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.Membrane anatomy-toward a new era of pelvic surgery
Hailong LIU ; Huihong JIANG ; Moubin LIN
Chinese Journal of Gastrointestinal Surgery 2024;27(9):891-897
The concept of membrane anatomy has been widely accepted and applied in clinical practice, but there are still many theoretical and practical conflicts. This article elucidates the fundamental concepts and manifestations of membrane anatomy, delineating its comprehensive integration of anatomical and surgical disciplines. Thereafter, this article specifically discusses its differences from the traditional anatomy and surgery, and then clarifies the important role of membrane anatomy as the third generation of surgical anatomy and the new surgical concept for the development of pelvic surgery.
3.Cronkhite-Canada Syndrome Combined with Asymptomatic Novel Coronavirus Infection: A Case Report
Ning ZHANG ; Chenhao YANG ; Liangrui ZHOU ; Xiaohong SUN ; Xiaohong LIU ; Lin KANG ; Ji LI ; Hailong LI
Medical Journal of Peking Union Medical College Hospital 2024;15(2):406-412
This article presents a case study of a patient who had Cronkhite-Canada syndrome in combination with an asymptomatic novel coronavirus infection. The patient exhibited clinical symptoms of loss of appetite, hair and nail loss, and skin pigmentation. Digestive endoscopy revealed widespread and varying-sized polypoid changes in the mucosa of the stomach, duodenum, and colon. During the course of the illness, the patient tested positive for novel coronavirus nucleic acid. Treatment with moderate doses of prednisone resulted in the patient's hair regrowth and decreased skin hypopigmentation. The article provides a summary of the patient's diagnosis and treatment and a review of relevant literature, with the aim of enhancing clinicians' understanding of the disease.
4.Membrane anatomy-toward a new era of pelvic surgery
Hailong LIU ; Huihong JIANG ; Moubin LIN
Chinese Journal of Gastrointestinal Surgery 2024;27(9):891-897
The concept of membrane anatomy has been widely accepted and applied in clinical practice, but there are still many theoretical and practical conflicts. This article elucidates the fundamental concepts and manifestations of membrane anatomy, delineating its comprehensive integration of anatomical and surgical disciplines. Thereafter, this article specifically discusses its differences from the traditional anatomy and surgery, and then clarifies the important role of membrane anatomy as the third generation of surgical anatomy and the new surgical concept for the development of pelvic surgery.
5.Effect of Electroacupuncture on the Expression GLUT4 of Skeletal Muscle in Type-2 Diabetic Rats
Weimin LOU ; Jian LIN ; Hailong LI
Journal of Zhejiang Chinese Medical University 2024;48(6):649-654
[Objective]To observe the effect of electroacupuncture on the expression of glucose transporter 4(GLUT4)of skeletal muscle in rats with type-2 diabetes mellitus,and to elucidate the mechanism of electroacupuncture on blood glucose regulation.[Methods]Twenty-four rats with type-2 diabetes were randomly divided into blank control group,exercise intervention group and electroacupuncture group,with 8 rats in each group.Rats in blank control group did normal activities.After 1 week of adaptation,rats in exercise intervention group began to run on the treadmill for 2 weeks.The rats in electroacupuncture group were adapted for 1 week,and then the electroacupuncture was placed at the Zhusanli acupoint on both sides with continuous wave stimulation for 2 weeks.Fasting blood glucose and insulin resistance index(IRI)were detected before and after the treatment,and the GLUT4 level of rat muscle cells was detected after the treatment.[Results]Compared with before intervention,the fasting blood glucose level of rats with type-2 diabetes in exercise intervention group and electroacupuncture group reduced significantly after intervention(P<0.001,P=0.028),and the IRI was reduced significantly(P<0.001,P<0.001).The differences of fasting blood glucose level and IRI were significant among the three groups after intervention(P<0.001).The difference of level of GLUT4 was also significant among the three groups after intervention(P<0.001).[Conclusion]Electroacupuncture stimulation can significantly decrease the level of blood glucose and IRI,and regulate the level of GLUT4 in skeletal muscle,which may be an important mechanism of regulation.
6.Hemostatic effects of preperitoneal balloon tamponade with different volumes on hemodynamically unstable pelvic fracture-associated arterial and venous hemorrhage in a swine model
Hailong BING ; Chenxi ZHANG ; Liwei SUN ; Fang LI ; Lin LIN ; Liumei LI ; Qinjun CHU ; Xiaogao JIN ; Hongkai LIAN
Chinese Journal of Orthopaedic Trauma 2023;25(6):537-543
Objective:To determine the effects of preperitoneal balloon (PPB) tamponade with different volumes of fluid on hemodynamically unstable pelvic fracture-associated arterial and venous hemorrhage in a swine model.Methods:A model of open-book pelvic fracture with injuries to external iliac vessels was established in 18 female 12-month old Bama miniature pigs. After the successful establishment of hemodynamically unstable pelvic fracture with vascular injury was confirmed by contrast agent imaging, the animals were randomized into 3 even groups ( n=6): a control group (group C) subjected to PPB tamponade with 0 mL fluid injected, group T1 subjected to PPB tamponade with 500-mL fluid injected, and group T2 subjected to PPB tamponade with 1,000-mL fluid injected. The 3 groups were compared in terms of 60-min survival rate, balloon pressure, peritoneal pressure, bladder pressure, 70-min survival rate, blood loss, and infusion volume. Results:There was no statistically significant difference in the basic hemodynamic or other experimental indicators among the 3 groups before experiment, indicating comparability ( P>0.05). The 60-min survival rate in group T2 was 100.0% (6/6), significantly higher than those in group C and group T1 [0.0% (0/6), 0.0% (0/6)] ( P<0.05). After fluid injection, the balloon pressure and preperitoneal pressure in group T2 were respectively (127.2±4.7) mmHg and (34.5±3.6) mmHg, significantly higher than those in group T1 [(78.7±3.8) mmHg and (13.7±2.8) mmHg] and in group C [0 mmHg and (9.0±1.4) mmHg], and the 2 indicators in group T1 were significantly higher than those in group C (all P<0.05). After fluid injection, there was no statistically significant difference among groups C, T1, and T2 in bladder pressure [(6.7±1.0) mmHg, (5.8±1.9) mmHg, and (6.0±1.1) mmHg] or in bleeding volume [(1,163.0±191.3) mL, (1,212.0±148.4) mL, and (975.0±133.2) mL] (all P≥ 0.05). The infusion volume in group T1 [(1,250.0±225.8) mL] was significantly larger than that in group C [(951.7±177.8) mL] ( P<0.05). No colorectal or bladder injuries were found by the anatomy of the experimental animals in 3 groups. Conclusions:PPB tamponade with 1,000-mL fluid injected in a swine model can efficiently control pelvic fracture-associated arterial and venous hemorrhage, and increase the 60-min survival rate with no colorectal or bladder injuries.
7.A case of BMP2 gene variation-caused short stature, facial dysmorphism and skeletal anomalies with or without cardiac anomaly syndrome
Huili XUE ; Min LIN ; Qun GUO ; Hailong HUANG ; Liangpu XU
Chinese Journal of Perinatal Medicine 2023;26(2):155-158
This article reported the genetic analysis of a case diagnosed with fetal micrognathia and cleft palate by mid-trimester ultrasound in two consecutive pregnancies. In the first pregnancy, the pregnant woman delivered a full-term boy transvaginally, who died two weeks after birth and was diagnosed with Pierre Robin sequence (PRS). Chromosome karyotype and genomic copy number variation. In the second pregnancy, the woman underwent amniocentesis due to suspected PRS presenting by fetal cleft palate, micrognathism, and additional ultrasound anomalies. No abnormalities were detected in fetal karyotype or genomic copy number variation. Whole-exome sequencing, bioinformatics analysis, and Sanger sequencing suggested that both the fetus and the firstborn boy inherited a possible pathogenic variant of c.79delG p.E27Sfs*24 in the BMP2 gene from the mother. The pregnancy was terminated after the genetic consultation. Fetal phenotypes in the two fetuses were similar, indicating that short stature, facial dysmorphism, and skeletal anomalies with or without cardiac anomaly in the pedigree were caused by the heterozygous variant of c.79delG p.E27Sfs*24 in the BMP2 gene.
8.Effectiveness of craniocervical flexion training combined with cervical traction among patients with cervical spondylotic radiculopathy
Yang LIU ; Jian LIN ; Hailong LI ; Yichao JI ; Rongrong HU ; Feifei LI
Journal of Preventive Medicine 2023;35(2):104-107
Objective:
To evaluate the effectiveness of craniocervical flexion training using pressure biofeedback combined with cervical traction among patients with cervical spondylotic radiculopathy (CSR).
Methods:
Sixty patients with CSR receiving treatment in Center of Rehabilitation, Zhejiang Hospital from January 2020 to December 2021 were enrolled and randomly assigned into the control and treatment groups, of 30 patients in each group. All patients were given cervical traction, and patients in the treatment group were given additional craniocervical flexion training using pressure biofeedback for successive four weeks. The effectiveness of craniocervical flexion training combined with cervical traction was evaluated using Visual Analogue Scale (VAS), Neck Disability Index (NDI) and the active range of motion (AROM) of cervical flexion, and the neck pain and cervical functions were compared between the two groups before and after treatments using repeated-measures analysis of variance.
Results:
Fifteen men were included in the treatment group, with a mean age of (49.47±5.33) years, mean disease course of (5.53±2.89) months, and mean VAS score of (4.73±1.39) points, and there were no significant differences between the control and treatment groups in terms of gender, age, course of disease or VAS score (P>0.05). The VAS score and NDI were lower 4 weeks post-treatment than pretreatment in both the treatment [VAS score: (2.13±1.01) vs. (4.73±1.39); NDI: (12.17±2.12) vs. (20.20±3.78)] and control groups [VAS score: (2.93±1.11) vs. (4.90±1.21); NDI: (15.23±2.39) vs. (19.60±3.30)], and the AROM of cervical flexion was significantly higher 4 weeks post-treatment than pretreatment in both the treatment [(42.87°±2.99°) vs. (37.50°±2.80°)] and control groups [(41.80°±3.61°) vs. (38.07°±2.99°)]; there was an interaction between time and group, and a higher improvement for cervical functions was seen in the treatment group than in the control group (FVAS =5.119, P=0.027; FNDI=15.473, P<0.001; FAROM=11.443, P<0.001).
Conclusion
Craniocervical flexion training using pressure biofeedback combined with cervical traction may effectively alleviate the neck pain and increase the AROM among patients with CRS, which is more effective to improve patients' cervical functions than cervical traction alone.
9.A method for sensitivity analysis of deviation factor for geometric correction of cone-beam CT system.
Hailong WANG ; Guoqin LIN ; Xiaoman DUAN ; Mengke QI ; Wangjiang WU ; Janhui MA ; Yuan XU
Journal of Southern Medical University 2023;43(7):1233-1240
OBJECTIVE:
To propose a sensitivity test method for geometric correction position deviation of cone-beam CT systems.
METHODS:
We proposed the definition of center deviation and its derivation. We analyzed the influence of the variation of the three-dimensional spatial center of the steel ball point, the projection center and the size of the steel ball point on the deviation of geometric parameters and the reconstructed image results by calculating the geometric correction parameters based on the Noo analytical method using the FDK reconstruction algorithm for image reconstruction.
RESULTS:
The radius of the steel ball point was within 3 mm. The deviation of the center of the calibration parameter was within the order of magnitude and negligible. A 10% Gaussian perturbation of a single pixel in the 3D spatial coordinates of the steel ball point produced a deviation of about 3 pixel sizes, while the same Gaussian perturbation of the 2D projection coordinates of the steel ball point produced a deviation of about 2 pixel sizes.
CONCLUSION
The geometric correction is more sensitive to the deviation generated by the three-dimensional spatial coordinates of the steel ball point with limited sensitivity to the deviation generated by the two-dimensional projection coordinates of the steel ball point. The deviation sensitivity of a small diameter steel ball point can be ignored.
Algorithms
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Calibration
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Cone-Beam Computed Tomography
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Steel
10.Using healthcare failure mode and effect analysis to reduce the emergency waiting risk
Duwei ZHU ; Meiying JIANG ; Shaohua HU ; Yuni LIU ; Juanting ZHOU ; Yiming LIN ; Hailong WANG
Chinese Journal of Practical Nursing 2023;39(6):412-417
Objective:To explore the application of effect of healthcare failure mode and effect analysis (HFMEA) in emergency waiting risk management.Methods:From May 2020 to April 2021, totally 87 902 emergency waiting patients from the First Affiliated Hospital of Anhui Medical University were assigned to control group by cluster sampling method. From May 2021 to April 2022, 80 594 emergency waiting patients were assigned to observed group. The patients in the control group received routine emergency waiting of itinerant management mode. In contrast, the patients in the observed group received emergency waiting risk management mode based on HFMEA. The process risk priority number (RPN) and waiting risk management index between two groups were compared.Results:The mean RPN of the observed group was (98.48 ± 8.27) points, significantly lower than that of the control group (251.27 ± 16.95) points. The nurses′ pre-identification rates of changes in the condition and adverse reaction in the observed group were 10.77%(8680/80 594) and 13.37%(10 775/80 594), which were higher than those in the control group, 5.77%(5072/87 902) and 8.12%(7134/87 902), the differences were statistically significant ( χ2 values were 1402.32 and 1221.66, all P<0.05). Conclusions:The application of HFMEA to optimize the emergency waiting management process can effectively reduce the risk of emergency waiting and improve the quality of emergency waiting management.


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