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.Genetic and clinical characteristics of single and compound types of patients with long QT syndrome type 3
Zhonghe ZHANG ; Jing ZUO ; Yan HUANG ; Hongyi DUAN ; Hao XIA ; Hong JIANG ; Dan HU
Chinese Journal of Cardiology 2024;52(7):777-783
Objective:To explore the genetic background and clinical features of patients with long QT syndrome type 3 (LQT3).Methods:This retrospective cohort included patients diagnosed with LQT3 at the Department of Cardiology, Renmin Hospital of Wuhan University from January 1998 to December 2022. Patients were categorized into compound type group and single type group based on the presence of a single SCN5A mutation. The two groups were followed up and the differences in baseline characteristics, electrocardiograms, and clinical events between the two groups and probands were compared. Kaplan-Meier curves were used for survival analysis, and the log-rank test was employed to compare the event-free survival rates of first cardiac events between the groups and probands.Results:A total of 97 LQT3 patients were enrolled, including 59 probands. The age at diagnosis was (23.45±19.86) years, with 46 patients (47.4%) being male. Among them, 89 patients were classified as single type group, while 8 patients were classified as compound type group. Genetic testing identified 49 SCN5A mutations, with missense mutations being the majority (91.8%), primarily located in transmembrane regions (40.8%, n=20), interdomain linker regions (28.6%, n=14), and C-terminus (22.4%, n=11). The first cardiac event occurred in 44 patients (45.4%), with an onset age of (13.82±12.50) years. The main trigger was identified as rest or sleep (54.5%, n=24). Compared with patients in single type group, patients in compound type group were younger at diagnosis ((10.35±10.28) years vs. (24.63±20.13) years, P=0.040), had a significantly higher proportion of syncope (87.5% (7/8) vs. 33.7% (30/89), P=0.009), aborted cardiac arrest (62.5% (5/8) vs. 11.2% (10/89), P=0.001), and a lower incidence of event-free survival rates of first cardiac events (12.5% (1/8) vs.58.4% (52/89), log-rank P=0.001). The probands in compound type group had a significantly higher proportion of aborted cardiac arrest comparing to probands in single type group (62.5% (5/8) vs. 17.6% (9/51), P=0.020), while the difference in the incidence rate of event-free survival rates of first cardiac events between the probands in two groups was not statistically significant (12.5% (1/8) vs. 39.2% (20/51), log-rank P=0.08). Conclusion:Compound type LQT3 patients are not uncommon. Such patients are diagnosed at a younger age and exhibit more severe phenotypes, requiring close follow-up and proactive intervention strategies.
4.A neutrophil-biomimic platform for eradicating metastatic breast cancer stem-like cells by redox microenvironment modulation and hypoxia-triggered differentiation therapy.
Yongchao CHU ; Yifan LUO ; Boyu SU ; Chao LI ; Qin GUO ; Yiwen ZHANG ; Peixin LIU ; Hongyi CHEN ; Zhenhao ZHAO ; Zheng ZHOU ; Yu WANG ; Chen JIANG ; Tao SUN
Acta Pharmaceutica Sinica B 2023;13(1):298-314
Metastasis accounts for 90% of breast cancer deaths, where the lethality could be attributed to the poor drug accumulation at the metastatic loci. The tolerance to chemotherapy induced by breast cancer stem cells (BCSCs) and their particular redox microenvironment further aggravate the therapeutic dilemma. To be specific, therapy-resistant BCSCs can differentiate into heterogeneous tumor cells constantly, and simultaneously dynamic maintenance of redox homeostasis promote tumor cells to retro-differentiate into stem-like state in response to cytotoxic chemotherapy. Herein, we develop a specifically-designed biomimic platform employing neutrophil membrane as shell to inherit a neutrophil-like tumor-targeting capability, and anchored chemotherapeutic and BCSCs-differentiating reagents with nitroimidazole (NI) to yield two hypoxia-responsive prodrugs, which could be encapsulated into a polymeric nitroimidazole core. The platform can actively target the lung metastasis sites of triple negative breast cancer (TNBC), and release the escorted drugs upon being triggered by the hypoxia microenvironment. During the responsiveness, the differentiating agent could promote transferring BCSCs into non-BCSCs, and simultaneously the nitroimidazole moieties conjugated on the polymer and prodrugs could modulate the tumor microenvironment by depleting nicotinamide adenine dinucleotide phosphate hydrogen (NADPH) and amplifying intracellular oxidative stress to prevent tumor cells retro-differentiation into BCSCs. In combination, the BCSCs differentiation and tumor microenvironment modulation synergistically could enhance the chemotherapeutic cytotoxicity, and remarkably suppress tumor growth and lung metastasis. Hopefully, this work can provide a new insight in to comprehensively treat TNBC and lung metastasis using a versatile platform.
5.Study on the Influence of Yunnan Rice Products on Blood Sugar
Murong JIANG ; Yuanqin LEI ; Ke ZHANG ; Qiumei LIU ; Wenli YANG ; Hongyi LIU ; Jie YAN ; Qingwen ZHANG
Journal of Kunming Medical University 2023;44(12):41-45
Objective To explore the effect of Yunnan specialty rice products on blood sugar by measuring the glycemic index of 5 Yunnan special rice foods:rice noodles,rice cakes,rice rolls,sour rice noodles and dry rice noodles.Methods Following the national standard method to determine the carbohydrate content of 5 Yunnan specialty rice products,and the target amount of the test substance was calculated.Food Glycemic Index Determination Method was used to determine the glycemic index of 5 Yunnan specialty rice products and observe their impact on blood sugar.Results The GI value of Yunnan specialty food rice noodle is 63,rice cake is 64,rice roll is 46,sour rice noodles is 38,and dry rice noodles is 33.Conclusion Yunnan specialty foods rice noodle and rice cake belong to medium GI foods,and diabetes patients should reduce consumption;rice roll,sour rice noodles,and dry rice noodles belong to low GI foods and can be a better staple food source for diabetes patients.
6.Role of Cytokines and Related Signaling Pathways in Intervention of Chinese Medicine in Radiation-induced Lung Injury: A Review
Jiayi SHAO ; Mianhua WU ; Yanxia MA ; Zequn JIANG ; Hongyi XU ; Muhan LI
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(22):244-253
Radiation-induced lung injury (RILI), one of the common complications caused by radiotherapy, encompasses two phases: an early phase known as radiation pneumonitis (RP) and a late phase called radiation fibrosis (RF), threatening the life and life quality of patients, with poor prognosis. Accumulating evidence has shown that the occurrence of RILI is related to a variety of cytokines and signaling pathways. This paper summarized the research on the effects of Chinese medicine on RILI from the perspective of cytokines and signaling pathways. Cytokines include transforming growth factor-β1 (TGF-β1), interleukins (ILs), tumor necrosis factor-α (TNF-α), platelet-derived growth factor (PDGF), vascular endothelial growth factor (VEGF), and high mobility group box-1 (HMGB1). Related signaling pathways are phosphatidylinositol-3-kinase/protein kinase B(PI3K/Akt) signaling pathway, mitogen-activated protein kinase (MAPK) signaling pathway, Wnt/β-catenin signaling pathway, Notch1/Jagged1 signaling pathway, and nuclear factor-E2-related factor2/antioxidant response element (Nrf2/ARE) signaling pathway. Cytokines may interfere with RILI progression by initiating various downstream signaling pathways, such as TGF-β1/Smads signaling pathway, TGF-β1/VEGF signaling pathway, TNF-α/nuclear factor-κB (NF-κB) signaling pathway, and HMGB1/Toll-like receptor 4 (TLR4) signaling pathway. In recent years, many scholars have attempted to delay RILI progression by down-regulating the expression of cytokines, antagonizing the effect of cytokines or regulating signaling pathways. It has been verified that many Chinese medicines, Chinese medicine monomers, and compound Chinese medicine prescriptions can inhibit the release of some cytokines or regulate some signaling pathways to reduce the incidence/severity of RILI, with satisfactory therapeutic effects, which have attracted the interest of scholars.
7.Advances in minimally invasive surgery for thyroid tumors
Hongyi JIANG ; Chuanming ZHENG ; Minghua GE
Journal of Surgery Concepts & Practice 2023;28(6):491-495
The incidence of thyroid tumors has been increasing recent years,the importance of quality of life has been more concerned in addition to radical treatment.Traditional open surgery has been unable to meet the needs of all patients.In recent years,the continuous innovation and vigorous development of minimally invasive techniques,including endoscopy,ablation,and robotics,have expanded the range of available surgical options.In this review,we summarized the advancements in minimally invasive surgery for thyroid tumors,focusing on how to select the most appropriate surgical approach based on the patient's condition and develop personalized treatment plans.
8.Short-term outcome of kidney transplantation from deceased donors with nephrolithiasis
Liang TAN ; Lei SONG ; Yixin XIE ; Longkai PENG ; Gongbin LAN ; Hedong ZHANG ; Hongyi JIANG ; Xubiao XIE
Journal of Central South University(Medical Sciences) 2022;47(9):1217-1226
Objective: Shortage of kidney allografts is a major barrier to end-stage renal disease patients receiving kidney transplantation, and it is necessary to enlarge the donor pool and find better ways of using available allografts. The global incidence of nephrolithiasis is increasing, nephrolithiasis affects approximately 10% of adults worldwide, and it also affects the kidney donors. However, there is little information about the use of cadaveric kidney allografts with nephrolithiasis. This study aims to evaluate the safety and outcome of kidney transplantation with allografts from the deceased donors with nephrolithiasis. Methods: A total of 520 deceased donors who was at least 10 years old, and 945 adult recipients with single kidney transplantation at the Department of Kidney Transplantation, the Second Xiangya Hospital from 2016 to 2020 were included in this study. The donors were divided into 2 groups according to nephrolithiasis diagnoses: The donors with nephrolithiasis (D+) and the donors without nephrolithiasis (D?). The recipients were assigned into 3 groups according to their donors and the allografts they received: The allografts from donors without nephrolithiasis (D?K?), the allografts without nephrolithiasis from donors with nephrolithiasis (D+K?), and the allografts with nephrolithiasis (D+K+). The demographic and clinical data of enrolled subjects were retrospectively analyzed. The allograft discard ratio between different donors were analyzed. The one-year survival of allografts and recipients, as well as the allograft function and the complications of kidney transplantation were compared. Results: Fifty out of 520 donors had nephrolithiasis, and the nephrolithiasis incidence was 9.6%. We recovered 1040 kidneys, and total discard rate was 4.4% (46/1040). The D+ group had a rate of 7% discard. The donors with kidney discard accounted for 12% in the D+ group, and this was higher than that of donors in the D? group (5.1%, P<0.05). The total incidence of delayed graft function (DGF) was 7.5%, and there were no significant differences in the incidence of DGF in recipients among the D?K?, D+K?, and D+K+ group (7.5% vs 6.5% vs 8.2%, P>0.05). During the one-year follow-up, 8 allografts lost function and 19 recipients died with a functional allograft. Recipients in the D?K?, D+K?, and D+K+ groups also had no significant difference between a one-year allograft and patient survival rate (P>0.05). However, recipients in the D+K+ group had a higher level of serum creatinine [(139.2±62.46) μmol/L vs (117.19±51.22) μmol/L, P<0.05] and lower estimated glomerular filtration rate [eGFR; (56.67±23.31) mL/(min·1.73 m?2) vs (66.86±21.90) mL/(min·1.73 m?2), P<0.05] compared with recipients in the D?K? group at 12 months after transplantation. During the first year after transplantation, 4 recipients developed urolithiasis, and recipients who received allografts from the D+ group donors had a higher incidence of urolithiasis than those who received allografts from the D? group donors (2.2% vs 0.2%, P<0.05). There were no significant differences in the incidence of urinary tract infections and ureteral strictures at 1 year between recipients of D+ and D? donors (both P>0.05).Conclusion: The cadaveric kidney allografts with nephrolithiasis could be safely used for transplantation, and the short-term outcome is acceptable. However, nephrolithiasis in donors may increase the rate of kidney discard, disturb the short-term function of allografts, and increase the risk of urolithiasis in recipients. Further research with a long-term study is needed to verify the long-term outcome of kidney transplantation using cadaveric kidney allografts with nephrolithiasis.
9.A comparative study on the difference coefficients of DRG payment in various cities in Zhejiang province
Yufei JIANG ; Jiayi GUO ; Jianlie YUAN ; Minhui XU ; Hongyi ZHANG ; Guobin HE
Chinese Journal of Hospital Administration 2022;38(6):443-447
In order to compare the setting of difference coefficients in DRG point payment in different cities in Zhejiang province, the implementation rules of DRG point payment issued by 11 cities in Zhejiang province were comprehensively analyzed. It was found that the difference coefficients in different cities could be divided into three categories, including hospital coefficients alone, hospital coefficients and grade coefficients weighted, and weighted by hospital coefficients, grade coefficients, personal burden levels, case mix indexes, and head-to-time ratio. Its setting differences included four aspects: connotation composition, weight distribution, threshold value, and classification of medical institutions. The authors suggested that the adjustment cycle should be set scientifically to dynamically adjust the difference coefficient, and the scientific setting of the difference coefficient should be promoted through provincial coordination.
10. Research Progress of TREM-1 in Immune-related Intestinal Diseases
Yingjie SI ; Jiang LIN ; Hongyi HU
Chinese Journal of Gastroenterology 2021;26(1):43-47
Triggering receptor expressed on myeloid cells-1 (TREM-1), which plays a major role in the pathogenesis of infectious and non-infectious inflammation, is an important inflammation regulator. This article reviewed the structure and forms of TREM-1, mechanism on regulation of inflammation and relationship with immune-related intestinal diseases, thereby to investigate the role and potential value of TREM-1 on diagnosis, prognosis prediction and treatment target in immune-related intestinal diseases.

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