1.A novel dual-targeting strategy of nanobody-driven protein corona modulation for glioma therapy.
Yupei ZHANG ; Shugang QIN ; Tingting SONG ; Zhiying HUANG ; Zekai LV ; Yang ZHAO ; Xiangyu JIAO ; Min SUN ; Yinghan ZHANG ; Guang XIE ; Yuting CHEN ; Xuli RUAN ; Ruyue LIU ; Haixing SHI ; Chunli YANG ; Siyu ZHAO ; Zhongshan HE ; Hai HUANG ; Xiangrong SONG
Acta Pharmaceutica Sinica B 2025;15(9):4917-4931
Glioma represents the most prevalent malignant tumor of the central nervous system, with chemotherapy serving as an essential adjunctive treatment. However, most chemotherapeutic agents exhibit limited ability to penetrate the blood-brain barrier (BBB). This study introduced a novel dual-targeting strategy for glioma therapy by modulating the formation of nanobody-driven protein coronas to enhance the brain and tumor-targeting efficiency of hydrophobic cisplatin prodrug-loaded lipid nanoparticles (C8Pt-Ls). Specifically, nanobodies (Nbs) with fibrinogen-binding capabilities were conjugated to the surface of C8Pt-Ls, resulting in the generation of Nb-C8Pt-Ls. Within the bloodstream, Nb-C8Pt-Ls could bound more fibrinogen, forming the protein corona that specifically interacted with LRP-1, a receptor highly expressed on the BBB. This interaction enabled a "Hitchhiking Effect" mechanism, facilitating efficient trans-BBB transport and promoting effective brain targeting. Additionally, the protein corona interacted with LRP-1, which is also overexpressed in glioma cells, achieving precise tumor targeting. Computational simulations and SPR detection clarified the molecular interaction mechanism of the Nb-fibrinogen-(LRP-1) complex, confirming its binding specificity and stability. Our results demonstrated that this strategy significantly enhanced C8Pt accumulation in brain tissues and tumors, induced apoptosis in glioma cells, and improved therapeutic efficacy. This study provides a novel framework for glioma therapy and underscores the potential of protein corona modulation-based dual-targeting strategies in advancing treatments for brain tumors.
2.Development and test of an integrated automatic quality control system for HDR afterloader
Chunli LUO ; Jie ZHANG ; Longtao XIE ; Yuliang SUN ; Lang YU ; Jie QIU
China Medical Equipment 2025;22(5):38-41
Objective:An integrated automatic quality control system(automatic quality control instrument)for high dose rate(HDR)afterloader was independently developed.This system was used to measure the placement accuracy,residence time and activity of the radioactive source,so as to assess the accuracy and stability of this system in quality assurance.Methods:The automatic quality control system was connected to the Flexitron type of HDR afterloader through a connecting tube.Quality assurance(QA)plans with different resident positions,clearances,and times were designed for measurement and verification.The measurement length was 1079-1119 mm,and the measurement time was 2-10 s,and the measurement activity was 14,326-28,653 μGy·m2·h-1.The measurements were repeated once per one week in three months,so as to determine the consistency of the measurement parameters in a longer period of time.The measurement results of the placement accuracy,resident time and activity of radioactive source of the HDR 192Ir radioactive source were analyzed.Results:The plate ionization chamber was used to measure the activity of radioactive source.In three months,the measurement deviation of the activity of radioactive source was 1.17%,and the fitted activity decay curve was consistent with the expected decay curve of radioactive source.The measurement accuracies of the positioning of radioactive source were respectively 0.46,0.18,0.23,0.25,and 0.15 mm when the interval step sizes of resident times were respectively 2,3,5,8,and 10 mm,all of them were<1 mm.The measurement accuracy of time was(4.90±0.04)s when the resident time was 5 s.In the measurement accuracy of different resident times(1,2,3,5 and 10s)of same step size,the deviation of them was less than 0.5s.When the resident time was the shortest,the deviation between the read-out value of the automatic system software of quality control and the actually resident time was(0.09±0.04)s.The measurement accuracy gradually stabilized with the increasing of resident times.Conclusion:The automatic quality control instrument can complete the measurements for the positioning accuracy,the accuracy of resident time and the activity of radioactive source,and achieve rapidly and accurately periodic quality assurance.
3.Screening and validation of tsRNAs associated with lung adenocarcinoma
Chunli LU ; Yifan SHAN ; Weijia XIE ; Tingting XIA ; Ying XIANG ; Na WU ; Long WU ; Li BAI ; Yafei LI
Journal of Army Medical University 2025;47(2):122-131
Objective To explore the roles of transfer RNA-derived small RNAs(tsRNAs)in the oncogenesis and progression of lung adenocarcinoma by analyzing the differential expression of tsRNAs in lung adenocarcinoma and the relationship between the expression levels of tsRNAs in lung adenocarcinoma and the prognosis of patients in order to further screen and validate the tsRNAs associated with lung adenocarcinoma.Methods The differential expression of tsRNAs between lung adenocarcinoma tissues and normal tissues was analyzed based on the database of the Computational Medicine Center.The effects of tsRNAs expression levels on the prognosis of lung adenocarcinoma patients were analyzed based on the Cancer Genome Atlas(TCGA)database(TCGA-LUAD).The target genes were predicted based on TRFtarget2.0 and tRFTar databases.Gene ontology(GO)enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis were performed based on DAVID and KOBA KEGG online websites.The expression levels of target genes in lung adenocarcinoma tissues and normal tissues were analyzed based on the University of ALabama at Birmingham CANcer data analysis Portal(UALCAN)database.In vitro cell proliferation,migration,and invasion assays were performed to investigate the biological functions of tRF-19-69M8LOJX in lung adenocarcinoma cells.Results Compared with the normal tissues,tRF-19-69M8LOJX was up-regulated in lung adenocarcinoma tissues(log2FC=4.28,FDR<0.05).High expression level of tRF-19-69M8LOJX was associated with shorter progression-free survival(HR=1.565,95%CI=1.142-2.145,P=0.005).And its overexpression promoted cell proliferation and migration(P<0.001),and invasion(P=0.009)of A549 cells,and up-regulated COL1A1(P=0.002)and VCAN(P=0.022)significantly in the tRF-19-69M8LOJX overexpression cell model.Conclusion tRF-19-69M8LOJX is up-regulated in lung adenocarcinoma tissues.And its high expression is closely associated with poor prognosis.The tsRNA may play an important role in the pathogenesis and development of lung adenocarcinoma.
4.Robotic-assisted versus laparoscopic Nissen fundoplication in the treatment of gastroesophageal refux disease: a comparative analysis of surgical advantages and short-term outcomes
Ziwen WEI ; Xiaoyu LIU ; Chunli ZOU ; Rujuan WANG ; Yongyi XIE ; Dingwei LU ; Honglin YI ; Yuewen ZHANG ; Ruhong LI ; Peng LI
Chinese Journal of General Surgery 2025;40(6):439-444
Objective:To evaluate the advantages and short-term clinical effects of totally robotic Nissen 360° fundoplication compared with laparoscopic surgery.Methods:A retrospective analysis was conducted on data of 110 patients undergoing Nissen 360° fundoplication at the Second Department of General Surgery, Yan'an Hospital Affiliated to Kunming Medical University from Aug 2023 to Aug 2024. Among them, 50 cases underwent totally robotic fundoplication, and 60 cases underwent laparoscopic fundoplication. By comparing and analyzing the fatigue level of the primary surgeon during the operations, postoperative incisional pain in patients, swallowing function recovery and the time to resume a normal solid-food diet within 3 months post-surgery, the advantages of totally robotic surgery were evaluated. Additionally, by examining the postoperative recovery of reflux symptoms, postoperative patient comfort, and satisfaction levels in both groups, the short-term clinical outcomes of totally robotic surgery were assessed.Results:Both groups of patients successfully completed the surgeries without any intraoperative or postoperative complications occurring. The fatigue score of the primary surgeon in the totally robotic group was significantly better than that in the laparoscopic group[ (2.34±1.38) vs. (2.89±1.51), t=1.385, P<0.01]. The time taken to resume a normal solid-food diet postoperatively in the totally robotic group was significantly shorter than that in the laparoscopic group[ (27.90±6.77) d vs. (40.78±13.60) d, t =5.765, P<0.01]. Moreover, the postoperative pain comfort level was better in the robotic group than in the laparoscopic group [(1.65±0.72) points vs. (2.23±0.59) points, t=3.742, P<0.01]. Within 12 months postoperatively, the GERD-Q scores in the totally robotic group decreased significantly, and reflux symptoms disappeared, comparable to that in the laparoscopic group. Conclusions:The totally robotic Nissen 360° fundoplication leads to lower fatigue levels for the surgeon. Patients experience significant advantages in terms of postoperative pain perception and dietary recovery. Additionally, it demonstrates excellent postoperative anti-reflux efficacy, high patient comfort, and the surgery is safe and reliable.
5.Established cell model and mechanism of visceral hypersensitivity and nerve hyperplasia in IBS using P815 and N2a co-culture
Hongbin LI ; Chunli GAN ; Xiangyu XIE ; Shan LIU ; Qin LU ; Wei KE ; Shi-yu QI ; Yusheng HUANG ; Hongmei TANG
Chinese Journal of Pathophysiology 2025;41(4):825-832
AIM:To establish a cell model of visceral hypersensitivity and nerve hyperplasia in irritable bowel syndrome(IBS)by conducting an in vitro co-culture of mouse P815 mast cells and N2a nerve cells and explore its possible mechanism.METHODS:Enzyme-linked immunosorbent assay(ELISA)with three replicates was used to confirm the C48/80-induced P815 degranulation.The length of neurites was observed under bright field microscopy to determine the number of differentiated neurons,thereby selecting the concentration of retinoic acid(RA)for stimulating the differentia-tion of N2a cells,with four replicates.A co-culture system of P815 and N2a cells was established using Transwell cham-bers with four replicates.The following groups were established:N2a cells cultured alone,N2a cells co-cultured with P815 cells,N2a cells co-cultured with P815 cells plus C48/80,and N2a cells plus RA group.After co-culturing,the num-ber of differentiated N2a cells was observed under bright field.The expression of nerve growth factor(NGF),tyrosine ki-nase receptor A(TRKA),growth-associated protein-43(GAP43),neuron-specific enolase(NSE),synapsin(SYN),and postsynaptic density protein-95(PSD-95)at both protein and gene levels in N2a cells was detected using Western blot and polymerase chain reaction(PCR),with four replicates.RESULTS:The best condition for N2a differentiation was stimulation with 10 μmol/L RA for 24 hours,whereas the best condition for degranulation was stimulation of P815 cells with 20 mg/L C48/80 for 24 hours.Compared with N2a cells cultured alone,the differentiation ratio of the N2a+P815+C48/80 and N2a+RA groups was significantly increased(P<0.01),and the protein and mRNA expressions of NGF,TRKA,GAP43,NSE,SYN,and PSD-95 were significantly increased(P<0.05).CONCLUSION:Our results revealed that mast cell degranulation enhances the level of nerve hyperplasia in enteric nerve cells and promotes changes in nerve structure and function.Synaptic remodeling regulated by abnormal expression of key proteins such as NGF,TRKA,and GAP43 is involved in the nerve hyperplasia induced by mast cell degranulation.
6.Surveillance and early warning index system for schistosomiasis in the middle and lower reaches of the Yangtze River basin
Sanhong JIANG ; Yibiao ZHOU ; Shizhu LI ; Dandan LIN ; Qingwu JIANG ; Liyong WEN ; Shengming LI ; Fei HU ; Benjiao HU ; Jie ZHOU ; Chunli CAO ; Jing XU ; Jianwen XIE ; Changming WU ; Xiaolan YAN ; Weimin XU ; Jun GE ; Guanghui REN ; Xiaoli LIU
Chinese Journal of Endemiology 2025;44(4):259-264
Under the current situation of "low prevalence and low infection" of schistosomiasis in China, and to provide a basis for achieving the goal of eliminating schistosomiasis by 2030 proposed by the Healthy China Action (2019 - 2030) as scheduled, the Hunan Provincial Corps Hospital of the Chinese People's Armed Police Force established a schistosomiasis monitoring and early warning index system based on the previous studies on schistosomiasis early warning index system and the recent literature analysis, combined with the current potential risk factors affecting the transmission and prevalence of schistosomiasis, and organized two rounds of expert consultation and carried out project promotion meetings. The experts reached a consensus on the comprehensiveness and practicability of the index system, aiming to lay a solid foundation for construction of China's schistosomiasis prevention and control early warning system.
7.Surveillance and early warning index system for schistosomiasis in the middle and lower reaches of the Yangtze River basin
Sanhong JIANG ; Yibiao ZHOU ; Shizhu LI ; Dandan LIN ; Qingwu JIANG ; Liyong WEN ; Shengming LI ; Fei HU ; Benjiao HU ; Jie ZHOU ; Chunli CAO ; Jing XU ; Jianwen XIE ; Changming WU ; Xiaolan YAN ; Weimin XU ; Jun GE ; Guanghui REN ; Xiaoli LIU
Chinese Journal of Endemiology 2025;44(4):259-264
Under the current situation of "low prevalence and low infection" of schistosomiasis in China, and to provide a basis for achieving the goal of eliminating schistosomiasis by 2030 proposed by the Healthy China Action (2019 - 2030) as scheduled, the Hunan Provincial Corps Hospital of the Chinese People's Armed Police Force established a schistosomiasis monitoring and early warning index system based on the previous studies on schistosomiasis early warning index system and the recent literature analysis, combined with the current potential risk factors affecting the transmission and prevalence of schistosomiasis, and organized two rounds of expert consultation and carried out project promotion meetings. The experts reached a consensus on the comprehensiveness and practicability of the index system, aiming to lay a solid foundation for construction of China's schistosomiasis prevention and control early warning system.
8.Development and test of an integrated automatic quality control system for HDR afterloader
Chunli LUO ; Jie ZHANG ; Longtao XIE ; Yuliang SUN ; Lang YU ; Jie QIU
China Medical Equipment 2025;22(5):38-41
Objective:An integrated automatic quality control system(automatic quality control instrument)for high dose rate(HDR)afterloader was independently developed.This system was used to measure the placement accuracy,residence time and activity of the radioactive source,so as to assess the accuracy and stability of this system in quality assurance.Methods:The automatic quality control system was connected to the Flexitron type of HDR afterloader through a connecting tube.Quality assurance(QA)plans with different resident positions,clearances,and times were designed for measurement and verification.The measurement length was 1079-1119 mm,and the measurement time was 2-10 s,and the measurement activity was 14,326-28,653 μGy·m2·h-1.The measurements were repeated once per one week in three months,so as to determine the consistency of the measurement parameters in a longer period of time.The measurement results of the placement accuracy,resident time and activity of radioactive source of the HDR 192Ir radioactive source were analyzed.Results:The plate ionization chamber was used to measure the activity of radioactive source.In three months,the measurement deviation of the activity of radioactive source was 1.17%,and the fitted activity decay curve was consistent with the expected decay curve of radioactive source.The measurement accuracies of the positioning of radioactive source were respectively 0.46,0.18,0.23,0.25,and 0.15 mm when the interval step sizes of resident times were respectively 2,3,5,8,and 10 mm,all of them were<1 mm.The measurement accuracy of time was(4.90±0.04)s when the resident time was 5 s.In the measurement accuracy of different resident times(1,2,3,5 and 10s)of same step size,the deviation of them was less than 0.5s.When the resident time was the shortest,the deviation between the read-out value of the automatic system software of quality control and the actually resident time was(0.09±0.04)s.The measurement accuracy gradually stabilized with the increasing of resident times.Conclusion:The automatic quality control instrument can complete the measurements for the positioning accuracy,the accuracy of resident time and the activity of radioactive source,and achieve rapidly and accurately periodic quality assurance.
9.Established cell model and mechanism of visceral hypersensitivity and nerve hyperplasia in IBS using P815 and N2a co-culture
Hongbin LI ; Chunli GAN ; Xiangyu XIE ; Shan LIU ; Qin LU ; Wei KE ; Shi-yu QI ; Yusheng HUANG ; Hongmei TANG
Chinese Journal of Pathophysiology 2025;41(4):825-832
AIM:To establish a cell model of visceral hypersensitivity and nerve hyperplasia in irritable bowel syndrome(IBS)by conducting an in vitro co-culture of mouse P815 mast cells and N2a nerve cells and explore its possible mechanism.METHODS:Enzyme-linked immunosorbent assay(ELISA)with three replicates was used to confirm the C48/80-induced P815 degranulation.The length of neurites was observed under bright field microscopy to determine the number of differentiated neurons,thereby selecting the concentration of retinoic acid(RA)for stimulating the differentia-tion of N2a cells,with four replicates.A co-culture system of P815 and N2a cells was established using Transwell cham-bers with four replicates.The following groups were established:N2a cells cultured alone,N2a cells co-cultured with P815 cells,N2a cells co-cultured with P815 cells plus C48/80,and N2a cells plus RA group.After co-culturing,the num-ber of differentiated N2a cells was observed under bright field.The expression of nerve growth factor(NGF),tyrosine ki-nase receptor A(TRKA),growth-associated protein-43(GAP43),neuron-specific enolase(NSE),synapsin(SYN),and postsynaptic density protein-95(PSD-95)at both protein and gene levels in N2a cells was detected using Western blot and polymerase chain reaction(PCR),with four replicates.RESULTS:The best condition for N2a differentiation was stimulation with 10 μmol/L RA for 24 hours,whereas the best condition for degranulation was stimulation of P815 cells with 20 mg/L C48/80 for 24 hours.Compared with N2a cells cultured alone,the differentiation ratio of the N2a+P815+C48/80 and N2a+RA groups was significantly increased(P<0.01),and the protein and mRNA expressions of NGF,TRKA,GAP43,NSE,SYN,and PSD-95 were significantly increased(P<0.05).CONCLUSION:Our results revealed that mast cell degranulation enhances the level of nerve hyperplasia in enteric nerve cells and promotes changes in nerve structure and function.Synaptic remodeling regulated by abnormal expression of key proteins such as NGF,TRKA,and GAP43 is involved in the nerve hyperplasia induced by mast cell degranulation.
10.Robotic-assisted versus laparoscopic Nissen fundoplication in the treatment of gastroesophageal refux disease: a comparative analysis of surgical advantages and short-term outcomes
Ziwen WEI ; Xiaoyu LIU ; Chunli ZOU ; Rujuan WANG ; Yongyi XIE ; Dingwei LU ; Honglin YI ; Yuewen ZHANG ; Ruhong LI ; Peng LI
Chinese Journal of General Surgery 2025;40(6):439-444
Objective:To evaluate the advantages and short-term clinical effects of totally robotic Nissen 360° fundoplication compared with laparoscopic surgery.Methods:A retrospective analysis was conducted on data of 110 patients undergoing Nissen 360° fundoplication at the Second Department of General Surgery, Yan'an Hospital Affiliated to Kunming Medical University from Aug 2023 to Aug 2024. Among them, 50 cases underwent totally robotic fundoplication, and 60 cases underwent laparoscopic fundoplication. By comparing and analyzing the fatigue level of the primary surgeon during the operations, postoperative incisional pain in patients, swallowing function recovery and the time to resume a normal solid-food diet within 3 months post-surgery, the advantages of totally robotic surgery were evaluated. Additionally, by examining the postoperative recovery of reflux symptoms, postoperative patient comfort, and satisfaction levels in both groups, the short-term clinical outcomes of totally robotic surgery were assessed.Results:Both groups of patients successfully completed the surgeries without any intraoperative or postoperative complications occurring. The fatigue score of the primary surgeon in the totally robotic group was significantly better than that in the laparoscopic group[ (2.34±1.38) vs. (2.89±1.51), t=1.385, P<0.01]. The time taken to resume a normal solid-food diet postoperatively in the totally robotic group was significantly shorter than that in the laparoscopic group[ (27.90±6.77) d vs. (40.78±13.60) d, t =5.765, P<0.01]. Moreover, the postoperative pain comfort level was better in the robotic group than in the laparoscopic group [(1.65±0.72) points vs. (2.23±0.59) points, t=3.742, P<0.01]. Within 12 months postoperatively, the GERD-Q scores in the totally robotic group decreased significantly, and reflux symptoms disappeared, comparable to that in the laparoscopic group. Conclusions:The totally robotic Nissen 360° fundoplication leads to lower fatigue levels for the surgeon. Patients experience significant advantages in terms of postoperative pain perception and dietary recovery. Additionally, it demonstrates excellent postoperative anti-reflux efficacy, high patient comfort, and the surgery is safe and reliable.

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