1.Analyses of T lymphocyte subset levels and viral loads in human immunodeficiency virus antibody-confirmed positive cases in Suzhou from 2021 to 2024
Runfang TIAN ; Qiang SHEN ; Xuerong YA ; Yue DAI ; Qian GAO
Shanghai Journal of Preventive Medicine 2026;38(3):210-215
ObjectiveTo investigate the T lymphocyte subset levels and viral loads in newly human immunodeficiency virus (HIV) antibody-confirmed positive cases in Suzhou (2021‒2024), and to analyze potential influencing factors by integrating their demographic characteristics, immune status, and viral replication patterns, thereby providing evidence for HIV/acquired immune deficiency syndrome (AIDS) prevention and control. MethodsPeripheral whole blood samples were collected from newly confirmed HIV-positive cases in Suzhou from 2021 to 2024. T lymphocyte subset analysis and viral load testing were performed, and influencing factors were identified in combination with demographic characteristics. Logistic regression models were employed to identify factors associated with CD4+T lymphocyte counts ≤350 cells·μL-1, and Spearman’s rank correlation test was used to analyze the correlation between logarithmic value of viral load and CD4+/CD8+ ratio. ResultsAmong the 3 022 confirmed HIV-positive samples, the median CD4+T lymphocyte count was 298.00 cells·μL-1, with 882 cases (29.19%) showing CD4+ T lymphocyte counts <200 cells·μL-1. The median CD8+T lymphocyte count was 1 011.00 cells·μL-1. The median CD4+/CD8+ ratio was 0.28, with 32.46% of cases exhibiting CD4+/CD8+ ratios <0.20, and there were statistically significant differences in CD4+/CD8+ ratio among different genders, age groups, marital status, and sample sources (all P<0.05). Multivariate logistic regression analyses indicated that individuals aged ≥20 years, those who were divorced or widowed, and cases identified through medical institutions had a significantly higher proportion of CD4+T lymphocyte counts ≤350 cells·µL⁻¹ compared to those aged <20 years, unmarried individuals, and cases sourced from voluntary counseling and testing (VCT) clinics, respectively. The mean logarithmic value of viral load was (4.29±1.15) copies·mL-1. The logarithmic value of viral load demonstrated a significantly negative correlation with both CD4+/CD8+ ratio (r=-0.43, P<0.001) and CD4+T lymphocyte count (r=-0.37, P<0.001). ConclusionA substantial proportion of newly diagnosed HIV/AIDS cases in Suzhou are late presenters with high viral load levels. Targeted interventions should prioritize high-risk populations through enhanced active surveillance and the implementation of combined T lymphocyte subsets analysis and viral load testing, which can enable earlier case-finding and timely antiretroviral therapy initiation.
2.Neuroelectromagnetic Activities Across Temporal Scales
Zhuo-Qun SHEN ; Xiao-Fei XU ; Yan-Qing WANG ; Jing-Xin LI ; Lan TIAN ; Wei GUO ; Jing-Jing XU
Progress in Biochemistry and Biophysics 2026;53(6):1541-1560
Although global brain science research has progressed rapidly in recent decades, several fundamental questions in neuroscience remain unresolved. In particular, the physical mechanism underlying neural signal transmission remains controversial, and the carriers responsible for neural information storage and retrieval have not yet been fully clarified. These unresolved issues motivate us to re-examine the processes of neural information generation, transmission, integration, storage, and retrieval from multiple perspectives. A key observation is that neural electromagnetic activities are closely associated with time. Their duration, temporal structure, and dynamic evolution play crucial roles in neural information processing. In this work, we analyze neural electromagnetic activities from the perspective of temporal scales (referred to here as the “time course”). By reviewing and integrating findings from previous studies, we examine the characteristic time requirements and dynamic features of neural processes occurring at different stages of information processing. These stages include neural signal generation, signal transmission along axons, synaptic integration, synaptic plasticity, and memory formation and retrieval. Based on this temporal analysis, we outline a framework describing neural electromagnetic activities across a wide range of time scales, spanning from microseconds to minutes, hours, or even longer periods associated with long-term memory, which suggests that neural information processing involves multiple physical processes operating at different time levels. Rapid electromagnetic events may occur on microsecond scales, whereas electrophysiological phenomena such as action potentials typically last on the order of milliseconds. Longer time scales are associated with synaptic plasticity and memory-related processes. From this perspective, we propose that the physical carrier of neural information may be transient electromagnetic pulses with durations on the microsecond scale. In this framework, action potentials can be interpreted as the macroscopic electrophysiological manifestation of underlying electromagnetic processes triggered by ionic currents across neuronal membranes. Rather than being the fundamental neural signal itself, the action potential may represent a measurable membrane-level response associated with the successful activation of these electromagnetic events. Moreover, we discuss a possible mechanism for long-term memory storage. Considering the apparent temporal contradiction between the millisecond-scale excitation of neurons and the long-term persistence of memories, we believe that long-term memory information may be stored within neural network topologies formed by electrical synapse coupling. Such structures, referred to as electrically coupled memory networks (ECMNs), may enable neurons within the same network to respond rapidly and synchronously to stimuli, thereby facilitating efficient memory retrieval. Overall, this study emphasizes the importance of considering the temporal organization of neural electromagnetic activities when interpreting neural signaling mechanisms. It may provide new insights into the physical nature of neural information carriers and the mechanisms of memory storage and retrieval. Furthermore, highlighting the potential role of electromagnetic interactions in neural activity may contribute to the development of new theoretical frameworks and experimental approaches in neuroscience. Such perspectives may also offer valuable references for future research on neural coding, brain function mechanisms, and neuromodulation technologies.
3.5G remote robot-assisted thoracoscopic lobectomy/segmentectomy for ten patients
Fan SHEN ; Jia HUANG ; Yu TIAN ; Hanbo PAN ; Jiantao LI ; Long JIANG ; Hong GUO ; Bentong YU ; Qingquan LUO
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2026;33(06):908-912
Objective To explore the safety and feasibility of 5G remote robot-assisted thoracoscopic anatomic lobectomy and segmentectomy. Methods A retrospective analysis was conducted on patients who underwent 5G remote robot-assisted thoracoscopic anatomic lobectomy or segmentectomy between July and September 2024. The surgeries were performed collaboratively by Shanghai Chest Hospital, Affiliated Hospital of Yangzhou University, and The First Affiliated Hospital of Nanchang University. Perioperative outcomes were recorded and analyzed. Results Ten patients were included, comprising 4 anatomic lobectomies and 6 segmentectomies. The median age was 61.0 (56.0, 72.0) years. The median intraoperative bi-directional network latency was 52.5 (39.0, 54.0) ms. There were no instances of network interruption, robot-related adverse events, or conversions to open thoracotomy. The median postoperative chest tube drainage volume was 500.0 (375.0, 600.0) mL, and the median hospital stay was 5.5 (4.0, 6.0) days. No complications of Clavien-Dindo grade Ⅱor higher occurred. All patients were recurrence-free and alive during the 6-month postoperative follow-up period. Conclusion 5G remote robot-assisted thoracoscopic surgery demonstrates high safety and operational stability. This technology shows promising potential for clinical application and is worthy of further development and utilization.
4.Pathogen detection and genetic characteristic analyses of hand-foot-and-mouth disease in Dehong Prefecture of Yunnan Province in 2023
Zhuoya GAO ; Jiangli ZHU ; Dingfu LUO ; Bingjun TIAN ; Kang YANG ; Zengjiao DUAN ; Runbo ZHANG ; Yinghao CHEN ; Zhuo SHEN
Shanghai Journal of Preventive Medicine 2026;38(6):446-452
ObjectiveTo genotype the specimens from hand-foot-and-mouth disease (HFMD) cases in Dehong Prefecture, Yunnan Province in 2023 by gene sequencing, and to analyze the genetic characteristics of Coxsackievirus A4 (CVA4), CVA6, CVA10, CVA16 and enterovirus A71 (EV-A71), so as to clarify the serotypes of enteroviruses causing endemic HFMD and the genotype composition of CVA4, CVA6, CVA10, CVA16 and EV-A71 prevalent in HFMD, and to provide baseline genotype data for monitoring the dynamic changes of the five virus genotypes. MethodsStool specimens from HFMD cases in Dehong Prefecture in 2023 that tested positive for EV-A71, CVA16 and other enteroviruses by real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR) were first subjected to gene sequencing and typing of the VP4/VP2 junction region to determine the viral types. Subsequently, the complete VP1 gene of each virus was amplified in two segments using group-specific VP1 gene primers corresponding to enterovirus groups (i.e., enterovirus group A, B, and C) and sequenced (group A virus: primers 486/488 and 487/489, group B virus: primers 490/492 and 491/493, group C virus: primers 494/496 and 495/497). The representative reference sequences of VP1 genes for CVA4, CVA6, CVA10, CVA16 and EV-A71 were downloaded from the literature, and the VP1 gene phylogenetic tree was constructed using MEGA 6.0 software for genetic characterization. ResultsA total of 256 stool specimens were collected from HFMD cases in Dehong Prefecture in 2023, of which 94 tested positive for nucleic acid by RT-qPCR, yielding a positive rate of 36.72%. Of the 94 positive specimens, 83 were identified as group A viruses, and were classified into 5 serotypes (17 strains of CVA4, 3 of CVA6, 6 of CVA10, 49 of CVA16, and 8 of EV-A71). Nine strains were group B viruses, comprising 2 serotypes: 2 strains of echovirus type 3 (E3) and 7 strains of Coxsackievirus B type 5 (CVB5). The remaining 2 strains were group C viruses, both identified as poliovirus type 3 (PV3). Genetic analyses of the VP1 region showed that all 17 CVA4 strains were identified as subgenotype C2, all 3 CVA6 strains as subgenotype D3a, all 6 CVA10 strains as genotype C. Among the 49 CVA16 strains, 46 were identified as subgenotype B1a and 3 as subgenotype B1b, and all 8 EV-A71 strains were identified as subgenotype C4a. ConclusionIn 2023, group A viruses dominated the pathogenic spectrum of HFMD in Dehong Prefecture. Among them, CVA16 had the highest positivity rate. Genetic characteristic analyses showed that CVA4, CVA6, CVA10 and EV-A71 were each composed of a single genotype (subgenotype), while CVA16 was composed of two subgenotypes (B1a and B1b), with B1a being the predominant one. It is recommended that molecular epidemiological surveillance of HFMD pathogens, particularly group A viruses, be continuously strengthened in Dehong Prefecture.
5.Changes in health status and management strategies for workers in a chemical enterprise under low-level multiple occupational exposure
Xueting WANG ; Jiming ZHANG ; Yulai TIAN ; Zhiping DUAN ; Wenjie LI ; Chaoye SHEN ; Dasheng LU ; Zhijun ZHOU
Journal of Environmental and Occupational Medicine 2026;43(6):693-701
Background Long-term occupational health surveillance facilitates the identification of chronic health risks arising from occupational hazard exposures. However, under low-level exposure conditions in chemical enterprises, traditional workplace-centered risk assessment models are insufficient to fully explain the observed health effects among workers, highlighting the need for individual-focused health management strategies that focus on the worker. Objective To characterize long-term health trends among workers in a chemical enterprise and examine the limitations of workplace hazard monitoring and health surveillance under low-level multiple exposure scenarios, thereby providing a scientific basis for more comprehensive worker health protection measures. Methods We analyzed 972 occupational health examination records collected over a 15-year period (2010–2024) from a chemical enterprise, integrating these with enterprise hazard monitoring reports and workshop air monitoring of volatile organic compounds (VOCs). The annual counts and prevalences of abnormalities in liver function tests, metabolic syndrome-related indicators, and liver imaging were summarized. Temporal trends were evaluated using the Cochran-Armitage trend test. Time-related changes in abnormal health indicators among active workers were evaluated by generalized linear mixed-effects models (GLMMs), adjusting for age and sex. Individual longitudinal profiles were described for nine workers with continuous 15-year records. In addition, paired comparisons of health outcomes were conducted for 81 workers with both pre-employment and periodic examinations. Results Workplace hazard monitoring indicated that airborne concentrations of major occupational contaminants including VOCs, acids and bases, dust, and physical factors were below national occupational exposure limits. However, 62 VOC species—including chlorobenzene, chloromethane, and cyclohexane—were detected in workshop air, suggesting complex mixed organic solvent exposure. From 2010 to 2015, occupational health examination records were primarily based on physicians’ qualitative assessment, yielding generally low abnormality detection rates. During 2016–2024, data collection was complete, and the prevalences of abnormalities in liver function, metabolic syndrome-related indicators, and liver imaging among active workers remained relatively high. Trend analysis indicated that only the abnormality rates of total bilirubin (TBIL) and hypertension showed statistically significant temporal trends; other indicators exhibited no significant linear changes despite high prevalences. After adjusting for age and sex, the GLMMs showed that the abnormality rates of aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), TBIL, and hypertension decreased over time, whereas those of total cholesterol, triglycerides, and fatty liver increased. In a subgroup of 9 workers with continuous 15-year follow-up data, the cumulative number of abnormal health indicators increased in several individuals after 2016. Among the 81 workers with both pre-employment and periodic records, abnormalities in total cholesterol, triglycerides, body mass index, and fatty liver were significantly more prevalent after employment over time, whereas changes in liver function enzymes were not statistically significant. Conclusion With increasing age, workers exhibit a gradual deterioration in liver function and metabolic-related health indicators, reaching abnormality rates comparable to those reported in the general population. These findings suggest that both workplace-related and non-occupational factors jointly contribute to the observed health changes. Consequently, occupational health management should shift towards an "individual-centered" approach. Enhancing workers' health literacy, strengthening workplace health promotion, and extending occupational health services beyond the workplace are essential to comprehensively protect workers' health.
6.Effect of anterior seat inclination on sit-to-stand ability in patients with stroke and related brain network
Xiaohua SHEN ; Fangyuan CHEN ; Jifeng RONG ; Biaoqin RAO ; Lingxuan KONG ; Wei TIAN ; Zhiqun CHEN ; Li LI
Chinese Journal of Rehabilitation Theory and Practice 2026;32(9):1061-1067
ObjectiveTo observe the clinical effect of anterior seat inclination on sit-to-stand (STS) ability and balance function in patients with stroke, as well as brain functional connectivity based on functional near-infrared spectroscopy (fNIRS). MethodsFrom January, 2024 to December, 2025, 43 patients with stroke were randomly divided into control group (n = 21) and experimental group (n = 22). The control group received conventional rehabilitation combined with STS training on a flat seat, while the experimental group received conventional rehabilitation plus STS training with a 20° anterior seat inclination, for two weeks. Five-times sit-to-stand test (FTSST) and Berg Balance Scale (BBS) were assessed before and after training. fNIRS was used to detect changes in cerebral blood oxygenation in the prefrontal cortex (PFC), primary motor cortex (M1), primary somatosensory cortex (S1) and premotor cortex (PMC), and to analyze functional connectivity strength. ResultsAfter training, FTSST time shortened in both groups (t > 3.469, P < 0.01), and was shorter in the experimental group than in the control group (t = -2.065, P < 0.05); BBS scores increased in both groups (|Z| > 4.019, P < 0.01), and was higher in the experimental group than in the control group (Z = -2.250, P < 0.05). fNIRS showed that after training, the functional connectivity strength between the left M1 and the right PFC increased, as well as between the left M1 and the right S1 in the experimental group (t > 3.311, P < 0.05). ConclusionSTS training with anterior seat inclination can enhance functional connectivity in relevant brain regions, which may contribute to improvements of STS ability and balance function in patients with stroke.
7.Relationship between levels of novel inflammatory indicators and aggressivity in patients with first-episode and recurrent schizophrenia
Ying'ao CUI ; Cheng YANG ; Yinghan TIAN ; Qingqing SHEN ; Huanzhong LIU
Sichuan Mental Health 2025;38(1):28-33
BackgroundAggressive behavior in schizophrenic patients could result in legal disputes and public safety concerns. In patients with illness episodes of different numbers, there may exist differences in the association between levels of novel inflammatory indicators and aggressivity. ObjectiveTo investigate the differences in the correlation between levels of novel inflammatory indicators and aggressivity in patients with first-episode and recurrent schizophrenia, in order to search for inflammatory biomarkers to assess aggression level in schizophrenic patients. MethodsA total of 168 schizophrenic patients were selected as subjects, who were hospitalized for acute disease onset in Chaohu Hospital of Anhui Medical University from October 2022 to April 2024 as well as met the diagnostic criteria of Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5). Patients were divided into first-episode group (n=58) and recurrent group (n=110). Meanwhile, 110 healthy controls from community who matched in age and gender with the patient group were recruited. All patients were evaluated with Modified Overt Aggression Scale (MOAS) and Positive and Negative Syndrome Scale (PANSS). All subjects went through examination of the levels of novel inflammatory indicators, including neutrophil/lymphocyte ratio (NLR), monocyte/lymphocyte ratio (MLR), platelet/lymphocyte ratio (PLR), neutrophil/high-density lipoprotein ratio (NHR), monocyte/high-density lipoprotein ratio (MHR) and platelet/high-density lipoprotein ratio (PHR). Spearman correlation analysis was adopted to investigate the correlation between levels of novel inflammatory indicators and the total score of MOAS in patients with first-episode and recurrent schizophrenia. ResultsThe levels of NLR, MLR, PLR, NHR, MHR and PHR in first-episode group were higher than those in control group (adjusted P<0.01). The levels of NLR, MLR, NHR, MHR and PHR in recurrent group were higher than those in control group (adjusted P<0.01). No significant difference was observed in the comparison in the levels of six novel inflammatory indicators between first-episode group and recurrent group (adjusted P>0.05). Spearman correlation analysis showed, the MOAS total score of recurrent group was positively correlated with the levels of NLR, MLR and PLR (r=0.234, 0.192, 0.243, P<0.05). There was no statistical significance in the correlation between MOAS total score and levels of six novel inflammatory indicators in first-episode group (P>0.05). ConclusionAmong patients with first-episode and recurrent schizophrenia, the correlation between levels of novel inflammatory indicators and aggressivity could differ. NLR, MLR and PLR might be the biomarkers for assessing aggression level in recurrent schizophrenic patients. [Funded by Anhui Provincial Natural Science Foundation (number, 2108085MH275)]
8.Predictive value of bpMRI for pelvic lymph node metastasis in prostate cancer patients with PSA≤20 μg/L.
Lai DONG ; Rong-Jie SHI ; Jin-Wei SHANG ; Zhi-Yi SHEN ; Kai-Yu ZHANG ; Cheng-Long ZHANG ; Bin YANG ; Tian-Bao HUANG ; Ya-Min WANG ; Rui-Zhe ZHAO ; Wei XIA ; Shang-Qian WANG ; Gong CHENG ; Li-Xin HUA
National Journal of Andrology 2025;31(5):426-431
Objective: The aim of this study is to explore the predictive value of biparametric magnetic resonance imaging(bpMRI)for pelvic lymph node metastasis in prostate cancer patients with PSA≤20 μg/L and establish a nomogram. Methods: The imaging data and clinical data of 363 patients undergoing radical prostatectomy and pelvic lymph node dissection in the First Affiliated Hospital of Nanjing Medical University from July 2018 to December 2023 were retrospectively analyzed. Univariate analysis and multivariate logistic regression were used to screen independent risk factors for pelvic lymph node metastasis in prostate cancer, and a nomogram of the clinical prediction model was established. Calibration curves were drawn to evaluate the accuracy of the model. Results: Multivariate logistic regression analysis showed extrocapusular extension (OR=8.08,95%CI=2.62-24.97, P<0.01), enlargement of pelvic lymph nodes (OR=4.45,95%CI=1.16-17.11,P=0.030), and biopsy ISUP grade(OR=1.97,95%CI=1.12-3.46, P=0.018)were independent risk factors for pelvic lymph node metastasis. The C-index of the prediction model was 0.834, which indicated that the model had a good prediction ability. The actual value of the model calibration curve and the prediction probability of the model fitted well, indicating that the model had a good accuracy. Further analysis of DCA curve showed that the model had good clinical application value when the risk threshold ranged from 0.05 to 0.70.Conclusion: For prostate cancer patients with PSA≤20 μg/L, bpMRI has a good predictive value for the pelvic lymph node metastasis of prostate cancer with extrocapusular extension, enlargement of pelvic lymph nodes and ISUP grade≥4.
Humans
;
Male
;
Prostatic Neoplasms/diagnostic imaging*
;
Lymphatic Metastasis
;
Retrospective Studies
;
Nomograms
;
Prostate-Specific Antigen/blood*
;
Lymph Nodes/pathology*
;
Pelvis
;
Predictive Value of Tests
;
Prostatectomy
;
Lymph Node Excision
;
Risk Factors
;
Magnetic Resonance Imaging
;
Logistic Models
;
Middle Aged
;
Aged
9.Bear Bile Powder Ameliorates LPS-Induced Acute Lung Injury by Inhibiting CD14 Pathway and Improving Intestinal Flora: Exploration of "Fei (Lung)-Dachang (Large Intestine) Interaction" Theory.
Long CHENG ; Hui-Ling TIAN ; Hong-Yuan LEI ; Ying-Zhou WANG ; Ma-Jing JIAO ; Yun-Hui LIANG ; Zhi-Zheng WU ; Xu-Kun DENG ; Yong-Shen REN
Chinese journal of integrative medicine 2025;31(9):821-829
OBJECTIVE:
To explore the effect of bear bile powder (BBP) on acute lung injury (ALI) and the underlying mechanism.
METHODS:
The chemical constituents of BBP were analyzed by ultra-high-pressure liquid chromatography-mass spectrometry (UPLC-MS). After 7 days of adaptive feeding, 50 mice were randomly divided into 5 groups by a random number table (n=10): normal control (NC), lipopolysaccharide (LPS), dexamethasone (Dex), low-, and high-dose BBP groups. The dosing cycle was 9 days. On the 12th and 14th days, 20 µL of Staphylococcus aureus solution (bacterial concentration of 1 × 10-7 CFU/mL) was given by nasal drip after 1 h of intragastric administration, and the mice in the NC group was given the same dose of phosphated buffered saline (PBS) solution. On the 16th day, after 1 h intragastric administration, 100 µL of LPS solution (1 mg/mL) was given by tracheal intubation, and the same dose of PBS solution was given to the NC group. Lung tissue was obtained to measure the myeloperoxidase (MPO) activity, the lung wet/dry weight ratio and expressions of CD14 and other related proteins. The lower lobe of the right lung was obtained for pathological examination. The concentrations of inflammatory cytokines including interleukin (IL)-6, tumour necrosis factor α (TNF-α ) and IL-1β in the bronchoalveolar lavage fluid (BALF) were detected by enzyme linked immunosorbent assay, and the number of neutrophils was counted. The colonic contents of the mice were analyzed by 16 sRNA technique and the contents of short-chain fatty acids (SCFAs) were measured by gas chromatograph-mass spectrometer (GC-MS).
RESULTS:
UPLC-MS revealed that the chemical components of BBP samples were mainly tauroursodeoxycholic acid and taurochenodeoxycholic acid sodium salt. BBP reduced the activity of MPO, concentrations of inflammatory cytokines, and inhibited the expression of CD14 protein, thus suppressing the activation of NF-κB pathway (P<0.05). The lung histopathological results indicated that BBP significantly reduced the degree of neutrophil infiltration, cell shedding, necrosis, and alveolar cavity depression. Moreover, BBP effectively regulated the composition of the intestinal microflora and increased the production of SCFAs, which contributed to its treatment effect (P<0.05).
CONCLUSIONS
BBP alleviates lung injury in ALI mouse through inhibiting activation of NF-κB pathway and decreasing expression of CD14 protein. BBP may promote recovery of ALI by improving the structure of intestinal flora and enhancing metabolic function of intestinal flora.
Animals
;
Acute Lung Injury/pathology*
;
Lipopolysaccharides
;
Ursidae
;
Gastrointestinal Microbiome/drug effects*
;
Bile/chemistry*
;
Lipopolysaccharide Receptors/metabolism*
;
Powders
;
Male
;
Lung/drug effects*
;
Mice
;
Peroxidase/metabolism*
;
Signal Transduction/drug effects*
;
Cytokines/metabolism*
10.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.

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