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.Clinical application of metagenomic next-generation sequencing for identifying non-tuberculous mycobacteria from bronchoalveolar lavage fluid
Jieyuan ZHENG ; Dan ZHANG ; Jieting ZHOU ; Jingchao WANG ; Lingjun YUAN ; Mengxiao XIE ; Binxiao LI ; Dongsheng HAN
Chinese Journal of Clinical Infectious Diseases 2025;18(1):19-24
Objective:To evaluate the application of metagenomic next-generation sequencing(mNGS)in the identification of non-tuberculous mycobacteria(NTM).Methods:A retrospective analysis was conducted on mNGS results of 358 bronchoalveolar lavage fluid(BALF)samples positive for NTM collected at the First Affiliated Hospital of Zhejiang University School of Medicine from February 2021 to January 2024. The analysis included the distribution of NTM species,the detection of mixed pathogens,and the performance of conventional mycobacterial detection methods.Results:The results showed that 362 strains of 15 NTM species were identified from 350 specimens,8 specimens were not precise to the species level. The most frequently detected species were Mycobacterium intracellulare(37.3%,135/362), Mycobacterium abscessus(26.8%,97/362),followed by Mycobacterium avium(11.0%,40/362), Mycobacterium kansasii(8.0%,29/362)and Mycobacterium chelonae(7.7%,28/362). Single NTM species were detected in 339 specimens,while two or three NTM species were simultaneously detected in 11 specimens(3.1%,11/358). Non-NTM microorganisms co-infected were detected in 53.4%(191/358)of NTM-positive BALF samples,including common pathogens such as Pseudomonas aeruginosa, Staphylococcus aureus,and Aspergillus fumigatus;and difficult-to-identify pathogens such as Legionella pneumophila and Talaromyces marneffei. In NTM-positive patients detected by mNGS,the results supported the diagnosis of NTM infection in 298 cases(298/358,83.2%)and 105 cases(105/358,29.3%)initiated anti-NTM treatment accordingly;while in 60 cases(60/358,16.8%)the positive results were considered as colonization or unrelated to clinical infection. For samples tested with acid-fast staining,mycobacterial liquid culture,and DNA microarray,the positivity rates for NTM were 31.5%(73/232),48.7%(57/117),and 43.0%(46/107),respectively. Conclusions:mNGS demonstrates advantages in identification of NTM. However,the test may detect multiple microorganisms,in that case,the interpretation with clinical and radiological results is requried to determine the main pathogens.
4.Sherlock 3CG Tip Confirmation System in peripherally inserted central catheter placement: a scoping review
Jieting JIANG ; Suqiang DENG ; Hongmei HUANG ; Jing TANG ; Xingyuan DAI ; Bo ZHANG
Chinese Journal of Modern Nursing 2025;31(4):550-555
Objective:To summarize and analyze the literature on the application of the Sherlock 3CG Tip Confirmation System (TCS) in peripherally inserted central catheter (PICC) placement, providing evidence for clinical practice and related research using Sherlock 3CG TCS.Methods:A systematic search was conducted in PubMed, Web of Science, CINAHL, Scopus, Embase, Cochrane Library, China National Knowledge Infrastructure, Wanfang Data, and VIP databases, with the retrieval period covering database inception to November 20, 2023. Two researchers independently extracted data from the included studies, including author, publication year, country, study type, study population, sample size, outcome indicators, and the definition of optimal tip position.Results:A total of 18 studies were included. The primary study population consisted of adults requiring PICC placement, with only one study focusing on children. Outcome indicators evaluated the system 's effectiveness, safety, accuracy, cost-effectiveness, and ease of use. Conclusions:Sherlock 3CG TCS demonstrates good effectiveness and safety, improves the accuracy of PICC tip positioning, is convenient and easy to use, reduces patient burden and healthcare costs, and enhances the confidence and satisfaction of catheter placement personnel. Further large-sample, multicenter randomized controlled trials are needed to validate these findings.
5.Sherlock 3CG Tip Confirmation System in peripherally inserted central catheter placement: a scoping review
Jieting JIANG ; Suqiang DENG ; Hongmei HUANG ; Jing TANG ; Xingyuan DAI ; Bo ZHANG
Chinese Journal of Modern Nursing 2025;31(4):550-555
Objective:To summarize and analyze the literature on the application of the Sherlock 3CG Tip Confirmation System (TCS) in peripherally inserted central catheter (PICC) placement, providing evidence for clinical practice and related research using Sherlock 3CG TCS.Methods:A systematic search was conducted in PubMed, Web of Science, CINAHL, Scopus, Embase, Cochrane Library, China National Knowledge Infrastructure, Wanfang Data, and VIP databases, with the retrieval period covering database inception to November 20, 2023. Two researchers independently extracted data from the included studies, including author, publication year, country, study type, study population, sample size, outcome indicators, and the definition of optimal tip position.Results:A total of 18 studies were included. The primary study population consisted of adults requiring PICC placement, with only one study focusing on children. Outcome indicators evaluated the system 's effectiveness, safety, accuracy, cost-effectiveness, and ease of use. Conclusions:Sherlock 3CG TCS demonstrates good effectiveness and safety, improves the accuracy of PICC tip positioning, is convenient and easy to use, reduces patient burden and healthcare costs, and enhances the confidence and satisfaction of catheter placement personnel. Further large-sample, multicenter randomized controlled trials are needed to validate these findings.
6.Clinical application of metagenomic next-generation sequencing for identifying non-tuberculous mycobacteria from bronchoalveolar lavage fluid
Jieyuan ZHENG ; Dan ZHANG ; Jieting ZHOU ; Jingchao WANG ; Lingjun YUAN ; Mengxiao XIE ; Binxiao LI ; Dongsheng HAN
Chinese Journal of Clinical Infectious Diseases 2025;18(1):19-24
Objective:To evaluate the application of metagenomic next-generation sequencing(mNGS)in the identification of non-tuberculous mycobacteria(NTM).Methods:A retrospective analysis was conducted on mNGS results of 358 bronchoalveolar lavage fluid(BALF)samples positive for NTM collected at the First Affiliated Hospital of Zhejiang University School of Medicine from February 2021 to January 2024. The analysis included the distribution of NTM species,the detection of mixed pathogens,and the performance of conventional mycobacterial detection methods.Results:The results showed that 362 strains of 15 NTM species were identified from 350 specimens,8 specimens were not precise to the species level. The most frequently detected species were Mycobacterium intracellulare(37.3%,135/362), Mycobacterium abscessus(26.8%,97/362),followed by Mycobacterium avium(11.0%,40/362), Mycobacterium kansasii(8.0%,29/362)and Mycobacterium chelonae(7.7%,28/362). Single NTM species were detected in 339 specimens,while two or three NTM species were simultaneously detected in 11 specimens(3.1%,11/358). Non-NTM microorganisms co-infected were detected in 53.4%(191/358)of NTM-positive BALF samples,including common pathogens such as Pseudomonas aeruginosa, Staphylococcus aureus,and Aspergillus fumigatus;and difficult-to-identify pathogens such as Legionella pneumophila and Talaromyces marneffei. In NTM-positive patients detected by mNGS,the results supported the diagnosis of NTM infection in 298 cases(298/358,83.2%)and 105 cases(105/358,29.3%)initiated anti-NTM treatment accordingly;while in 60 cases(60/358,16.8%)the positive results were considered as colonization or unrelated to clinical infection. For samples tested with acid-fast staining,mycobacterial liquid culture,and DNA microarray,the positivity rates for NTM were 31.5%(73/232),48.7%(57/117),and 43.0%(46/107),respectively. Conclusions:mNGS demonstrates advantages in identification of NTM. However,the test may detect multiple microorganisms,in that case,the interpretation with clinical and radiological results is requried to determine the main pathogens.
7.A systematic review of cognitive intervention studies of mindfulness training in older adults
Yiting WEI ; Shaoxia FAN ; Qing GUAN ; Jieting ZHANG ; Wenyi LIN ; Yuejia LUO ; Haobo ZHANG
Chinese Mental Health Journal 2024;38(6):500-509
Mindfulness training has shown beneficial effects on cognitive functions in older adults.Howev-er,the studies on this topic have used different methods and populations,and their results were inconsistent.No sys-tematic review has synthesized and evaluated these findings.This review aims to address this gap by categorizing the studies based on the training methods and cohorts of older adults,and summarizing the effects of mindfulness training on cognitive function.The review finds that mindfulness training had different effects depending on the lev-el of cognitive decline and the training method.Both standardized and unstandardized training methods improved cognitive performance in older adults with normal or subjective cognitive decline.However,the effect of mindful-ness training diminished as cognitive decline worsened,being inconsistent in mild cognitive impairment and non-sig-nificant in dementia.The review also discusses the possible mechanisms and suggested directions for future re-search.
8.Current situation analysis and quality evaluation of ERAS guidelines/consensus in obstetrics and gynecology surgery
Jinlamu YANG ; Ga MEI ; Lishi DONG ; Rongfang ZHENG ; Jinhui TIAN ; Yan ZHANG ; Jieting LIU
Chinese Journal of Pharmacoepidemiology 2024;33(6):652-665
Objective To analyze the current status and quality of existing obstetrics and gynecology enhanced recovery after surgery(ERAS)guidelines/consensus,understand the evidence-based practices in this field,and provide a basis for clinical decision-making.Methods A systematic search of PubMed,CNKI,and other databases,as well as NGC,SIGN,and websites of anesthesia societies domestically and internationally was conducted to obtain relevant guidelines and consensus on ERAS for gynecological surgery.The search was conducted from inception to July 1,2023,and the AGREE Ⅱ and RIGHT tools were used to analyze the current status and quality of the included guidelines/consensus,as well as to conduct a summary of the recommendations.Results A total of 5 guidelines and 10 consensus statements were included.The publication years were from 2018 to 2023,originating from the United States,China,Canada,and the United Kingdom.In the 6 areas evaluated using AGREEⅡ,clarity(66.06%)scored highest,followed by scope and purpose(56.67%),involvement of stakeholders(42.02%),and editorial independence(37.64%)with scores above 30%.The scores for rigor of development(26.88%)and applicability(4.17%)were relatively low.The same items among different evaluators indicated good consistency.The results of the scores in each area were as follows:A-level 2,B-level 13,and no C-level.Two high-quality guidelines were selected.The average RIGHT reporting rate was 44.38%.Subgroup analysis showed that guidelines were higher than consensus statements in the areas of rigor of development and applicability(P<0.05),and that using GRADE was higher than not using(P<0.05).The areas of rigor of development and clarity were higher in foreign guidelines than domestic guidelines(P<0.05),and using evidence grading tools was higher than not using(P<0.05).The summary of the recommendations showed that the quality of the evidence supporting the recommendations was uneven,and some recommendations were not specific enough.Conclusion The quality of the 15 included ERAS guidelines/consensus in obstetrics and gynecology is uneven,and 2 of them can be used as high-quality guidelines for clinical reference.The quality of evidence-based guidelines in foreign countries is higher,and the use rate of GRADE in foreign guidelines is high,most of which can provide clear recommendation strength and evidence level.Chinese guidelines/consensus are of lower quality compared to overseas,and methodology and report quality need further improvement.Overall,it is still necessary to strengthen the formulation of methods and reporting standards,improve the quality of evidence,and refine specific recommendations.
9.Advances in the regulation of autosomal dominant polycystic kidney disease by Hippo signaling pathway
Jieting ZHANG ; Jing XU ; Cheng XUE ; Zhiguo MAO
Chinese Journal of Nephrology 2023;39(3):224-228
The Hippo signaling pathway is highly conserved in evolution, and participates in the regulation of cell proliferation, differentiation, and tissular dynamic balance, and plays an important role in regulating tissue, organ size, and cell number. Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary kidney disease and one of the most common causes of end-stage renal disease. Emerging studies have identified the Hippo signaling pathway is closely related to the occurrence and development of ADPKD. The abnormal activity and expression of the main members of the pathway affect the cilia and cell polarity of renal tubular epithelial cells and induce the formation of renal cysts. The review summarizes the potential mechanism of the Hippo pathway in the pathogenesis of ADPKD, the crosstalk with other signaling pathways, and the variances in different species, and discusses the strategies for the treatment of ADPKD based on the Hippo signaling pathway to provide new strategies for the treatment.
10. Effects and mechanism of dapagliflozin on myocardial injury in type 1 diabetes mice
Xuejiao ZHANG ; Jieting LIU ; Luxin LI ; Peijian CHEN ; Minglu DING ; Mengwei SUN ; Yanhui CHU ; Zhen ZHANG
Chinese Journal of Clinical Pharmacology and Therapeutics 2023;28(3):257-265
AIM: To investigate the effect of dapagliflozin on myocardial injury in type 1 diabetes mice and its mechanism. METHODS: Normal C57BL / 6J male mice were randomly divided into normal control group (Control), diabetes cardiomyopathy group (DCM) and dapagliflozin group (DAPA). The model of diabetes was induced by streptozotocin (STZ) and given maintenance feed. DAPA group was given 10 mg · kg

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