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.Enzymatic depolymerization of polyester-cotton textiles for the recovery of terephthalic acid.
Hongzhao WANG ; Yuntao CUN ; Minxuan WANG ; Zhenwu YANG ; Hao HE ; Yushan ZHU
Chinese Journal of Biotechnology 2025;41(9):3553-3566
Polyethylene terephthalate (PET) fibers are characterized by exceptional mechanical strength, and textiles blended with cotton fibers combine both comfort and durability, showcasing widespread use in daily applications. However, improper disposal of discarded polyester-cotton textiles has resulted in severe environmental pollution, necessitating urgent and effective mitigation strategies. Enzymatic recycling of textiles offers superior environmental benefits and holds greater potential for industrial applications than alternative recycling methods. This study aims to explore a large-scale solution for the treatment of waste textiles, particularly addressing the challenge of resource recovery from polyester-cotton blended fabrics. An innovative enzymatic depolymerization process has been developed to achieve the recovery of high-purity terephthalic acid monomers. Experiments were conducted on three different textile blends with polyester-to-cotton ratios of 65/35, 70/30, and 80/20, and the influences of different colors on the process were investigated. Initially, the textiles were pretreated through mechanical grinding, which was followed by depolymerization of cotton fibers with commercial cellulase. The crystallinity of PET in the textiles was reduced through a rapid heating and cooling process. Subsequently, the PET was depolymerized by the engineered PET hydrolase. The results demonstrated that after decolorization and separation of terephthalic acid (TPA) from the reaction system, the monomer recovery rates for the three textile blends (65/35, 70/30, and 80/20) reached 90%, 91%, and 92%, respectively. Characterization analysis by nuclear magnetic resonance (NMR) confirmed that the purity of the recovered TPA was greater than 99%. In conclusion, the fully enzymatic recycling process developed in this study shows considerable promise for large-scale industrial applications and is anticipated to significantly advance the adoption and development of enzymatic recycling technologies for PET in industrial processes.
Phthalic Acids/chemistry*
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Polyesters/chemistry*
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Textiles
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Cotton Fiber
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Polyethylene Terephthalates/chemistry*
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Cellulase/chemistry*
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Recycling/methods*
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Polymerization
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.Chemical Consistency of Lycii Cortex from Different Origins Based on Component Contents and Fingerprint
Baoxin LI ; Lixia HAO ; Yuntao DAI ; Xiwen LI ; Lan WU
Chinese Journal of Experimental Traditional Medical Formulae 2022;28(24):179-185
ObjectiveIn this study, the two different origins of Lycii Cortex in the 2020 edition of Chinese Pharmacopoeia were determined to analyze their chemical consistency by comparing their main chemical composition. MethodThirty representative batches of Lycii Cortex were collected, content determination and fingerprint analysis methods were established by ultra performance liquid chromatography-photodiode array detector (UPLC-PDA) combining with multivariate statistical analysis to evaluate the similarities and differences between two origins of Lycii Cortex. Respectively by the mobile phase of acetonitrile (A)-0.15% trifluoroacetic acid aqueous solution (B) and the mobile phase of acetonitrile (A)-0.1% formic acid aqueous solution (B) for gradient elution (0-4 min, 5%-12%A; 4-8 min, 12%A; 8-12 min, 12%-14%A; 12-15 min, 14%-30%A; 15-17 min, 30%-40%A; 17-18 min, 40%-90%A), and the detection wavelength was set at 280 nm. ResultThis established content determination and fingerprint methods had good precision, stability and repeatability. The similarities of 30 batches of Lycii Cortex were above 0.90 by comparing with the control fingerprint, and the eight common peaks in fingerprints of Lycii Cortex from Lycium barbarum and L. chinense were all phenolic amides, which were kukoamine B, N-(4,9,13-triazatridecan-1-yl)-3,4-dihydroxybenzenepropanamide, feruloylputrescine, N1,N5-bis (dihydrocaffeoyl) spermidine or N5,N10-bis (dihydrocaffeoyl) spermidine, N5-caffeoyl-N10-dihydrocaffeoylspermidine, N5-dihydrocaffeoyl-N10-caffeoylspermidine, N1,N5-bis (caffeoyl) spermidine and lyciumin A. Among them, the content ranges of kukoamine B in Lycii Cortex from L. chinense and L. barbarum were 1.22%-8.18%, 2.52%-12.24%, respectively. ConclusionThe established UPLC analysis method can be used for the content determination and fingerprint analysis of Lycii Cortex. This study indicates that chemical contour of Lycii Cortex from L. barbarum and L. chinense are similar, there are no significant differences in kukoamine B content, and they have consistency in the chemical composition.
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.Clinical efficacy of conformal sphincter preservation operation versus intersphincteric resection in the treatment of low rectal cancer
Ge SUN ; Yiwen ZANG ; Haibo DING ; Yuntao CHEN ; Haifeng GONG ; Zheng LOU ; Liqiang HAO ; Ronggui MENG ; Zongyou CHEN ; Jianbin XIANG ; Wei ZHANG
Chinese Journal of Digestive Surgery 2021;20(3):292-300
Objective:To investigate clinical efficacy of conformal sphincter preservation operation (CSPO) versus intersphincteric resection (ISR) in the treatment of low rectal cancer.Methods:The retrospective cohort study was conducted. The clinicopathological data of 183 patients with low rectal cancer who were admitted to two medical centers (117 in the Changhai Hospital of Naval Medical University and 66 in the Huashan Hospital of Fudan University) from August 2011 to April 2020 were collected. There were 110 males and 73 females, aged (57±11)years. Of 183 patients, 117 cases undergoing CSPO were allocated into CSPO group, and 66 cases undergoing ISR were allocated into ISR group, respectively. Observation indicators: (1) surgical situations of patients with low rectal cancer in the two groups; (2) postoperative complications of patients with low rectal cancer in the two groups; (3) follow-up; (4) influencing factors for prognosis of patients with low rectal cancer; (5) influencing factors for satisfaction with the anal function of patients with low rectal cancer. Follow-up was conducted using outpatient examination, questionnaire and telephone interview to determine local recurrence, distal metastasis, survival, stomal closure, satisfaction with the anal function of patients. Measurement data with normal distribution were represented as Mean±SD, and comparison between groups was analyzed using the t test. Measurement data with skewed distribution were represented as M (range). Count data were described as absolute numbers or percentages, and comparison between groups was analyzed using the chi-square test. Comparison of ordinal data was analyzed using the rank sum test.The Kaplan-Meier method was used to draw survival curves, and life table method was used to calculate survival rates. Log-rank test was used for survival analysis. Univariate analysis was performed using the linear regression. Variables with P<0.10 in the univariate linear regression analysis were included for multivariate analysis. Multivariate analysis was performed using the COX stepwise regression model and linear regression analysis. Results:(1) Surgical situations of patients with low rectal cancer in the two groups: cases with laparoscopic surgery, operation time, volume of intraoperative blood loss, distance from tumor to distal margin, cases with postoperative chemotherapy, duration of postoperative hospital stay were 44, (165±54)minutes, (142±101)mL, (0.6±0.4)cm, 76, (6.6±2.5)days for the CSPO group, respectively, versus 55, (268±101)minutes, (91±85)mL, (1.9±0.6)cm, 9, (7.9±4.7)days for the ISR group, showing significant differences between the two groups ( χ2=35.531, t=8.995, -3.437, -3.088, χ2=44.681, t=2.267, P<0.05). (2) Postoperative complications of patients with low rectal cancer in the two groups: 19 patients in the CSPO group had complications. There were 6 cases with grade Ⅰ complications, 12 cases with grade Ⅱ complications, 1 case with grade Ⅲb complication. Fourteen patients in the ISR group had complications. There were 4 cases with grade Ⅰ complications, 7 cases with grade Ⅱ complications, 1 case with grade Ⅲa complication, 2 cases with grade Ⅲb complications. There was no significant difference in the postoperative complications between the two groups ( χ2=0.706, P>0.05). Patients with complications in the two groups were improved after symptomatic and supportive treatment. There was no perioperative death in the postoperative 30 days of the two groups. (3) Follow-up: 183 patients received follow-up. Patients of the CSPO group and ISR group were followed up for (41±27)months and (37±19)months, respectively, showing no significant difference between the two groups ( t=-1.104, P>0.05). There were 2 cases with local recurrence and 9 cases with distal metastasis of the CSPO group, respectively, versus 3 cases and 4 cases of the ISR group, showing no significant difference between the two groups ( χ2=1.277, 0.170, P>0.05). The 3-year disease-free survival rate and 3-year total survival rate were 84.0% and 99.0% for the CSPO group, versus 88.6% and 92.8% for the ISR group, showing no significant difference between the two groups ( χ2=0.218, 0.002, P>0.05). The stomal closure rate was 92.16%(94/102) and 96.97%(64/66) for 102 patients of CSPO group and 66 patients of ISR group up to postoperative 12 months,respectively, showing no significant difference between the two groups ( χ2=1.658, P>0.05). Of the 8 cases without stomal closure in the CSPO group, 2 cases refused due to advanced age, 4 cases subjectively refused, and 2 cases were irreducible due to scar caused by radiotherapy. Two cases in the ISR group had no stomal closure including 1 case of postoperative liver metastasis and 1 case of subjective refusal. There were 92 and 61 patients followed up to 12 months after stomal closure, of which 75 cases and 38 cases completed questionnaires of satisfaction with the anal function. The satisfaction score with the anal function was 6.8±2.8 and 5.4±3.0 for CSPO group and ISR group, respectively, showing a significant difference between the two groups ( t=-2.542, P<0.05). Fifty-four cases in the CSPO group and 21 cases in the ISR group had satisfaction score with the anal function >5, showing no significant difference between the two groups ( χ2=3.165, P>0.05). (4) Influencing factors for prognosis of patients with low rectal cancer: results of COX stepwise regression analysis showed that gender and pT staging were independent influencing factors for disease-free survival rate of patients with low rectal cancer ( hazard ratio=2.883, 1.963, 95% confidence interval as 1.090 to 7.622, 1.129 to 3.413, P<0.05). Gender and pT staging were independent influencing factors for total survival rate of patients with low rectal cancer ( hazard ratio=10.963,3.187, 95% confidence interval as 1.292 to 93.063, 1.240 to 8.188, P<0.05). (5) Influencing factors for satisfaction with the anal function of patients with low rectal cancer: results of univariate analysis showed that surgical method and tumor differentiation degree were related factors for satisfaction with the anal function of patients with low rectal cancer (partial regression coefficient=1.464, -1.580, 95% confidence interval as 0.323 to 2.605, -2.950 to -0.209, P<0.05). Results of multivariate analysis showed that surgical method, tumor differentiation degree and preoperative radiotherapy were independent influencing factors for satisfaction with the anal function of patients with low rectal cancer (partial regression coefficient=1.637, -1.456, -1.668, 95% confidence interval as 0.485 to 2.788, -2.796 to -0.116, -2.888 to -0.447, P<0.05). Conclusion:Compared with ISR, CSPO can safely preserve the anus in the treatment of low rectal cancer, without increasing the incidence of postoperative complications, which can also guarantee the oncological safety and improve the postoperative anal function.
7. The value of multi-gene testing in benign or malign diagnosis of thyroid nodules with indeterminate cytology
Yuntao SONG ; Guohui XU ; Yanli ZHU ; Tonghui MA ; Hao YU ; Tianxiao WANG ; Wenbin YU ; Wei WEI ; Bin ZHANG
Chinese Journal of Otorhinolaryngology Head and Neck Surgery 2019;54(10):764-768
Objective:
To study the diagnostic value of a multi-gene molecular testing in cytologically indeterminate thyroid nodules.
Methods:
From February 2018 to September 2018, patients with thyroid nodules who underwent fine needle aspiration(FNA) at Peking University Cancer Hospital were enrolled. Three hundred and sixty patients were included, consisting of 86 men and 274 women, with a mean age of 45.8 years (between 13 and 89 years old). Among 391 nodules, 141 were cytologically inderminate and 75 were resected. FNA samples underwent prospective testing using a next-generation sequencing (NGS) assay, which included 16 genes for point mutations and 26 types of gene fusions. The testing results of indeterminate nodules were compared with surgical outcomes, to determine the diagnostic performance. The results were compared with the
8.Overexpression of MST1 inhibits the proliferation , migration and invasion of cervical cancer cell line SiHa
Xiaoying ZHENG ; Yuntao HAO ; Weijun MA ; Li HAN ; Shumin ZHAO ; Xiangyao LIAN ; Yujuan ZHANG
Basic & Clinical Medicine 2017;37(3):351-354
Objective To discuss the effect of MST1 (mammalian sterile 20-like kinase 1,MST1) on the prolifera-tion,migration and invasion of SiHa cervical cancer .Methods Western blot was used to detect the expression of MST1 in cervical epithelial cells H8 and cervical cancer cells SiHa;PJ3H-HA-MST1 was constructed and transfect-ed it to SiHa cells by Lipofectamine TM3000;MST1, Ki-67 and MMP9 protein expression were evaluated by Western blot;While the proliferation ,migration and invasion of SiHa cell were assessed by MTS ,scratch adhesion test and Transwell assay respectively .Results Compared SiHa cells with H 8 cells,MST1 expression in SiHa cells was sig-nificantly lower than that in H8 cells.The plasmid was successfully transfected into SiHa cells , MST1 expression was significantly higher , while the expression of Ki-67 and MMP9 was lower .The proliferation , migration and inva-sion ability were all significantly suppressed .Conclusions Overexpression of MST1 can inhibit the proliferation , migration and invasion of cervical cancer cell line SiHa .
9.Expression and clinical significance of MST1 in cervical cancer
Xiaoying ZHENG ; Yuntao HAO ; Shumin ZHAO ; Meina LIU ; Xiujun LIANG
Tianjin Medical Journal 2017;45(4):402-405
Objective To investigate the expression and clinical significance of mammalian sterile 20-like kinase 1 (MST1) in cervical cancer. Methods Immunohistochemical method was applied to detect the expression level of MST1 protein in specimens of cervical cancer tissues (n=139) and pericarcinomatous tissues (n=20, with≥4 cm distance from the primary tumor's edge). Western blot assay and qPCR were used to detect the protein and mRNA transcription expression levels of MST1 in 20 pairs of cervical cancer tissues and pericarcinomatous tissues, respectively. The correlation between MST1 expression, clinic pathological features and the prognosis were analyzed. Results MST1 was mainly expressed in cytoplasm. The positive expression rate of MST1 was significantly lower in cervical cancer tissues (27%, 38/139) than that in pericarcinomatous tissues (80%, 16/20,χ2=21.62, P<0.01). The expressions levels of MST1 protein and mRNA were both lower in the cervical cancer tissues (P<0.01). In cervical cancer, the positive expression rate of MST1 inⅠb+Ⅱa stage was higher than that ofⅡb+Ⅳstage (P<0.05), the positive expression rate of MST1 in lymph node metastasis was lower than that of without lymph node metastasis (P < 0.05). Values of age, tumor size, histological type and differentiation degree showed no significant difference to positive expression rate of MST1. Moreover, the negative expression of MST1 displayed a significantly poorer overall survival time than that of positive expression of MST1 (Log-rank χ2=28.35, P < 0.01). Conclusion MST1 shows a lower expression in cervical cancer, which may be a new target for clinical treatment and prognosis of cervical cancer.
10.Clinical prediction value of chemokine CCL21 level for acute coronary syndrome
Zhengwei ZHANG ; Ming LIU ; Lufei LI ; Yuntao HAO ; Hongwei ZHANG
Chinese Journal of Geriatrics 2017;36(4):403-407
Objective To investigate the clinical prediction value of chemokine CCL21 level for acute coronary syndrome.Methods Totally 212 patients receiving coronary arteriography were divided into acute myocardial infarction group(AMI,n=72),unstable angina pectoris group(UAP,n=76),and stable angina pectoris group(SAP,n=64).The serum level of chemokine CCL21 was detected by double-antibody sandwich enzyme-linked immunosorbent assay (ELISA)and the pathological changes of coronary artery were measured by Gensini scoring system.All patients were followed up for six months and the cardiovascular adverse events were recorded.Results The serum level of CCL21 was(169.72±14.64)ng/L in AMI group,(154.42±16.50)ng/L in UAP group,and(143.87±9.80) ng/L in SAP group,with statistically significant differences (F =99.818,P =0.000).Serum levels of CCL21 in ACS group and SAP group were positively correlated with Gensini score(r=0.474,P =0.000;r=0.350,P=0.049).Binary Logistic regression analysis revealed that chemokine CCL21 was an independent risk factor for predicting acute coronary syndrome (OR =1.049,P =0.022).The CCL21-judged area under the ROC curve in acute coronary syndrome group was 0.887 ± 0.028 (P =0.000),with diagnostic point of serum level of chemokine CCL21 at 159.15 ng/L,sensitivity of 0.635,specificity of 0.981.Serum level of CCL21 was higher in the patients with cardiovascular adverse events than in the patients without cardiovascular adverse events[(168.57±7.24)ng/L vs.(156.92± 6.53) ng/L],with statistically significant difference (t =16.100,P =0.000).Conclusions Serum level of chemokine CCL21 reflects the severity degree of coronary artery disease.The chemokine CCL21,as an independent and effective marker,can predict acute coronary syndrome.

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