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.Effect of radiofrequency radiation from 5G mobile phone on blood-brain barrier in mice
Guiqiang ZHOU ; Yizhe XUE ; Zhaowen ZHANG ; Tongzhou QIN ; Ling GUO ; Panpan LAI ; Peng GAO ; Xing WANG ; Zhifei HUANG ; Yuhang ZANG ; Yuntao JING ; Guirong DING
Chinese Journal of Radiological Medicine and Protection 2023;43(3):176-181
Objective:To investigate the effect of radiofrequency radiation (RF) from 5G mobile phone communication frequency bands (3.5 GHz and 4.9 GHz) on the permeability of the blood-brain barrier (BBB) in mice.Methods:A total of 24 healthy adult male C57BL/6 mice (6-8 weeks old) were randomly divided into Sham, 3.5 GHz RF and 4.9 GHz RF groups, and 8 mice in each group. Mice in the RF groups were systemically exposed to 5G cell phone radiation for consecutive 35 d(1 h/d) with 50 W/m 2 power density. The BBB permeability of mice was detected by Evans Blue (EB) fluorescence experiment. The expression levels of the BBB tight junction-related proteins (ZO-1, occludin and claudin-11) and the gap junction-related protein Connexin 43 were determined by Western blot. Results:The number of spots, fluorescence intensity and comprehensive score of EB were significantly increased in 3.5 GHz RF group and 4.9 GHz RF group compared with the Sham group ( t=12.98, 17.82, P<0.001). Compared with the Sham group, the content of S100B in mouse serum was significantly increased in 3.5 GHz RF group and 4.9 GHz RF group ( t=19.34, 14.68, P<0.001). The BBB permeability was increased in the RF group. The expression level of occludin protein was significantly reduced in the 3.5 GHz RF group ( t=-3.13, P<0.05), and this decrease was much profound in the 4.9 GHz RF group ( t=-6.55, P<0.01). But the protein levels of ZO-1, Claudin-11 and Connexin 43 in the cerebral cortex of the RF groups had no significantly difference in comparison with the Sham group( P>0.05). Conclusions:The continuous exposure of mobile phone RF at 3.5 GHz or 4.9 GHz for 35 d (1 h/d) induces an increase of BBB permeability in the mouse cerebral cortex, perhaps by reducing the expression of occludin protein.
3.Recommendations for prescription review of commonly used anti-seizure medications in treatment of children with epilepsy
Qianqian QIN ; Qian DING ; Xiaoling LIU ; Heping CAI ; Zebin CHEN ; Lina HAO ; Liang HUANG ; Yuntao JIA ; Lingyan JIAN ; Zhong LI ; Hua LIANG ; Maochang LIU ; Qinghong LU ; Xiaolan MO ; Jing MIAO ; Yanli REN ; Huajun SUN ; Yanyan SUN ; Jing XU ; Meixing YAN ; Li YANG ; Shengnan ZHANG ; Shunguo ZHANG ; Xin ZHAO ; Jie DENG ; Fang FANG ; Li GAO ; Hong HAN ; Shaoping HUANG ; Li JIANG ; Baomin LI ; Jianmin LIANG ; Jianxiang LIAO ; Zhisheng LIU ; Rong LUO ; Jing PENG ; Dan SUN ; Hua WANG ; Ye WU ; Jian YANG ; Yuqin ZHANG ; Jianmin ZHONG ; Shuizhen ZHOU ; Liping ZOU ; Yuwu JIANG ; Xiaoling WANG
Chinese Journal of Applied Clinical Pediatrics 2023;38(10):740-748
Anti-seizure medications (ASMs) are the main therapy for epilepsy.There are many kinds of ASMs with complex mechanism of action, so it is difficult for pharmacists to examine prescriptions.This paper put forward some suggestions on the indications, dosage forms/routes of administration, appropriateness of usage and dosage, combined medication and drug interaction, long-term prescription review, individual differences in pathophysiology of children, and drug selection when complicated with common epilepsy, for the reference of doctors and pharmacists.
4.Effectiveness of Longji Daoyin exercise on adolescents of mild idiopathic scoliosis
LIU Lu, ZHANG Wei, HU Zengping, GAO Yang, GU Chuanchuan, YAN Yuntao, DU Shuangqing
Chinese Journal of School Health 2023;44(1):119-122
Objective:
To explore the effectiveness of spinal guidance exercise on adolescents of mild idiopathic scoliosis, so as to provide an experimental reference and method for promoting adolescents spinal health.
Methods:
From the scoliosis screening, 96 children who met the diagnostic criteria were selected in June 2021, and were divided into the experimental group and the control group, with 48 cases in each group. The experimental group received a 12 week Longji Daoyin exercise training, and the control group received health education, observation and monitoring. Before and after the experiment, the axial trunk rotation (ATR) and scoliosis Cobb angle of the two groups were tested respectively, and the subjective sensation of the patients was measured by Scoliosis Research Society-22(SRS-22) questionnaire.
Results:
After 12 weeks, the ATR and Cobb angles of the experimental group decreased [( 5.02± 2.85,7.59±3.94)°],compared to (7.08±2.84)° and (15.84±2.00)° before intervention( t =14.02, 17.09, P < 0.01 ). Scores of functional activity, self image and mental health in the SRS-22 score increased from (4.65±0.14)(3.49±0.21) and (3.99±0.17) to(4.77±0.14)(4.62±0.13)(4.42±0.13)( t =-4.86,-39.12,-13.92, P <0.01 ). The ATR and Cobb angles of the control group increased from (6.94±2.15)° and (15.82±1.76)° to (8.25±2.49)° and (18.63±3.12)°( t =7.44,8.99, P <0.01), and the scores of self image and mental health in the SRS-22 score decreased from (3.49±0.19) and (4.00±0.15) to (3.44±0.18) and (3.94±0.14)( t =-3.74,-4.39, P <0.05).
Conclusion
Early adolescent idiopathic scoliosis is easy to aggravate during the observation period. Longji Daoyin exercise is of preventive and therapeutic significance.
5.Recommendations for prescription review of antipyretic-analgesics in symptomatic treatment of children with fever
Xiaohui LIU ; Xing JI ; Lihua HU ; Yuntao JIA ; Huajun SUN ; Qinghong LU ; Shengnan ZHANG ; Ruiling ZHAO ; Shunguo ZHANG ; Yanyan SUN ; Meixing YAN ; Lina HAO ; Heping CAI ; Jing XU ; Zengyan ZHU ; Hua XU ; Jing MIAO ; Xiaotong LU ; Zebin CHEN ; Hua CHENG ; Yunzhu LIN ; Ruijie CHEN ; Xin ZHAO ; Zhenguo LIU ; Junli ZHANG ; Yuwu JIANG ; Chaomin WAN ; Gen LU ; Hengmiao GAO ; Ju YIN ; Kunling SHEN ; Baoping XU ; Xiaoling WANG
Chinese Journal of Applied Clinical Pediatrics 2022;37(9):653-659
Antipyretic-analgesics are currently one of the most prescribed drugs in children.The clinical application of antipyretic-analgesics for children in our country still have irrational phenomenon, which affects the therapeutic effect and even poses hidden dangers to the safety of children.In this paper, suggestions were put forward from the indications, dosage form/route, dosage suitability, pathophysiological characteristics of children with individual differences and drug interactions in the symptomatic treatment of febrile children, so as to provide reference for the general pharmacists when conducting prescription review.
6.Evaluation of safety of two inactivated COVID-19 vaccines in a large-scale emergency use
Zhongnan YANG ; Yunya ZHAO ; Lu LI ; Huidi GAO ; Qi CAI ; Xiaoxia SUN ; Fusheng ZHANG ; Jinfeng SU ; Yinan ZHANG ; Xiang SHU ; Xuewei WANG ; Yunkai YANG ; Yuntao ZHANG ; Song ZHOU ; Xiaoming YANG
Chinese Journal of Epidemiology 2021;42(6):977-982
Objective:To evaluate the safety of two inactivated COVID-19 vaccines in a large-scale emergency use.Methods:Based on the "Vaccination Information Collection System", the incidence data of adverse reactions in the population vaccinated with the inactivated COVID-19 vaccines developed by Beijing Institute of Biological Products Co., Ltd and Wuhan Institute of Biological Products Co., Ltd, respectively, in emergency use were collected, and the relevant information were analyzed with descriptive epidemiological and statistical methods.Results:By December 1, 2020, the vaccination information of 519 543 individuals had been collected. The overall incidence rate of adverse reactions was 1.06%, the incidence rate of systemic adverse reactions was 0.69% and the incidence rate of local adverse reactions was 0.37%. The main systemic adverse reactions included fatigue, headache, fever, cough and loss of appetite with the incidence rates of 0.21%, 0.14%, 0.06%, 0.05% and 0.05%, respectively; the main local adverse reactions were injection site pain and injection site swelling with the incidence rates of 0.24% and 0.05%, respectively.Conclusion:The two inactivated COVID-19 vaccines by Beijing Institute of Biological Products Co., Ltd and Wuhan Institute of Biological Products Co., Ltd showed that in the large-scale emergency use, the incidence rate of general reactions was low and no serious adverse reactions were observed after the vaccinations, demonstrating that the vaccines have good safety.
7. Expression of galectin-1 in Chinese laryngeal squamous cell carcinoma patients and its clinical significance
Wei WEI ; Yuntao SONG ; Guohui XU ; Yuezhang WU ; Liping GAO ; Kang XIAO ; Qi SHI
Chinese Journal of Experimental and Clinical Virology 2019;33(6):566-569
Objective:
To observe the expression and clinical significance of galectin-1 in Chinese laryngeal squamous cell carcinoma patients.
Methods:
Immunohistochemical technique was used to test the galecin-1 protein expression in the 50 laryngeal squamous cell carcinoma patients and Western blot method was used to test the galecin-1 protein expression in the 3 of the patients. SAS 9.4 software was used to analyze the relationship between the galectin-1 protein and the clinical degrees, pathological grades and lymph node metastasis in all the cases.
Results:
In the 50 laryngeal squamous cell carcinoma patients, the positive rate of galectin-1 protein was 74% (37/50). The expression of galectin-1 protein was correlated with the severity of clinical staging, pathological differentiation and lymph node metastasis.
Conclusions
High expression of galectin protein related with the occurrence and development of head and neck squamous cell carcinomas.
8.One-stage anterior debridement combined with posterior pedicle screw fixation to treat cervical vertebral space infection
Ye LI ; Qingsan ZHU ; Zhongwen GAO ; Jingchen LIU ; Yuntao WU ; Haifeng HU ; Hanlei ZHANG ; Yunlong ZOU ; Rui GU ; Jing CHEN
Chinese Journal of Orthopaedics 2018;38(13):769-777
Objective To evaluate the efficacy of one stage anterior debridement combined with posterior pedicle screw fixation in the treatment of cervical intervertebral space infection.Methods From June 2010 to June 2016,28 cases were fixed by anterior debridement combined with the posterior vertebral pedicle screws for the cervical intervertebral space infection,19 males and 9 females.The average age was 45-74 years (58±14.5 years old).21 cases (75%) were spontaneous infection,of which 6 cases were diabetes mellitus,15 cases were over 60 years old.The remaining 7 cases (25%) were intervertebral space infection after radiofrequency ablation of the cervical spine.All patients were excluded from tuberculosis and Brucella infection.All patients underwent hematological examination,with emphasis on WBC,ESP and CRP.All patients received JOA score before operation,applied antibiotic according to blood culture and drug sensitive test.All patients underwent one stage anterior debridement combined with posterior pedicle screw fixation,and the operative time and bleeding volume were recorded.After the operation,intravenous antibiotic therapy was continued,and the application of antibiotics was guided according to the results of ESP and CRP,and the time for the application of antibiotics was recorded.Follow up was performed at 3 months,6 months and 1 years after operation respectively.The JOA score and postoperative cervical lordosis Cobb angle were recorded.Results All operations were successfully completed in this group.The operation time was 130-225 min,with an average of 145.5±12.7 min.The intraoperative blood loss was 40-100 ml,with an average of 67±35.2 ml.The incision was healed in one stage.The time of application of antibiotics in 28 patients was 21-87 days,with an average of 30.8±8.7 days.The longest application time of antibiotics was 87 days,and no relapse was found during follow-up.The postoperative JOA score increased from 11.3± 1.2 to three months 14.9 ± 1.96 postoperatively and 6 months 15.1 ± 1.55 and 1 years 16.5±0.48 after operation.The JOA score was significantly higher than that before operation.No significant loss and change of the Cobb angle in the cervical spine surgery were found.All cases had good bone graft fusion at 1 years.Conclusion One stage anterior debridement combined with posterior pedicle screw fixation is a safe and effective method for the treatment of cervical vertebra instability and nerve function injury caused by cervical intervertebral space infection.It provides a new way for the treatment of cervical intervertebral space infection.
9.Automatic detection and classification of atrial fibrillation using RR intervals and multi-eigenvalue.
Zhibo CHEN ; Jian LI ; Zhi LI ; Yuntao PENG ; Xingjiao GAO
Journal of Biomedical Engineering 2018;35(4):550-556
Atrial fibrillation (AF) is a common arrhythmia disease. Detection of atrial fibrillation based on electrocardiogram (ECG) is of great significance for clinical diagnosis. Due to the non-linearity and complexity of ECG signals, the procedure to manually diagnose the ECG signals takes a lot of time and is prone to errors. In order to overcome the above problems, a feature extraction method based on RR interval is proposed in this paper. The discrete degree of RR interval is described with the robust coefficient of variation (RCV), the distribution shape of RR interval is described with the skewness parameter (SKP), and the complexity of RR interval is described with the Lempel-Ziv complexity (LZC). Finally, the feature vectors of RCV, SKP, and LZC are input into the support vector machine (SVM) classifier model to achieve automatic classification and detection of atrial fibrillation. To verify the validity and practicability of the proposed method, the MIT-BIH atrial fibrillation database was used to verify the data. The final classification results show that the sensitivity is 95.81%, the specificity is 96.48%, the accuracy is 96.09%, and the specificity of 95.16% is achieved in the MIT-BIH normal sinus rhythm database. The experimental results show that the proposed method is an effective classification method for atrial fibrillation.
10.Research on the influence of flight attitude display on the operation of unusual attitude recovery
Hongyu CHEN ; Yuntao GAO ; Hong DAI ; Litong ZHENG ; Yan WU
Chinese Journal of Aerospace Medicine 2018;29(3):188-194
Objective To reduce flight accidents and ensure aviation safety by comparing the combination effects of three attitude directional indicator (ADI ) designs and two reference frames [moving horizon (MH) and moving aircraft (MA)] on the operation of aircraft unusual attitude recovery. Methods The simulated recovery experiments were carried out by E-prime programming the interactively matched pictures that were presented by the regular perspective-view aircraft symbol (PAS) under unusual flight altitude and two reference frames that referenced MH and MA.The subjects were 34 male college students in the full-time military academy ,with average age of (22.43 ± 1.32) years old.The experiment was done based on 2×3×4 intra-test design.The combination of 2 reference frames and 3 ADI styles produced six displays and each of them corresponded to 8 rotation altitudes.Totally 48 pictures were displayed.During learning phase , the usual or unusual flight altitude pictures were presented to the subjects and the recovery operation was instructed to press the"F"key for the recovery to the left and the "J" key to the right.During training phase ,4 unusual flight altitude pictures were presented to the subjects.When the subjects were able to correctly judge these 4 pictures they were thought to be ready for the formal experiment.In formal experiment ,48 pictures were randomly presented to the subjects and the reaction time and the number of correct recovery were recorded. Results The intra-group variance analysis with reaction time as the dependent variable indicated that the effect of the interaction between ADI style and reference frame on subjects′reaction time was statistically significant ,[F(2 ,66)=6.267 , P=0.003 ,η2 =0.160].The combination of conventional ADI format and PAS format with MA reference frame showed better matched effect.The intra-group analysis of the variance with correct rate as the dependent variable indicated that the effect of interaction between the ADI style and the reference frame on subjects′correct rate was statistically significant [F(2 ,66)= 12.018 , P < 0.001 ,η2 = 0.267].The MH reference frame matched with 3 ADI formats showed better results than the CMD-MA display and the CON-MA display.PAS-MA design also showed good performance. Conclusions ① Two new ADI formats (CMD ,PAS) show certain advantages that traditional and conventional ADI format (CON) does not have.②The M H reference frame has the advantage on overall correct recovery rate.③The study theoretically recommends the PAS-MA display design.


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