AlF-NOTA-PCP2 exhibited high radiochemical purity(>95%)and stability up to 4 h after synthesis.It demonstrated specific,high-affinity binding to PD-L1 in vitro and in vivo,with a dissociation constant of 0.24 nM.PET/CT imaging,integrated with contrast-enhanced magnetic resonance imaging,revealed significant accumulation of[18F]AlF-NOTA-PCP2 in orthotopic tumors,correlating with blood-brain barrier disruption.After radiotherapy(15 Gy),[18F]AlF-NOTA-PCP2 uptake in tumors increased from 9.51%±0.73%to 12.04%±1.43%,indicating enhanced PD-L1 expression consistent with immunohisto-chemistry findings.Fractionated radiation(5 Gy × 3)further amplified PD-L1 upregulation(13.9%±1.54%ID/cc)compared with a single dose(11.48%±1.05%ID/cc).Taken together,[18F]AlF-NOTA-PCP2 may be a valuable tool for noninvasively monitoring PD-L1 expression in brain tumors after radiotherapy.
3.The predictive effect of interleukin combined with TPSA and VEGF on biochemical recurrence in prostate cancer patients after surgery
Weiqiang HU ; Kunlong LIU ; Yuefeng DU ; Liuyong ZHANG ; Weimin GAN
International Journal of Surgery 2025;52(8):552-558
Objective:To explore the predictive value of the combined application of total prostate-specific antigen (TPSA), vascular endothelial growth factor A (VEGF-A), and interleukin (IL) in predicting postoperative biochemical recurrence in patients with prostate cancer.Methods:This study adopted a retrospective cohort research method. 202 male prostate cancer patients who visited Xi′an Gaoxin Hospital from April 2021 to January 2024 were selected as the research subjects. The age of the patients was 68(64, 71) years, and their postoperative conditions were classified into the non-recurrence group ( n=144) and the biochemical recurrence group ( n=58). The general clinical data and serumological test indicators SA, free prostate-specific antigen (FPSA), VEGF-A, IL-6, IL-17] were detected and compared between the two groups. Quantitative data with normal distribution were expressed as mean±standard deviation, and the comparison between groups was performed using the independent sample t-test; non-normal distribution quantitative data were expressed as M( Q1, Q3), and the comparison between groups was performed using the Mann-Whitney U test. The comparison between groups of count data was performed using the chi-square test. Through Spearman correlation analysis and multivariate Logistic regression analysis, the risk factors for biochemical recurrence after surgery in prostate cancer patients were screened out, and the efficacy of the combined prediction model based on TPSA, VEGF-A, and IL-17 was evaluated by receiver operating characteristic (ROC) curve, decision curve (DCA), and calibration curve. Results:The average tumor diameter, proportion of positive surgical margins, proportion of seminal vesicle invasion, and proportion of patients with Gleason score 3-5 in the biochemical recurrence group were significantly higher than those in the non-recurrence group ( P<0.05). The serumological indicators TPSA, VEGF-A, IL-6, IL-17 in the biochemical recurrence group were 44.28 (42.37, 48.57) ng/mL, (28.24±3.99) ng/mL, (39.14±2.95) ng/L and (66.64±6.04) pg/mL; those in the non-recurrence group were 41.25 (36.61, 43.56) ng/mL, (23.52±3.75) ng/mL, (37.19±4.19) ng/L, and (57.31±6.63) pg/mL. The biochemical recurrence group was higher than the non-recurrence group, and the difference was statistically significant ( P<0.05). Spearman correlation analysis and Logistic regression analysis found that TPSA, VEGF-A, and IL-17 were risk factors for biochemical recurrence after surgery in prostate cancer patients ( P<0.05); the DCA curve and calibration curve indicated that the combined prediction model based on TPSA, VEGF-A, and IL-17 had good accuracy (Hosmer-Lemeshow P=0.421), and the ROC curve suggested that the efficacy of the above indicators combined for predicting biochemical recurrence after surgery in prostate cancer patients was higher [AUC (95% CI)=0.899 (0.832-0.966)], and higher than the independent predictive efficacy of each indicator. Conclusion:Continuous monitoring of serum TPSA, VEGF-A, and IL-17 levels can effectively predict the risk of postoperative recurrence in prostate cancer patients and also provide biological markers for preventing disease recurrence.
4.UGT1A1 gene mutation spectrum with indirect hyperbilirubinemia in children
Ying SHEN ; Hongmei GUO ; Yucan ZHENG ; Bixia ZHENG ; Kunlong YAN ; Guiping KONG ; Qian LIN ; Yu JIN ; Zhifeng LIU ; Mei LI
Chinese Journal of Hepatology 2024;32(2):119-124
Objective:To explore the relevancy between the uridine diphosphate-glucuronylgly-cosyltransferase 1A1 (UGT1A1) gene mutation and the phenotype of indirect hyperbilirubinemia in children.Methods:Sixteen cases with indirect hyperbilirubinemia who visited the Department of Gastroenterology, Children's Hospital of Nanjing Medical University from July 2013 to November 2019 were retrospectively analyzed and were divided into Gilbert syndrome (GS), Crigler-Najjar syndrome type II (CNS-II), and indirect hyperbilirubinemia groups unexplained by UGT1A1 gene mutations. The differences in gene mutation site information and general clinical data were compared. The association between gene mutation spectrum and bilirubin level was explored by t-test analysis.Results:Ten of the sixteen cases with indirect hyperbilirubinemia had GS, three had CNS-II, and three had indirect hyperbilirubinemia unexplained by UGT1A1 gene mutations. A total of six mutation types were detected, of which c.211G?>?A accounted for 37.5% (6/16), c.1456T?>?G accounted for 62.5% (10/16), and TATA accounted for 37.5% (6/16), respectively. Compared with the GS group, the CNS group had early disease onset incidence, high serum total bilirubin ( t ?=?5.539, P ?0.05), and indirect bilirubin ( t ?=?5.312, P ?0.05). However, there was no significant difference in direct bilirubin levels ( t ?=?1.223, P ?>?0.05) and age of onset ( t ?=?0.3611, P ?>?0.05) between the two groups. There was no significant correlation between the number of UGT1A1 gene mutations and serum bilirubin levels. Children with c.1456T?>?G homozygous mutations had the highest serum bilirubin levels. Conclusion:The common pathogenic variants of the UGT1A1 gene sequence are c.1456T?>?G, c.211G?>?A, and TATA, indicating that these site mutations are related to the occurrence of indirect hyperbilirubinemia and have important guiding significance for the etiological analysis of indirect hyperbilirubinemia in children.
5.Risk factors and predictive effectiveness of PI-RADS after targeted combined system puncture for CsPCa patients with 3 points
Weiqiang HU ; Weimin GAN ; Xiaoqun YAO ; Jianguang HE ; Ning DING ; Kunlong LIU ; Liuyong ZHANG ; Junping WANG ; Hui LIU
Journal of Modern Urology 2023;28(8):692-695
【Objective】 To investigate the risk factors and predictive effectiveness of prostate imaging reporting and data system (PI-RADS) score for patients with clinically significant prostate cancer (CsPCa) whose PI-RADS score was 3, so as to provide evidence for the diagnosis and treatment. 【Methods】 The clinical and multi-parameter magnetic resonance imaging (mpMRI) data of 153 CsPCa patients treated during Jan.2017 and Dec.2021 whose PI-RADS score was 3 were retrospectively analyzed. With PI-RADS score of 3 as the independent risk factor for CsPCa, the other relevant independent risk factors in predicting CsPCa were evaluated. 【Results】 Univariate and multivariate analyses showed that prostate-specific antigen (PSA) density and apparent dispersion coefficient (ADC) were independent risk factors for the diagnosis of CsPCa (P<0.05). Analysis of receiver operating characteristic (ROC) curve showed that combined PSA density and ADC were more effective than PSA density and ADC alone (P<0.05). 【Conclusion】 The combination of PSA density and ADC can guide clinicians to identify high-risk CsPCa patients from patients with PI-RADS score of 3 points.
6. 6,6′-Bieckol induces apoptosis and suppresses TGF-β-induced epithelial-mesenchymal transition in non-small lung cancer cells
Yongxin LI ; Man LIU ; Kunlong YANG ; Jun TIAN
Chinese Herbal Medicines 2022;14(2):254-262
Objective: In this study, the aim was to investigate the inhibitory effect of 6,6′-bieckol on the migration and epithelial-mesenchymal transition (EMT) of non-small cell lung cancer (NSCLC) cells, and explore its potential molecular mechanisms. Methods: Cell migration was measured using a CCK8, wound healing, and transwell migration assay. Apoptosis was determined using an Annexin V/propidium iodide staining. Western blotting and immunofluorescence were used to examine the expression level of apoptosis-related proteins and EMT marker proteins. Results: The results showed that 6,6′-bieckol inhibited migration and induced apoptosis of NSCLC cells. Furthermore, 6,6′-bieckol had significantly up-regulated the E-cadherin and down-regulated Snail1 and Twist1 transcriptional levels. 6,6′-Bieckol might inhibit TGF-β-induced EMT by down-regulating Snail1 and Twist1 and up-regulating E-cadherin in lung cancer cells. Conclusion: It is suggested that 6,6′-bieckol has the potential to be developed as a therapeutic candidate for lung cancer.
7.Study on the correlation between rotavirus infection and Histo-Blood Group Antigens in children with diarrhea in Nanjing
Zhulun ZHUANG ; Kunlong YAN ; Yu JIN ; Zhifeng LIU ; Weixia CHENG
Chinese Journal of Experimental and Clinical Virology 2022;36(6):691-695
Objective:To investigate the prevalence of rotavirus infection and susceptibility to Histo-Blood Group Antigens (HBGAs) in children with diarrhea under 5 years of age in Nanjing.Methods:Stool and corresponding saliva samples were collected from 295 children with acute diarrhea and 150 healthy children. Rotaviruses were detected in stool samples by antigen detection method, and rotavirus positive samples were genotyped by RT-PCR method. HBGA phenotype of saliva samples was determined by anti-tissue blood group monoclonal antibody ELISA method. Rotavirus infection and HBGA susceptibility were analyzed by statistical analysis.Results:In the case group, 139 (47.12%) of 295 samples were rotavirus positive, with G9[P8] genotype being the most common genotype (84.17%, 117/139). The proportion of fever ( χ2=34.81, P<0.001), vomiting ( χ2=25.01, P<0.001) and respiratory symptoms ( χ2=4.73, P=0.03) in rotavirus infected children, which were higher than those in non-rotavirus infected group, and the difference was statistically significant. In the ABO blood group system, type AB children were more likely to have diarrhea (95% CI: 1.029~2.622; P= 0.036), and type B children had a higher risk of rotavirus infection ( OR=1.783, 95% CI: 1.027~3.095, P= 0.039). In the secretory system antigens, secretory children were more prone to diarrhea and rotavirus infection, G9[P8] genotype infection was related to secretory phenotype ( OR=2.854, 95% CI: 1.641~4.962), and non-secretory children ( χ2=5.723, P=0.017) were less susceptible to rotavirus and G9[P8] genotype rotavirus infection. Conclusions:G9[P8] genotype was the main rotavirus infection in diarrhea children under 5 years of age in Nanjing, and individuals with secretory phenotype were more likely to be infected with G9[P8], which provided scientific basis for preventing and controlling rotavirus diarrhea in this area.
8.Clinical features of 40 cases of anti-Ku antibody associated disease
Qihua YANG ; Xin ZHANG ; Kunlong LYU ; Lei ZHANG ; Yujie HE ; Shengyun LIU
Chinese Journal of Rheumatology 2021;25(6):378-382,c6-1
Objective:By analyzing the clinical characteristics of anti-Ku antibody associated disease, this paper aims to improve the diagnosis and treatment level of it.Methods:The clinical symptoms, laboratory tests and prognosis of 40 anti-Ku-antibody positive patients from the First Affiliated Hospital of Zhengzhou University from September 2017 to September 2019 were retrospectively collected, and then hierarchical clustering analyzed.Results:The average age of 40 anti-Ku positive patients was 48±18 years, and the male to female ratio was 1∶4. The average follow-up was (11±7) months, of which 2 cases were accompanied by malignant tumors and 3 cases died. Interstitial lung disease was most common and was found in 24 cases (60%). The most common disease was inflammatory myopathy (11 cases, 28%), followed by systemic lupus erythematosus (SLE) (9 cases, 22%). According to hierarchical cluster analysis, the anti-Ku-antibodies positive patients were divided into 3 groups. Among them, group A had the highest incidence of pulmonary interstitial fibrosis (84%, P<0.01), and the lowest incidence of renal involvement (0, P<0.01), cytopenia (0, P<0.01), serositis (0, P<0.01). Although the incidence of anti-Jo-1 antibody positivity in group A was the highest (16%, P=0.44) but without statistically significant difference. The characters of group A were in line with inflammatory myopathy. Group C had the highest incidence of renal involvement (57%), lupus rash (71%), cytopenia (57%), low complement (71%) and lupus-related antibodies positivity ( P value were all<0.05), which was in line with SLE. These two groups had their own significant biological characteristics, and were rarely overlapped. Conclusion:Anti-Ku antibody appears in a wide spectrum of autoimmune diseases, among which inflammatory myopathy is the most common, followed by SLE. Patients with anti-Ku antibody rarely have SLE and myositis overlapped, and the overall prognosis is good, but it is necessary to be alert to complications, such as tumors.
9.The diagnostic value of neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio in the active period of pediatric Crohn′s disease
Aimin QIAN ; Fengfei JIAO ; Zhihua ZHANG ; Kunlong YAN ; Zhifeng LIU
Chinese Journal of Inflammatory Bowel Diseases 2021;05(1):73-76
Objective:To evaluate the correlation of neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) with the activity of pediatric Crohn′s disease (CD) , and to study the efficacy of NLR and PLR independently and combinedly in predicting active period of pediatric CD.Methods:A total of 43 children with CD (145 clinical records) admitted to Gastroenterology Department of Children′s Hospital of Nanjing Medical University from June 2017 to March 2020 were analyzed retrospectively. According to pediatric Crohn′s disease activity index, the clinical records were divided into inactive group (94 cases) , mild active group (29 cases) , moderate to severe active group (22 cases) . General information of the children and NLR and PLR results of each group on the second day after admission were collected.Results:The levels of NLR and PLR in mild active group and moderate to severe group were higher than those in inactive group [NLR: 2.96 (2.25, 4.12) vs. 1.10 (0.77, 1.92) , 3.25 (2.50, 5.53) vs. 1.10 (0.77, 1.92) ; PLR: 194.97 (143.30, 238.64) vs. 101.83 (81.75, 147.40) , 198.85 (166.95, 244.95) vs. 101.83 (81.75, 147.40) , P<0.001], but there was no significant difference between mild active group and moderate to severe active group. There were a strong positive correlation between NLR and PLR with CD activity ( rs = 0.622, P<0.001; rs = 0.582, P<0.001, respectively) . The cut-off values of NLR and PLR for predicting CD activity were 1.64 and 136.88, and the AUC was 0.877 and 0.855, respectively. The corresponding sensitivity and specificity were 96.08%, 71.28% and 84.31%, 74.47%, respectively. When NLR was combined with PLR, AUC was 0.891, sensitivity was 86.27%, and specificity was 78.72%. Conclusions:NLR and PLR can be used to distinguish the active and inactive periods of pediatric CD. The combination of NLR and PLR can be used to diagnose the active period of pediatric CD with higher AUC, sensitivity and specificity.
10.The diagnostic value of neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio in the active period of pediatric Crohn′s disease
Aimin QIAN ; Fengfei JIAO ; Zhihua ZHANG ; Kunlong YAN ; Zhifeng LIU
Chinese Journal of Inflammatory Bowel Diseases 2021;05(1):73-76
Objective:To evaluate the correlation of neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) with the activity of pediatric Crohn′s disease (CD) , and to study the efficacy of NLR and PLR independently and combinedly in predicting active period of pediatric CD.Methods:A total of 43 children with CD (145 clinical records) admitted to Gastroenterology Department of Children′s Hospital of Nanjing Medical University from June 2017 to March 2020 were analyzed retrospectively. According to pediatric Crohn′s disease activity index, the clinical records were divided into inactive group (94 cases) , mild active group (29 cases) , moderate to severe active group (22 cases) . General information of the children and NLR and PLR results of each group on the second day after admission were collected.Results:The levels of NLR and PLR in mild active group and moderate to severe group were higher than those in inactive group [NLR: 2.96 (2.25, 4.12) vs. 1.10 (0.77, 1.92) , 3.25 (2.50, 5.53) vs. 1.10 (0.77, 1.92) ; PLR: 194.97 (143.30, 238.64) vs. 101.83 (81.75, 147.40) , 198.85 (166.95, 244.95) vs. 101.83 (81.75, 147.40) , P<0.001], but there was no significant difference between mild active group and moderate to severe active group. There were a strong positive correlation between NLR and PLR with CD activity ( rs = 0.622, P<0.001; rs = 0.582, P<0.001, respectively) . The cut-off values of NLR and PLR for predicting CD activity were 1.64 and 136.88, and the AUC was 0.877 and 0.855, respectively. The corresponding sensitivity and specificity were 96.08%, 71.28% and 84.31%, 74.47%, respectively. When NLR was combined with PLR, AUC was 0.891, sensitivity was 86.27%, and specificity was 78.72%. Conclusions:NLR and PLR can be used to distinguish the active and inactive periods of pediatric CD. The combination of NLR and PLR can be used to diagnose the active period of pediatric CD with higher AUC, sensitivity and specificity.

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