1.Analysis of propensity score matching of flexible ureteroscopy combined with flexible negative pressure suction sheath in the treatment of infectious renal calculus lithotomy
Yanqing GU ; Zongbao GUO ; Xinyu TANG ; Hongxin LIU ; Jincheng YIN
China Journal of Endoscopy 2025;31(2):1-8
Objective Based on the propensity score matching(PSM),the effect of flexible ureteroscopy combined with flexible negative pressure suction sheath in the treatment of infectious renal calculus lithotomy was analyzed.Methods From April 2022 to April 2024,87 patients with infectious renal calculus in our hospital were selected retrospectively.All patients were treated with flexible ureteroscopic lithotripsy(FURL).According to the different choice of ureteral access sheath(UAS)during operation,they were divided into negative pressure sheath group(n=43)and conventional sheath group(n=44).In the negative pressure sheath group,the flexible negative pressure suction sheath was used for FURL,and in the conventional sheath group,the conventional sheath was used for FURL.The general data of patients with infectious renal calculus between groups were compared,and the indicators were balanced by PSM.The clinical efficacy,perioperative indicators,levels of procalcitonin(PCT)and white blood cell count(WBC)and postoperative complications of patients with infectious renal calculus were compared between the two groups.Results After 1∶1 ratio matching by PSM,42 pairs of patients with infectious renal calculus were obtained,.The stone clearance rate of negative pressure sheath group[90.48%(38/42)]was significantly higher than that of conventional sheath group[71.43%(30/42)](P<0.05).The minimum intrapelvic pressure,average intrapelvic pressure and maximum intrapelvic pressure in the negative pressure sheath group were lower than those in the conventional sheath group,operation time and hospitalization time in the negative pressure sheath group were shorter than those in the conventional sheath group(P<0.05).The levels of PCT and WBC in the negative pressure sheath group were lower than those in the conventional sheath group at 2 h after operation,and the time for PCT and WBC to recover to the normal level were shorter than those in the conventional sheath group(P<0.05).The total incidence of postoperative complications in negative pressure sheath group[9.52%(4/42)]was significantly lower than that in conventional sheath group[28.57%(12/42)](P<0.05).Conclusion Flexible ureteroscopy combined with flexible negative pressure suction sheath is effective in the treatment of renal calculus,which is helpful to reduce intra-operative renal pelvis pressure,shorten operation time,reduce PCT and WBC levels after operation,and promote patients'early recovery with good safety.
2.Changing resistance profiles of Haemophilus influenzae and Moraxella catarrhalis isolates in hospitals across China:results from the CHINET Antimicrobial Resistance Surveillance Program,2015-2021
Hui FAN ; Chunhong SHAO ; Jia WANG ; Yang YANG ; Fupin HU ; Demei ZHU ; Yunsheng CHEN ; Qing MENG ; Hong ZHANG ; Chun WANG ; Fang DONG ; Wenqi SONG ; Kaizhen WEN ; Yirong ZHANG ; Chuanqing WANG ; Pan FU ; Chao ZHUO ; Danhong SU ; Jiangwei KE ; Shuping ZHOU ; Hua ZHANG ; Fangfang HU ; Mei KANG ; Chao HE ; Hua YU ; Xiangning HUANG ; Yingchun XU ; Xiaojiang ZHANG ; Wenen LIU ; Yanming LI ; Lei ZHU ; Jinhua MENG ; Shifu WANG ; Bin SHAN ; Yan DU ; Wei JIA ; Gang LI ; Jiao FENG ; Ping GONG ; Miao SONG ; Lianhua WEI ; Xin WANG ; Ruizhong WANG ; Hua FANG ; Sufang GUO ; Yanyan WANG ; Dawen GUO ; Jinying ZHAO ; Lixia ZHANG ; Juan MA ; Han SHEN ; Wanqing ZHOU ; Ruyi GUO ; Yan ZHU ; Jinsong WU ; Yuemei LU ; Yuxing NI ; Jingrong SUN ; Xiaobo MA ; Yanqing ZHENG ; Yunsong YU ; Jie LIN ; Ziyong SUN ; Zhongju CHEN ; Zhidong HU ; Jin LI ; Fengbo ZHANG ; Ping JI ; Yunjian HU ; Xiaoman AI ; Jinju DUAN ; Jianbang KANG ; Xuefei HU ; Xuesong XU ; Chao YAN ; Yi LI ; Shanmei WANG ; Hongqin GU ; Yuanhong XU ; Ying HUANG ; Yunzhuo CHU ; Sufei TIAN ; Jihong LI ; Bixia YU ; Cunshan KOU ; Jilu SHEN ; Wenhui HUANG ; Xiuli YANG ; Likang ZHU ; Lin JIANG ; Wen HE ; Chunlei YUE
Chinese Journal of Infection and Chemotherapy 2025;25(1):30-38
Objective To investigate the distribution and antimicrobial resistance profiles of clinically isolated Haemophilus influenzae and Moraxella catarrhalis in hospitals across China from 2015 to 2021,and provide evidence for rational use of antimicrobial agents.Methods Data of H.influenzae and M.catarrhalis strains isolated from 2015 to 2021 in CHINET program were collected for analysis,and antimicrobial susceptibility testing was performed by disc diffusion method or automated systems according to the uniform protocol of CHINET.The results were interpreted according to the CLSI breakpoints in 2022.Beta-lactamases was detected by using nitrocefin disk.Results From 2015 to 2021,a total of 43 642 strains of Haemophilus species were isolated,accounting for 2.91%of the total clinical isolates and 4.07%of Gram-negative bacteria in CHINET program.Among the 40 437 strains of H.influenzae,66.89%were isolated from children and 33.11%were isolated from adults.More than 90%of the H.influenzae strains were isolated from respiratory tract specimens.The prevalence of β-lactamase was 53.79%in H.influenzae strains.The H.influenzae strains isolated from children showed higher resistance rate than the strains isolated from adults.Overall,779 strains of H.influenzae did not produce β-lactamase but were resistant to ampicillin(BLNAR).Beta-lactamase-producing strains showed significantly higher resistance rates to these antimicrobial agents than the β-lactamase-nonproducing strains.Of the 16 191 M.catarrhalis strains,80.06%were isolated from children and 19.94%isolated from adults.M.catarrhalis strains were mostly susceptible to both amoxicillin-clavulanic acid and cefuroxime,evidenced by resistance rate lower than 2.0%.Conclusions The emergence of antibiotic-resistant H.influenzae due to β-lactamase production poses a challenge for clinical anti-infective treatment.Therefore,it is very important to implement antibiotic resistance surveillance for H.influenzae and guide rational antibiotic use.All local clinical microbiology laboratories should actively improve antibiotic susceptibility testing and strengthen antibiotic resistance surveillance for H.influenzae.
3.Study on the Improvement Effect of Pinelliae Rhizoma Praeparatum Cum Alumine and Its Active Components on Inflamma-tory Response in Acute Lung Injury
Yanqing XU ; Xinzhi WANG ; Xiaobing CUI ; Yuxin GU ; Qianlin CHEN ; Shengjun CHEN ; Song LI ; Hao WU ; Hongli YU
Journal of Nanjing University of Traditional Chinese Medicine 2025;41(8):1055-1065
OBJECTIVE To investigate the ameliorative effect of Pinelliae Rhizoma Praeparatum Cum Alumine and its effective components on inflammatory response in mice with acute lung injury(ALI).METHODS A mice model of acute lung injury induced by lipopolysaccharide(LPS)was used as the in vivo animal model.The levels of inflammatory factors TNF-α,IL-6,and IL-1β,the total protein concentration,the number of inflammatory cells in bronchoalveolar lavage fluid,the ratio of lung wet weight to dry weight,and the pathological damage of lung tissues were taken as the evaluation indexes.RAW264.7 macrophages induced by LPS were used as the in vitro experimental model,with the mRNA levels of intracellular inflammatory factors TNF-α,IL-1β,and IL-6 as indicators,systematic solvent extraction and silica gel column chromatography were used to separate and screen the effective parts and components of Pinelliae Rhizoma Praeparatum Cum Alumine for treating acute lung injury.The component composition of the effective fractions was analyzed by mass spectrometry,the content of cyclic dipeptide components in the effective fraction was determined,and the anti-in-flammatory activity of cyclic dipeptides was verified in vitro.RESULTS The ethyl acetate extraction fraction obtained by extracting the supernatant of water extraction and ethanol precipitation of Pinelliae Rhizoma Praeparatum Cum Alumine(referred to as the ethyl acetate fraction for short)significantly improved the inflammatory response in mice with acute lung injury and significantly reduced the mRNA levels of TNF-α,IL-1β,and IL-6 in RAW264.7 cells induced by LPS.The Fr.1 fraction isolated from the ethyl acetate frac-tion by silica gel column chromatography had anti-inflammatory effects in vitro.Mass spectrometry determined the content of two main cyclic dipeptide components,cyclo-(Pro-Phe)and cyclo-(Pro-Val),in the Fr.1 fraction.After mixing these two cyclic dipeptide components in the molar ratio in the Fr.1 fraction and administering them in vitro,the results showed that the combination of these two cyclic dipeptide components could significantly inhibit the mRNA expression levels of TNF-α,IL-1β,and IL-6 in RAW264.7 cells induced by LPS.CONCLUSION Cyclic dipeptide component is one of the main material basis categories for the anti-inflammatory effect of Pinelliae Rhizoma Praeparatum Cum Alumine.
4.Study on the Improvement Effect of Pinelliae Rhizoma Praeparatum Cum Alumine and Its Active Components on Inflamma-tory Response in Acute Lung Injury
Yanqing XU ; Xinzhi WANG ; Xiaobing CUI ; Yuxin GU ; Qianlin CHEN ; Shengjun CHEN ; Song LI ; Hao WU ; Hongli YU
Journal of Nanjing University of Traditional Chinese Medicine 2025;41(8):1055-1065
OBJECTIVE To investigate the ameliorative effect of Pinelliae Rhizoma Praeparatum Cum Alumine and its effective components on inflammatory response in mice with acute lung injury(ALI).METHODS A mice model of acute lung injury induced by lipopolysaccharide(LPS)was used as the in vivo animal model.The levels of inflammatory factors TNF-α,IL-6,and IL-1β,the total protein concentration,the number of inflammatory cells in bronchoalveolar lavage fluid,the ratio of lung wet weight to dry weight,and the pathological damage of lung tissues were taken as the evaluation indexes.RAW264.7 macrophages induced by LPS were used as the in vitro experimental model,with the mRNA levels of intracellular inflammatory factors TNF-α,IL-1β,and IL-6 as indicators,systematic solvent extraction and silica gel column chromatography were used to separate and screen the effective parts and components of Pinelliae Rhizoma Praeparatum Cum Alumine for treating acute lung injury.The component composition of the effective fractions was analyzed by mass spectrometry,the content of cyclic dipeptide components in the effective fraction was determined,and the anti-in-flammatory activity of cyclic dipeptides was verified in vitro.RESULTS The ethyl acetate extraction fraction obtained by extracting the supernatant of water extraction and ethanol precipitation of Pinelliae Rhizoma Praeparatum Cum Alumine(referred to as the ethyl acetate fraction for short)significantly improved the inflammatory response in mice with acute lung injury and significantly reduced the mRNA levels of TNF-α,IL-1β,and IL-6 in RAW264.7 cells induced by LPS.The Fr.1 fraction isolated from the ethyl acetate frac-tion by silica gel column chromatography had anti-inflammatory effects in vitro.Mass spectrometry determined the content of two main cyclic dipeptide components,cyclo-(Pro-Phe)and cyclo-(Pro-Val),in the Fr.1 fraction.After mixing these two cyclic dipeptide components in the molar ratio in the Fr.1 fraction and administering them in vitro,the results showed that the combination of these two cyclic dipeptide components could significantly inhibit the mRNA expression levels of TNF-α,IL-1β,and IL-6 in RAW264.7 cells induced by LPS.CONCLUSION Cyclic dipeptide component is one of the main material basis categories for the anti-inflammatory effect of Pinelliae Rhizoma Praeparatum Cum Alumine.
5.Analysis of propensity score matching of flexible ureteroscopy combined with flexible negative pressure suction sheath in the treatment of infectious renal calculus lithotomy
Yanqing GU ; Zongbao GUO ; Xinyu TANG ; Hongxin LIU ; Jincheng YIN
China Journal of Endoscopy 2025;31(2):1-8
Objective Based on the propensity score matching(PSM),the effect of flexible ureteroscopy combined with flexible negative pressure suction sheath in the treatment of infectious renal calculus lithotomy was analyzed.Methods From April 2022 to April 2024,87 patients with infectious renal calculus in our hospital were selected retrospectively.All patients were treated with flexible ureteroscopic lithotripsy(FURL).According to the different choice of ureteral access sheath(UAS)during operation,they were divided into negative pressure sheath group(n=43)and conventional sheath group(n=44).In the negative pressure sheath group,the flexible negative pressure suction sheath was used for FURL,and in the conventional sheath group,the conventional sheath was used for FURL.The general data of patients with infectious renal calculus between groups were compared,and the indicators were balanced by PSM.The clinical efficacy,perioperative indicators,levels of procalcitonin(PCT)and white blood cell count(WBC)and postoperative complications of patients with infectious renal calculus were compared between the two groups.Results After 1∶1 ratio matching by PSM,42 pairs of patients with infectious renal calculus were obtained,.The stone clearance rate of negative pressure sheath group[90.48%(38/42)]was significantly higher than that of conventional sheath group[71.43%(30/42)](P<0.05).The minimum intrapelvic pressure,average intrapelvic pressure and maximum intrapelvic pressure in the negative pressure sheath group were lower than those in the conventional sheath group,operation time and hospitalization time in the negative pressure sheath group were shorter than those in the conventional sheath group(P<0.05).The levels of PCT and WBC in the negative pressure sheath group were lower than those in the conventional sheath group at 2 h after operation,and the time for PCT and WBC to recover to the normal level were shorter than those in the conventional sheath group(P<0.05).The total incidence of postoperative complications in negative pressure sheath group[9.52%(4/42)]was significantly lower than that in conventional sheath group[28.57%(12/42)](P<0.05).Conclusion Flexible ureteroscopy combined with flexible negative pressure suction sheath is effective in the treatment of renal calculus,which is helpful to reduce intra-operative renal pelvis pressure,shorten operation time,reduce PCT and WBC levels after operation,and promote patients'early recovery with good safety.
6.Psychometric validation of the Chinese version of the Vascular Quality of Life Questionnaire-6
Jiali HU ; Yanghui XU ; Xuefang HUANG ; Ya MENG ; Yanqing LI ; Zhifeng GU
Chinese Journal of Modern Nursing 2025;31(21):2815-2821
Objective:To translate the Vascular Quality of Life Questionnaire-6 (VQ6) into a Chinese version and to test its reliability and validity in patients with peripheral arterial disease.Methods:The English version of VQ6 scale was sinicized following the Brislin translation guidelines, and the Delphi consultation was used for cultural debugging to form the Chinese version of the VQ6. Convenience sampling was used to select 146 patients with peripheral arterial disease who attended the Department of Interventional and Vascular Surgery and the Department of Endocrinology of Affiliated Hospital of Nantong University from May to June 2024 for the survey. Data were analyzed using SPSS 26.0 and Amos 26.0. Correlation analysis and critical ratio method were used for item analysis and content validity index was used to evaluate content validity. The Chinese version of the Patient-Reported Outcomes Measurement Information System 29 Profile V2.1 (PROMIS-29 Profile v2.1) was selected as a validity scale to evaluate the criterion-related validity. Exploratory factor analysis and confirmatory factor analysis were used to evaluate the structural validity of the scale, and transgender test was used for measurement equivalence. Reliability of the scale was evaluated with the Cronbach's α coefficient and retest reliability index.Results:The Chinese version of the VQ6 scale had six items. The scale-level content validity index was 0.972, and the item-level content validity index ranged from 0.833 to 1.000. One common factor was extracted with a cumulative variance contribution of 83.526%. Criterion-related validity showed that the correlation coefficient between the Chinese version of the VQ6 and the PROMIS-29 Profile v2.1 was 0.688 ( P<0.01) . The scale essentially satisfied Δ RMSEA < 0.015 and Δ CFI < 0.01 in the transgender equivalence test. The Cronbach's α coefficient for the scale was 0.968 and the retest reliability was 0.978. Conclusions:The Chinese version of the VQ6 has good reliability and validity and is suitable as an assessment tool for quality of life in patients with peripheral arterial disease in our cultural context.
7.Changing resistance profiles of Haemophilus influenzae and Moraxella catarrhalis isolates in hospitals across China:results from the CHINET Antimicrobial Resistance Surveillance Program,2015-2021
Hui FAN ; Chunhong SHAO ; Jia WANG ; Yang YANG ; Fupin HU ; Demei ZHU ; Yunsheng CHEN ; Qing MENG ; Hong ZHANG ; Chun WANG ; Fang DONG ; Wenqi SONG ; Kaizhen WEN ; Yirong ZHANG ; Chuanqing WANG ; Pan FU ; Chao ZHUO ; Danhong SU ; Jiangwei KE ; Shuping ZHOU ; Hua ZHANG ; Fangfang HU ; Mei KANG ; Chao HE ; Hua YU ; Xiangning HUANG ; Yingchun XU ; Xiaojiang ZHANG ; Wenen LIU ; Yanming LI ; Lei ZHU ; Jinhua MENG ; Shifu WANG ; Bin SHAN ; Yan DU ; Wei JIA ; Gang LI ; Jiao FENG ; Ping GONG ; Miao SONG ; Lianhua WEI ; Xin WANG ; Ruizhong WANG ; Hua FANG ; Sufang GUO ; Yanyan WANG ; Dawen GUO ; Jinying ZHAO ; Lixia ZHANG ; Juan MA ; Han SHEN ; Wanqing ZHOU ; Ruyi GUO ; Yan ZHU ; Jinsong WU ; Yuemei LU ; Yuxing NI ; Jingrong SUN ; Xiaobo MA ; Yanqing ZHENG ; Yunsong YU ; Jie LIN ; Ziyong SUN ; Zhongju CHEN ; Zhidong HU ; Jin LI ; Fengbo ZHANG ; Ping JI ; Yunjian HU ; Xiaoman AI ; Jinju DUAN ; Jianbang KANG ; Xuefei HU ; Xuesong XU ; Chao YAN ; Yi LI ; Shanmei WANG ; Hongqin GU ; Yuanhong XU ; Ying HUANG ; Yunzhuo CHU ; Sufei TIAN ; Jihong LI ; Bixia YU ; Cunshan KOU ; Jilu SHEN ; Wenhui HUANG ; Xiuli YANG ; Likang ZHU ; Lin JIANG ; Wen HE ; Chunlei YUE
Chinese Journal of Infection and Chemotherapy 2025;25(1):30-38
Objective To investigate the distribution and antimicrobial resistance profiles of clinically isolated Haemophilus influenzae and Moraxella catarrhalis in hospitals across China from 2015 to 2021,and provide evidence for rational use of antimicrobial agents.Methods Data of H.influenzae and M.catarrhalis strains isolated from 2015 to 2021 in CHINET program were collected for analysis,and antimicrobial susceptibility testing was performed by disc diffusion method or automated systems according to the uniform protocol of CHINET.The results were interpreted according to the CLSI breakpoints in 2022.Beta-lactamases was detected by using nitrocefin disk.Results From 2015 to 2021,a total of 43 642 strains of Haemophilus species were isolated,accounting for 2.91%of the total clinical isolates and 4.07%of Gram-negative bacteria in CHINET program.Among the 40 437 strains of H.influenzae,66.89%were isolated from children and 33.11%were isolated from adults.More than 90%of the H.influenzae strains were isolated from respiratory tract specimens.The prevalence of β-lactamase was 53.79%in H.influenzae strains.The H.influenzae strains isolated from children showed higher resistance rate than the strains isolated from adults.Overall,779 strains of H.influenzae did not produce β-lactamase but were resistant to ampicillin(BLNAR).Beta-lactamase-producing strains showed significantly higher resistance rates to these antimicrobial agents than the β-lactamase-nonproducing strains.Of the 16 191 M.catarrhalis strains,80.06%were isolated from children and 19.94%isolated from adults.M.catarrhalis strains were mostly susceptible to both amoxicillin-clavulanic acid and cefuroxime,evidenced by resistance rate lower than 2.0%.Conclusions The emergence of antibiotic-resistant H.influenzae due to β-lactamase production poses a challenge for clinical anti-infective treatment.Therefore,it is very important to implement antibiotic resistance surveillance for H.influenzae and guide rational antibiotic use.All local clinical microbiology laboratories should actively improve antibiotic susceptibility testing and strengthen antibiotic resistance surveillance for H.influenzae.
8.Psychometric validation of the Chinese version of the Vascular Quality of Life Questionnaire-6
Jiali HU ; Yanghui XU ; Xuefang HUANG ; Ya MENG ; Yanqing LI ; Zhifeng GU
Chinese Journal of Modern Nursing 2025;31(21):2815-2821
Objective:To translate the Vascular Quality of Life Questionnaire-6 (VQ6) into a Chinese version and to test its reliability and validity in patients with peripheral arterial disease.Methods:The English version of VQ6 scale was sinicized following the Brislin translation guidelines, and the Delphi consultation was used for cultural debugging to form the Chinese version of the VQ6. Convenience sampling was used to select 146 patients with peripheral arterial disease who attended the Department of Interventional and Vascular Surgery and the Department of Endocrinology of Affiliated Hospital of Nantong University from May to June 2024 for the survey. Data were analyzed using SPSS 26.0 and Amos 26.0. Correlation analysis and critical ratio method were used for item analysis and content validity index was used to evaluate content validity. The Chinese version of the Patient-Reported Outcomes Measurement Information System 29 Profile V2.1 (PROMIS-29 Profile v2.1) was selected as a validity scale to evaluate the criterion-related validity. Exploratory factor analysis and confirmatory factor analysis were used to evaluate the structural validity of the scale, and transgender test was used for measurement equivalence. Reliability of the scale was evaluated with the Cronbach's α coefficient and retest reliability index.Results:The Chinese version of the VQ6 scale had six items. The scale-level content validity index was 0.972, and the item-level content validity index ranged from 0.833 to 1.000. One common factor was extracted with a cumulative variance contribution of 83.526%. Criterion-related validity showed that the correlation coefficient between the Chinese version of the VQ6 and the PROMIS-29 Profile v2.1 was 0.688 ( P<0.01) . The scale essentially satisfied Δ RMSEA < 0.015 and Δ CFI < 0.01 in the transgender equivalence test. The Cronbach's α coefficient for the scale was 0.968 and the retest reliability was 0.978. Conclusions:The Chinese version of the VQ6 has good reliability and validity and is suitable as an assessment tool for quality of life in patients with peripheral arterial disease in our cultural context.
9.Mechanism of Treatment of Hepatocellular Carcinoma with Traditional Chinese Medicine Based on Epigenetic Regulation: A Review
Xianyu XU ; Yongping ZHU ; Yanqing LIU ; Liwei GU ; Junzhe ZHANG ; Shengnan SHEN ; Jigang WANG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(23):281-291
Hepatocellular carcinoma (HCC) is the sixth most common cancer in the world. In recent years, the clinical early diagnosis and treatment protocols of HCC have been improved, whereas the prognosis of patients is still not satisfactory, which is due to the fact that the mechanism of HCC development has not been fully elucidated. Therefore, it is of great significance to explore the molecular mechanisms and key regulatory links of hepatocellular carcinoma development to further improve the diagnosis and treatment of HCC in China. Epigenetics has become a research hotspot because of its reversibility and easy regulation. According to relevant studies, HCC involves the accumulation of multiple genetic and epigenetic changes during the initiation, promotion, and progression stages. HCC is categorized as infantile malnutrition with accumulation, hypochondriac pain, tympan ites, and abdominal mass in traditional Chinese medicine (TCM). In the treatment of HCC, TCM with low toxicity, multi-targets, and multi-mechanisms can inhibit tumor growth, alleviate the clinical symptoms, and enhance the quality of life of the patients. Chinese medicines and their active ingredients exert anti-HCC effects through epigenetic regulation of DNA methylation, histone modification, and non-coding RNA. Abnormal gene expression due to epigenetic regulation disorders is involved in all stages of HCC development. There are few studies on epigenetic regulation in TCM treatment of HCC, and there is still much room for development in basic and clinical trials. This paper reviews the mechanism of epigenetic regulation in HCC and summarizes the experimental results of TCM research on the related mechanism, with a view to providing a theoretical basis for future research on the mechanism of HCC development and clinical diagnosis and treatment of hepatocellular carcinoma with TCM.
10.A novel shark VNAR antibody-based immunotoxin targeting TROP-2 for cancer therapy.
Xiaozhi XI ; Yanqing WANG ; Guiqi AN ; Shitao FENG ; Qiumei ZHU ; Zhongqiu WU ; Jin CHEN ; Zhicheng ZUO ; Qiang WANG ; Ming-Wei WANG ; Yuchao GU
Acta Pharmaceutica Sinica B 2024;14(11):4806-4818
TROP-2, a tumor-associated antigen, has been implicated in the progression of various epithelial tumors. Due to its favorable expression profile, TROP-2 has emerged as a promising target for antibody-drug conjugates (ADCs) based anti-tumor therapies. Although ADCs have shown efficacy in cancer treatment, their application in solid tumors is hindered by their high molecular weight, poor tumor penetration, and release of cytotoxic molecules. Therefore, a recombinant immunotoxin was developed based on a shark-derived variable domain of immunoglobulin new antigen receptor (VNAR) antibody. VNARs are only one-tenth the size of IgG antibodies and possess remarkable tissue penetration capabilities and high stability. In this study, a shark VNAR phage display library was created, leading to the identification of shark VNAR-5G8 that targets TROP-2. VNAR-5G8 exhibited a high affinity and cellular internalization ability towards cells expressing high levels of TROP-2. Epitope analysis revealed that VNAR-5G8 recognizes a hidden epitope consisting of CRD and TY-1 on TROP-2. Subsequently, VNAR-5G8 was fused with a truncated form of Pseudomonas exotoxin (PE38) to create the recombinant immunotoxin (5G8-PE38), which exhibited significant anti-tumor activity in vitro and in vivo. Overall, this study highlights the promise of 5G8-PE38 as a valuable candidate for cancer therapy.

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