1.Enhanced radiotheranostic targeting of integrin α5β1 with PEGylation-enabled peptide multidisplay platform (PEGibody): A strategy for prolonged tumor retention with fast blood clearance.
Siqi ZHANG ; Xiaohui MA ; Jiang WU ; Jieting SHEN ; Yuntao SHI ; Xingkai WANG ; Lin XIE ; Xiaona SUN ; Yuxuan WU ; Hao TIAN ; Xin GAO ; Xueyao CHEN ; Hongyi HUANG ; Lu CHEN ; Xuekai SONG ; Qichen HU ; Hailong ZHANG ; Feng WANG ; Zhao-Hui JIN ; Ming-Rong ZHANG ; Rui WANG ; Kuan HU
Acta Pharmaceutica Sinica B 2025;15(2):692-706
Peptide-based radiopharmaceuticals targeting integrin α5β1 show promise for precise tumor diagnosis and treatment. However, current peptide-based radioligands that target α5β1 demonstrate inadequate in vivo performance owing to limited tumor retention. The use of PEGylation to enhance the tumor retention of radiopharmaceuticals by prolonging blood circulation time poses a risk of increased blood toxicity. Therefore, a PEGylation strategy that boosts tumor retention while minimizing blood circulation time is urgently needed. Here, we developed a PEGylation-enabled peptide multidisplay platform (PEGibody) for PR_b, an α5β1 targeting peptide. PEGibody generation involved PEGylation and self-assembly. [64Cu]QM-2303 PEGibodies displayed spherical nanoparticles ranging from 100 to 200 nm in diameter. Compared with non-PEGylated radioligands, [64Cu]QM-2303 demonstrated enhanced tumor retention time due to increased binding affinity and stability. Importantly, the biodistribution analysis confirmed rapid clearance of [64Cu]QM-2303 from the bloodstream. Administration of a single dose of [177Lu]QM-2303 led to robust antitumor efficacy. Furthermore, [64Cu]/[177Lu]QM-2303 exhibited low hematological and organ toxicity in both healthy and tumor-bearing mice. Therefore, this study presents a PEGibody-based radiotheranostic approach that enhances tumor retention time and provides long-lasting antitumor effects without prolonging blood circulation lifetime. The PEGibody-based radiopharmaceutical [64Cu]/[177Lu]QM-2303 shows great potential for positron emission tomography imaging-guided targeted radionuclide therapy for α5β1-overexpressing tumors.
2.Fibroblast activation protein targeting radiopharmaceuticals: From drug design to clinical translation.
Yuxuan WU ; Xingkai WANG ; Xiaona SUN ; Xin GAO ; Siqi ZHANG ; Jieting SHEN ; Hao TIAN ; Xueyao CHEN ; Hongyi HUANG ; Shuo JIANG ; Boyang ZHANG ; Yingzi ZHANG ; Minzi LU ; Hailong ZHANG ; Zhicheng SUN ; Ruping LIU ; Hong ZHANG ; Ming-Rong ZHANG ; Kuan HU ; Rui WANG
Acta Pharmaceutica Sinica B 2025;15(9):4511-4542
The activation proteins released by fibroblasts in the tumor microenvironment regulate tumor growth, migration, and treatment response, thereby influencing tumor progression and therapeutic outcomes. Owing to the proliferation and metastasis of tumors, fibroblast activation protein (FAP) is typically highly expressed in the tumor stroma, whereas it is nearly absent in adult normal tissues and benign lesions, making it an attractive target for precision medicine. Radiolabeled agents targeting FAP have the potential for targeted cancer diagnosis and therapy. This comprehensive review aims to describe the evolution of FAPI-based radiopharmaceuticals and their structural optimization. Within its scope, this review summarizes the advances in the use of radiolabeled small molecule inhibitors for tumor imaging and therapy as well as the modification strategies for FAPIs, combined with insights from structure-activity relationships and clinical studies, providing a valuable perspective for radiopharmaceutical clinical development and application.
3.Construction and value of maintenance model of ophthalmic equipment of hospital based on Delphi method
Guixin ZHANG ; Wei WANG ; Xueyao WANG ; Huimin CHEN ; Jianying YANG
China Medical Equipment 2025;22(5):137-141
Objective:To construct a maintenance model of ophthalmic equipment of hospital based on Delphi method,so as to provide a new idea in management for ophthalmic equipment.Methods:The maintenance evaluation system of ophthalmic equipment was constructed by Delphi method,and the analytic hierarchy process(AHP)was applied to determine weight of evaluation index of equipment so as to standardize the management for ophthalmic equipment.A total of thirty used equipment that related to diagnosis and treatment for eye disease in Eye Hospital of China Academy of Chinese Medical Sciences from January 2022 to January 2023 were selected.According to different management modes,the conventional management mode(15 equipment)and Delphi method management mode(15 devices)were adopted respectively to manage equipment.A self-made questionnaire was adopted to investigate the satisfaction degree of medical staffs of the department of ophthalmology,and staffs of purchasing equipment for clinical configuration and use of ophthalmic equipment.The standardization degree of operation management for ophthalmic equipment,operation quality of equipment and satisfaction of medical staffs for clinical configuration of the two management modes were compared.Results:The scores of standardization degree of operation,disinfection and sterilization,maintenance and fault repair were respectively(92.14±5.36),(90.56±6.23),(91.98±5.65)and(92.16±6.36)after the Delphi method were adopted,which were higher than these of conventional management mode,and the differences of them were statistically significant(t=14.809,14.627,16.126,14.872,P<0.05).The average"power on"rate,operation rate,pass rate of acceptance and growth amplitude of cost-benefit of ophthalmic equipment were respectively(90.23±2.05)%,(96.36±3.98)%and(7.66±1.69)%after management with Delphi method was adopted,all of which were higher than these of conventional management mode,and the differences of them were statistically significant(t=9.649,4.248,8.479,16.867,P<0.05).The satisfaction rates of medical staffs of ophthalmic department and staffs of purchasing equipment for the rationality of clinical allocation process,standardization of system and effectiveness of quality of ophthalmic department of adopting Delphi method management mode were respectively 93.33%,93.33%and 90%,all of which were higher than those of conventional management mode,and the differences were statistically significant(x2=7.952,6.667,7.200,P<0.05).Conclusion:The application of the maintenance model of ophthalmic equipment of hospital based on Delphi method can enhance the qualities of managing and operating equipment,and improve the service level of equipment in management for ophthalmic equipment.
4.Exon Sequencing of HNF1β in Chinese Patients with Early-Onset Diabetes
Siqian GONG ; Hong LIAN ; Yating LI ; Xiaoling CAI ; Wei LIU ; Yingying LUO ; Meng LI ; Si-min ZHANG ; Rui ZHANG ; Lingli ZHOU ; Yu ZHU ; Qian REN ; Xiuying ZHANG ; Jing CHEN ; Jing WU ; Xianghai ZHOU ; Xirui WANG ; Xueyao HAN ; Linong JI
Diabetes & Metabolism Journal 2025;49(2):321-330
Background:
Maturity-onset diabetes of the young (MODY) due to variants of hepatocyte nuclear factor 1-beta (HNF1β) (MODY5) has not been well studied in the Chinese population. This study aimed to estimate its prevalence and evaluate the application of a clinical screening method (Faguer score) in Chinese early-onset diabetes (EOD) patients.
Methods:
Among 679 EOD patients clinically diagnosed with type 2 diabetes mellitus (age at diagnosis ≤40 years), the exons of HNF1β were sequenced. Functional impact of rare variants was evaluated using a dual-luciferase reporter system. Faguer scores ≥8 prompted multiplex ligation-dependent probe amplification (MLPA) for large deletions. Pathogenicity of HNF1β variants was assessed following the American College of Medical Genetics and Genomics (ACMG) guidelines.
Results:
Two rare HNF1β missense mutations (E105K and G454R) were identified by sequencing in five patients, showing functional impact in vitro. Another patient was found to have a whole-gene deletion by MLPA in 22 patients with the Faguer score above 8. Following ACMG guidelines, six patients carrying pathogenic or likely pathogenic variant were diagnosed with MODY5. The estimated prevalence of MODY5 in Chinese EOD patients was approximately 0.9% or higher.
Conclusion
MODY5 is not uncommon in China. The Faguer score is helpful in deciding whether to perform MLPA analysis on patients with negative sequencing results.
5.Identification of novel pathogenic variants in genes related to pancreatic β cell function: A multi-center study in Chinese with young-onset diabetes.
Fan YU ; Yinfang TU ; Yanfang ZHANG ; Tianwei GU ; Haoyong YU ; Xiangyu MENG ; Si CHEN ; Fengjing LIU ; Ke HUANG ; Tianhao BA ; Siqian GONG ; Danfeng PENG ; Dandan YAN ; Xiangnan FANG ; Tongyu WANG ; Yang HUA ; Xianghui CHEN ; Hongli CHEN ; Jie XU ; Rong ZHANG ; Linong JI ; Yan BI ; Xueyao HAN ; Hong ZHANG ; Cheng HU
Chinese Medical Journal 2025;138(9):1129-1131
6.Exon Sequencing of HNF1β in Chinese Patients with Early-Onset Diabetes
Siqian GONG ; Hong LIAN ; Yating LI ; Xiaoling CAI ; Wei LIU ; Yingying LUO ; Meng LI ; Si-min ZHANG ; Rui ZHANG ; Lingli ZHOU ; Yu ZHU ; Qian REN ; Xiuying ZHANG ; Jing CHEN ; Jing WU ; Xianghai ZHOU ; Xirui WANG ; Xueyao HAN ; Linong JI
Diabetes & Metabolism Journal 2025;49(2):321-330
Background:
Maturity-onset diabetes of the young (MODY) due to variants of hepatocyte nuclear factor 1-beta (HNF1β) (MODY5) has not been well studied in the Chinese population. This study aimed to estimate its prevalence and evaluate the application of a clinical screening method (Faguer score) in Chinese early-onset diabetes (EOD) patients.
Methods:
Among 679 EOD patients clinically diagnosed with type 2 diabetes mellitus (age at diagnosis ≤40 years), the exons of HNF1β were sequenced. Functional impact of rare variants was evaluated using a dual-luciferase reporter system. Faguer scores ≥8 prompted multiplex ligation-dependent probe amplification (MLPA) for large deletions. Pathogenicity of HNF1β variants was assessed following the American College of Medical Genetics and Genomics (ACMG) guidelines.
Results:
Two rare HNF1β missense mutations (E105K and G454R) were identified by sequencing in five patients, showing functional impact in vitro. Another patient was found to have a whole-gene deletion by MLPA in 22 patients with the Faguer score above 8. Following ACMG guidelines, six patients carrying pathogenic or likely pathogenic variant were diagnosed with MODY5. The estimated prevalence of MODY5 in Chinese EOD patients was approximately 0.9% or higher.
Conclusion
MODY5 is not uncommon in China. The Faguer score is helpful in deciding whether to perform MLPA analysis on patients with negative sequencing results.
7.Exon Sequencing of HNF1β in Chinese Patients with Early-Onset Diabetes
Siqian GONG ; Hong LIAN ; Yating LI ; Xiaoling CAI ; Wei LIU ; Yingying LUO ; Meng LI ; Si-min ZHANG ; Rui ZHANG ; Lingli ZHOU ; Yu ZHU ; Qian REN ; Xiuying ZHANG ; Jing CHEN ; Jing WU ; Xianghai ZHOU ; Xirui WANG ; Xueyao HAN ; Linong JI
Diabetes & Metabolism Journal 2025;49(2):321-330
Background:
Maturity-onset diabetes of the young (MODY) due to variants of hepatocyte nuclear factor 1-beta (HNF1β) (MODY5) has not been well studied in the Chinese population. This study aimed to estimate its prevalence and evaluate the application of a clinical screening method (Faguer score) in Chinese early-onset diabetes (EOD) patients.
Methods:
Among 679 EOD patients clinically diagnosed with type 2 diabetes mellitus (age at diagnosis ≤40 years), the exons of HNF1β were sequenced. Functional impact of rare variants was evaluated using a dual-luciferase reporter system. Faguer scores ≥8 prompted multiplex ligation-dependent probe amplification (MLPA) for large deletions. Pathogenicity of HNF1β variants was assessed following the American College of Medical Genetics and Genomics (ACMG) guidelines.
Results:
Two rare HNF1β missense mutations (E105K and G454R) were identified by sequencing in five patients, showing functional impact in vitro. Another patient was found to have a whole-gene deletion by MLPA in 22 patients with the Faguer score above 8. Following ACMG guidelines, six patients carrying pathogenic or likely pathogenic variant were diagnosed with MODY5. The estimated prevalence of MODY5 in Chinese EOD patients was approximately 0.9% or higher.
Conclusion
MODY5 is not uncommon in China. The Faguer score is helpful in deciding whether to perform MLPA analysis on patients with negative sequencing results.
8.Exon Sequencing of HNF1β in Chinese Patients with Early-Onset Diabetes
Siqian GONG ; Hong LIAN ; Yating LI ; Xiaoling CAI ; Wei LIU ; Yingying LUO ; Meng LI ; Si-min ZHANG ; Rui ZHANG ; Lingli ZHOU ; Yu ZHU ; Qian REN ; Xiuying ZHANG ; Jing CHEN ; Jing WU ; Xianghai ZHOU ; Xirui WANG ; Xueyao HAN ; Linong JI
Diabetes & Metabolism Journal 2025;49(2):321-330
Background:
Maturity-onset diabetes of the young (MODY) due to variants of hepatocyte nuclear factor 1-beta (HNF1β) (MODY5) has not been well studied in the Chinese population. This study aimed to estimate its prevalence and evaluate the application of a clinical screening method (Faguer score) in Chinese early-onset diabetes (EOD) patients.
Methods:
Among 679 EOD patients clinically diagnosed with type 2 diabetes mellitus (age at diagnosis ≤40 years), the exons of HNF1β were sequenced. Functional impact of rare variants was evaluated using a dual-luciferase reporter system. Faguer scores ≥8 prompted multiplex ligation-dependent probe amplification (MLPA) for large deletions. Pathogenicity of HNF1β variants was assessed following the American College of Medical Genetics and Genomics (ACMG) guidelines.
Results:
Two rare HNF1β missense mutations (E105K and G454R) were identified by sequencing in five patients, showing functional impact in vitro. Another patient was found to have a whole-gene deletion by MLPA in 22 patients with the Faguer score above 8. Following ACMG guidelines, six patients carrying pathogenic or likely pathogenic variant were diagnosed with MODY5. The estimated prevalence of MODY5 in Chinese EOD patients was approximately 0.9% or higher.
Conclusion
MODY5 is not uncommon in China. The Faguer score is helpful in deciding whether to perform MLPA analysis on patients with negative sequencing results.
9.Construction and value of maintenance model of ophthalmic equipment of hospital based on Delphi method
Guixin ZHANG ; Wei WANG ; Xueyao WANG ; Huimin CHEN ; Jianying YANG
China Medical Equipment 2025;22(5):137-141
Objective:To construct a maintenance model of ophthalmic equipment of hospital based on Delphi method,so as to provide a new idea in management for ophthalmic equipment.Methods:The maintenance evaluation system of ophthalmic equipment was constructed by Delphi method,and the analytic hierarchy process(AHP)was applied to determine weight of evaluation index of equipment so as to standardize the management for ophthalmic equipment.A total of thirty used equipment that related to diagnosis and treatment for eye disease in Eye Hospital of China Academy of Chinese Medical Sciences from January 2022 to January 2023 were selected.According to different management modes,the conventional management mode(15 equipment)and Delphi method management mode(15 devices)were adopted respectively to manage equipment.A self-made questionnaire was adopted to investigate the satisfaction degree of medical staffs of the department of ophthalmology,and staffs of purchasing equipment for clinical configuration and use of ophthalmic equipment.The standardization degree of operation management for ophthalmic equipment,operation quality of equipment and satisfaction of medical staffs for clinical configuration of the two management modes were compared.Results:The scores of standardization degree of operation,disinfection and sterilization,maintenance and fault repair were respectively(92.14±5.36),(90.56±6.23),(91.98±5.65)and(92.16±6.36)after the Delphi method were adopted,which were higher than these of conventional management mode,and the differences of them were statistically significant(t=14.809,14.627,16.126,14.872,P<0.05).The average"power on"rate,operation rate,pass rate of acceptance and growth amplitude of cost-benefit of ophthalmic equipment were respectively(90.23±2.05)%,(96.36±3.98)%and(7.66±1.69)%after management with Delphi method was adopted,all of which were higher than these of conventional management mode,and the differences of them were statistically significant(t=9.649,4.248,8.479,16.867,P<0.05).The satisfaction rates of medical staffs of ophthalmic department and staffs of purchasing equipment for the rationality of clinical allocation process,standardization of system and effectiveness of quality of ophthalmic department of adopting Delphi method management mode were respectively 93.33%,93.33%and 90%,all of which were higher than those of conventional management mode,and the differences were statistically significant(x2=7.952,6.667,7.200,P<0.05).Conclusion:The application of the maintenance model of ophthalmic equipment of hospital based on Delphi method can enhance the qualities of managing and operating equipment,and improve the service level of equipment in management for ophthalmic equipment.
10.Gastric filling ultrasound for diagnosing dysphagiaafter surgical operation of hiatal hernia
Huizhen YU ; Shuang WU ; Shihong LI ; Xueyao TANG ; Xishu CHEN ; Hong ZHOU ; Yang ZHOU
Chinese Journal of Medical Imaging Technology 2024;40(10):1538-1541
Objective To observe the value of gastric filling ultrasound(GFUS)for diagnosing dysphagia after surgical operation of hiatal hernia(HH).Methods Totally 71 HH patients who underwent laparoscopic HH repair and fundoplication surgery were retrospectively enrolled and divided into dysphagia group(n=23)and non dysphagia group(n=48)according to postoperative Saeed scores.GFUS parameters,including inner diameter of esophageal hiatus lumen(IDE),wall thickness of abdominal esophageal(WTE)and inner diameter of the esophageal lumen at the fold(FIDE)were compared between groups,and their value of diagnosing postoperative dysphagia were analyzed.Results In dysphagia group,IDE and FIDE were lower,while WTE was higher than those in non dysphagia group(all P<0.05).Low IDE and high WTE were both independent risk factors of postoperative dysphagia in HH patients.The sensitivity,specificity and area under the curve(AUC)of IDE for diagnosing dysphagia after surgical operation of HH was 82.64%,66.69%and 0.773,of WTE was 82.59%,68.73%and 0.793,of their combination was 88.89%,77.59%and 0.843,respectively.The AUC of the combination of IDE and WTE was higher than that of IDE and WTE alone(Z=1.328,1.364,P=0.044,0.043).Conclusion Combination of GFUS parameters IDE and WTE was valuable for diagnosing dysphagia after surgical operation of HH.

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