1.A novel loop-structure-based bispecific CAR that targets CD19 and CD22 with enhanced therapeutic efficacy against B-cell malignancies.
Lijun ZHAO ; Shuhong LI ; Xiaoyi WEI ; Xuexiu QI ; Qiaoru GUO ; Licai SHI ; Ji-Shuai ZHANG ; Jun LI ; Ze-Lin LIU ; Zhi GUO ; Hongyu ZHANG ; Jia FENG ; Yuanyuan SHI ; Suping ZHANG ; Yu J CAO
Protein & Cell 2025;16(3):227-231
2.Prenatal diagnosis and perinatal outcomes of non-anterior placenta accreta:A comparative study with anterior placenta accreta
Fan HONG ; Xiaoyi WANG ; Xinyue LIANG ; Jingjin GONG ; Yuqin LEI ; Zhi-Jian WANG
The Journal of Practical Medicine 2024;40(21):2989-2995
Objective To investigate the prenatal diagnosis and perinatal outcomes between anterior pla-centa accreta and non-anterior placenta.Methods A retrospective analysis was done for 560 pregnant women who were diagnosed with placenta accreta and delivered in the Third Affiliated Hospital of Guangzhou Medical Uni-versity.According to the location of the placenta,the group was dividing into anterior placenta accreta group(319 cases)and non-anterior placenta accreta group(241 cases).The general characteristics,maternal and infant out-comes of the two groups were analyzed.The non-anterior placenta accrete group(241 cases)then were dividing into two groups according to the time of clear diagnosis.Those who were firstly diagnosed with placenta accrete dur-ing or after the operation was the intrapartum diagnosis group(missed diagnosis)(70 cases),and those who were diagnosed with clear placenta accreta before the delivery was prenatal diagnosis group(171 cases).The general characteristics,maternal and infant outcomes of the two groups were also analyzed.Results There were statisti-cally significant differences in the parity,history of cesarean section,delivery mode,degree of placenta accreta,missed diagnosis rate,neonatal birth weight,and hysterectomy rate between the non-anterior placenta accrete group and the anterior placenta accreta group.In the case of prenatal diagnosis of different degrees of placenta accreta,the prenatal diagnosis rate of placental adhesion in the non-anterior placenta accreta group was lower than that of the anterior placenta accreta group,which was statistically significant.In the non-anterior placenta accrete group,there were statistically significant differences in the age,cesarean section history,placenta previa status,mode of delivery,degree of implantation,24-hour bleeding volume,blood transfusions,NICU transfer rate,uterine loss rate between the intrapartum diagnosis group(missed diagnosis)and the prenatal diagnosis group.Conclusions The high-risk factors of patients with non-anterior placenta accreta are different from those of patients with anterior placenta accreta.Multiple births and a history of cesarean section are high-risk factors for anterior placenta accreta patients.Non-anterior placenta accreta are more likely to be missed diagnosed,especially the placental adhesion.For pregnant women with non-anterior placenta accreta missed diagnosis,there is a high rate of adverse birth out-comes,especially in the rate of neonatal transfer to the NICU.
3.Advancements in Latest Fusion Gene Detection Methods
Zhiyuan ZHANG ; Zhi ZHENG ; Xiaoyi TIAN
Journal of Modern Laboratory Medicine 2024;39(5):205-212
Fusion genes are new sequences formed by the recombination of two or more gene fragments in the genome that play an important biological role and have clinical significance in the proces of tumorigenesis and development.The detection of fusion genes can provide important guidance for early diagnosis,risk stratification and targeted therapy of tumors.Traditional fusion gene detection methods dominate clinical applications,but have limitations such as low sensitivity,high cost or technical complexity,making them difficult to apply on a large scale.Fortunately the rapid advancements of new biotechnology,a series of new fusion gene detection methods are gradually emerging,providing new alternatives for fusion gene detection.This article reviews traditional fusion gene detection methods and the sequencing technologies developed in recent years,aiming to provide ideas for the detection of fusion genes and guidance for the diagnosis and precise treatment of related diseases.
4.Construction of 177Lu-labeled affibody radiopharmaceutical targeting HER2 and its evaluation in tumor xenografts
Jiayue LIU ; Xiaoyi GUO ; Hua ZHU ; Zhi YANG
Chinese Journal of Nuclear Medicine and Molecular Imaging 2024;44(6):324-329
Objective:To prepare an affinity-based radionuclide therapeutic drug targeting human epidermal growth factor receptor 2 (HER2), named 177Lu-1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid (DOTA)-HER2-BCH, and preliminarily evaluate its biodistribution, therapeutic efficacy, and safety in HER2-positive tumor models, in order to explore its feasibility as a radiopharmaceutical for treatment of HER2-positive tumor. Methods:177Lu labeling was accomplished by using a hydrochloric acid-sodium acetate buffer system. The radiochemical purity and in vitro stability of the labeled products were analyzed by radio high performance liquid chromatography. Biodistribution, 177Lu-DOTA-HER2-BCH radionuclide targeting therapy, and trastuzumab therapy were performed in the HER2-positive NCI-N87 tumor-bearing mice. Repeated measures analysis of variance and Bonferroni method were utilized to analyze data. Results:177Lu-DOTA-HER2-BCH was obtained, with the radiolabeling yield >80%, radiochemical purity >98%, and good in vitro stability. Biodistribution data showed that 177Lu-DOTA-HER2-BCH was well targeted, with high tumor uptake and high retention. The tumor uptake values at 4, 24, 72 and 96 h post-injection were (11.93±0.46), (8.65±0.40), (5.89±0.69) and (3.26±0.36) percentage activity of injection dose per gram of tissue (%ID/g), respectively. In the treatment experiment, 177Lu-DOTA-HER2-BCH significantly inhibited tumor growth. On the 3rd day, the tumor volume of mice treated with 177Lu-DOTA-HER2-BCH was significantly smaller than that of the control group (mean difference 146.97 mm 3;F=4.02, P=0.016 (Bonferroni correction method), and then differences of tumor volume between the 2 groups increased with time. The differences of tumor volume between 177Lu-DOTA-HER2-BCH and trastuzumab treatment groups were not statistically significant throughout the treatment process ( F values: 0.05-61.21, all P>0.017(Bonferroni correction method)). At the end of treatment, no histological abnormality was seen in all organs of the mice. Conclusion:177Lu-DOTA-HER2-BCH radionuclide therapy demonstrates good tumor growth inhibition in HER2-positive tumor-bearing mice, which is expected to be an alternative treatment for HER2-positive tumors.
5.Efficacy of thoracoscopic segmentectomy of the dominant lung segment versus thoracoscopic segmentectomy of the complex lung segment for the treatment of stage I non-small cell lung cancer
Yiping ZHENG ; Xianguo CHEN ; Xiaoyi XU ; Xianshuai LI ; Qianwen ZHI
Chinese Journal of Primary Medicine and Pharmacy 2023;30(11):1640-1645
Objective:To investigate the efficacy of thoracoscopic segmentectomy of the dominant lung segment versus thoracoscopic segmentectomy of the complex lung segment for the treatment of stage I non-small cell lung cancer (NSCLC). Methods:This is a case-control study. The clinical data of 110 patients with stage I NSCLC who received treatment in Jinhua Municipal Central Hospital from August 2019 to August 2021 were retrospectively analyzed. These patients were assigned to a control group (thoracoscopic segmentectomy of dominant lung segment, n = 58) and an observation group (thoracoscopic segmentectomy of complex lung segment n = 52) according to the surgical method. Tumor location and resection scope in each group were recorded. Perioperative indexes, lung function indexes, complications, and short-term recurrence rates were compared between the two groups. Results:The operative time in the observation group was (175.45 ± 30.72) minutes, which was significantly longer than (152.41 ± 29.83) minutes in the control group ( t = 3.99, P < 0.05). The number of nail bins in the observation group was (4.55 ± 1.23), which was significantly greater than (3.77 ± 1.16) in the control group ( t = 3.42, P < 0.05). There were no significant differences in intraoperative bleeding volume, the number of dissected lymph nodes, postoperative drainage volume, postoperative extubation time, and postoperative hospital stay between the two groups (all P > 0.05). Forced vital capacity, forced expiratory volume in the first second (FEV 1), and FEV l/FVC ratio in the observation group were (3.89 ± 0.47) L, (2.92 ± 0.36) L, and (75.06 ± 2.47)%, which were significantly higher than (3.64 ± 0.49) L, (2.68 ± 0.35) L, and (73.63 ± 2.38)% in the control group (all P < 0.05). There was a significant difference in the incidence of complications between the observation and control groups [32.69% (17/52) vs. 20.69% (12/58), P > 0.05]. There was no significant difference in recurrence of stage I NSCLC between the observation and control groups [3.85% (2/52) vs. 1.72% (1/58), P = 0.495]. Conclusion:The overall effect and safety of thoracoscopic segmentectomy of complex lung segment in the treatment of stage I NSCLC are comparable to those of thoracoscopic segmentectomy of the dominant lung segment. However, thoracoscopic segmentectomy of complex lung segments can reduce the impact on lung function and protect lung function to the maximum extent.
6.Construction of tissue engineered cell sheet.
Fuan XIAO ; Xueting JIAN ; Xiaoyi FENG ; Junyan TAN ; Wanling XIONG ; Ye ZHI ; Yuan XU ; Yang LIU
Chinese Journal of Biotechnology 2021;37(7):2405-2413
Scaffold-free tissue engineered cell sheet is an emerging technology in biomedical field. It can avoid the adverse effects of scaffold materials, and can be further assembled to form more complex three-dimensional functional tissues. The construction of cell sheet is mainly based on the culture substrate composed of sensitive materials. By changing the stimulation factors such as temperature, enzyme, light, ion, redox, pH and sugar, the adhesion behavior of the substrate to the cells could be changed to make the cells detach naturally, thus generating the cell sheet. Recent years have seen the development of various simple and efficient construction technologies of cell sheet due to the development of a variety of novel sensitive culture substrates. The resulted cell sheets with excellent performance have greatly expanded their applications. This review summarized the construction methods of tissue engineered cell sheet and discussed the challenges and future perspectives in this field.
Temperature
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Tissue Engineering
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Tissue Scaffolds
7.Genome-wide 5-Hydroxymethylcytosine Profiling Analysis Identifies MAP7D1 as A Novel Regulator of Lymph Node Metastasis in Breast Cancer
Wu SHUANG-LING ; Zhang XIAOYI ; Chang MENGQI ; Huang CHANGCAI ; Qian JUN ; Li QING ; Yuan FANG ; Sun LIHONG ; Yu XINMIAO ; Cui XINMIAO ; Jiang JIAYI ; Cui MENGYAO ; Liu YE ; Wu HUAN-WEN ; Liang ZHI-YONG ; Wang XIAOYUE ; Niu YAMEI ; Tong WEI-MIN ; Jin FENG
Genomics, Proteomics & Bioinformatics 2021;19(1):64-79
Although DNA 5-hydroxymethylcytosine (5hmC) is recognized as an important epige-netic mark in cancer, its precise role in lymph node metastasis remains elusive. In this study, we investigated how 5hmC associates with lymph node metastasis in breast cancer. Accompanying with high expression of TET1 and TET2 proteins, large numbers of genes in the metastasis-positive pri-mary tumors exhibit higher 5hmC levels than those in the metastasis-negative primary tumors. In contrast, the TET protein expression and DNA 5hmC decrease significantly within the metastatic lesions in the lymph nodes compared to those in their matched primary tumors. Through genome-wide analysis of 8 sets of primary tumors, we identified 100 high-confidence metastasis-associated 5hmC signatures, and it is found that increased levels of DNA 5hmC and gene expression of MAP7D1 associate with high risk of lymph node metastasis. Furthermore, we demonstrate that MAP7D1, regulated by TET1, promotes tumor growth and metastasis. In conclusion, the dynamic 5hmC profiles during lymph node metastasis suggest a link between DNA 5hmC and lymph node metastasis. Meanwhile, the role of MAP7D1 in breast cancer progression suggests that the metastasis-associated 5hmC signatures are potential biomarkers to predict the risk for lymph node metastasis, which may serve as diagnostic and therapeutic targets for metastatic breast cancer.
8.Production and purification of solid target PET nuclide 89Zr and its antibody labeling
Feng WANG ; Xiaoyi GUO ; Teli LIU ; Lixin DING ; Lei XIA ; Jin DING ; Xiangxi MENG ; Jinquan JIANG ; Hua ZHU ; Zhi YANG
Chinese Journal of Nuclear Medicine and Molecular Imaging 2020;40(5):294-297
Objective:To produce the solid target nuclide 89Zr , and prepare the probe 89Zr-desferrioxamine (DFO)-Trastuzumab. Methods:The 89Y(p, n) 89Zr nuclear reaction was used for 89Zr production. 89Y target was irradiated by 20 μA proton in a medical cyclotron ( E=12.5 MeV) for about 1-2 h. 89Zr was purified from hydroxamate resin using 1 mol/L oxalic acid solution. The characteristic peak, radionuclide purity and radiochemical purity of 89Zr were determined by γ-ray spectroscopy. 89Zr-DFO-Trastuzumab probe was synthesized by the reaction of 89Zr-oxalate and DFO-Trastuzumab at room temperature, and the radiochemical purity was measured. Results:89Zr was prepared successfully for 11 times, and the production of 89Zr was 555-1 506 MBq, with production rate of (34.8±5.2) MBq·μA -1·h -1. After the purification (purification rate: 42%-87%), 227.2-991.6 MBq 89Zr was obtained, with the concentration of 1.0×10 6 MBq/L. The γ spectrum showed that the characteristic peak of 89Zr were 511 and 909 keV, and no impurities were found. The radionuclide purity and radiochemical purity were both close to 100%. 89Zr-DFO-Trastuzumab was successfully labeled with radiochemical purity more than 95%, and it was above 90% within 72 h in human serum albumin (HSA) solution. Conclusion:Through the self-designed target assembling, the solid target PET nuclide 89Zr with high quality and labeling are successfully achieved, which provides guarantee for the clinical application of the 89Zr drug.
9. Progress in research on tumor immune PD-1/PD-L1 signaling pathway in malignant bone tumors
Haifeng HUANG ; Hua ZHU ; Xianteng YANG ; Xiaoyi GUO ; Shanshan LI ; Quan XIE ; Xiaobin TIAN ; Zhi YANG
Chinese Journal of Oncology 2019;41(6):410-414
Programmed death receptor 1 (PD-1) and its ligand PD-L1 have been shown to play an important role in evading the immune system. In recent years, PD-1/PD-L1 blockade has shown significant clinical effects in many malignancies, including malignant melanoma, renal cell carcinoma, classic Hodgkin lymphoma, non-small cell lung cancer and so on. PD-1/PD-L1 signaling pathway has become a new target of immunotherapy in patients with malignant tumors. However, there are few researches on immunotherapy in malignant bone tumors, and the progress of clinical research on PD-1/PD-L1 remains to be elucidated. This review started from the mechanism of PD-1/PD-L1 signaling in tumor immunity, and analyzed the application prospect of PD-1/PD-L1 antibodies in malignant bone tumors. We hope to provide a theoretical basis for the treatment of malignant bone tumors based on PD-1/PD-L1 signaling pathway in China.
10.Preparation and microPET imaging of somatostatin receptor antagonist 68 Ga-NOTA-JR11
Qing XIE ; Hua ZHU ; Teli LIU ; Xiaoyi GUO ; Jiangyuan YU ; Zhi YANG
Chinese Journal of Nuclear Medicine and Molecular Imaging 2019;39(8):473-477
Objective To prepare a novel somatostatin receptor (SSTR) antagonist 68Ga-1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA)-JR11 (Cpa-c(D-Cys-Aph(Hor)-D-Aph(Cbm)-Lys-Thr-Cys)-D-Tyr-NH2 ) tracer and observe its biodistribution and microPET imaging in mice. Methods One ml HCl (0.05 mol/L) containing 68GaCl3(148 MBq) was added into 65μl NaAc (1 mol/L) and 4μg NOTA-JR11. The mixture reacted at 95 ℃ for 15 min, and then was purified with Sep-Pak? C18 Light column to obtain 68 Ga-NOTA-JR11. 68 Ga-NOTA-JR11 was subjected to quality control analysis including radiochemical purity and in vitro stability by radio-high performance liquid chromatography. Biodistribution of 68Ga-NOTA-JR11 (0.37 MBq) in BALB/c mice (n=9) at 5, 30, 60 min postinjection were observed (n=3 for each time point), and the percentage activity of injection dose per gram of tissue (%ID/g) was calculated. 68Ga-NOTA-JR11 (14.8 MBq) microPET imaging of BALB/c mice (n=1) at 60 min postinjection was observed. Results 68 Ga-NOTA-JR11 was obtained successfully within 15 min, with yielding rate of 90%, radiochemical purity of more than 99%, and specific activity of 6. 10 GBq/μmol. The tracer showed excellent stability ( radio-chemical purity:95%) in different buffers within 150 min. The biodistribution was basically consistent with microPET imaging results. 68 Ga-NOTA-JR11 was metabolized through the kidneys and had low uptake in the liver ((0.75±0.26) %ID/g) at 60 min postinjection. Conclusions 68 Ga-NOTA-JR11 can be prepared rapidly, with high yielding rate and radiochemical purity. Biodistribution and imaging results provide basic information for the further study of somatostatin receptor imaging in neuroendocrine tumors.

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