AIM: To investigate the antitumor activity of adriamycin (ADR) encapsulated in nanoparticles (NADR) and injected into the hepatic artery of hepatoma-bearing rats.METHODS: NADR was prepared by the interfacial polymeriz...AIM: To investigate the antitumor activity of adriamycin (ADR) encapsulated in nanoparticles (NADR) and injected into the hepatic artery of hepatoma-bearing rats.METHODS: NADR was prepared by the interfacial polymerization method. Walker-256 carcinosarcomas were surgically implanted into the left liver lobes of 60 male Wistar rats, which were divided into 4 groups at random (15 rats per group). On the 7th day after implantation, normal saline (NS), free ADR (FADR), NADR, or ADR mixed with unloaded nanoparticles (ADR+NP) was respectively injected via the hepatic artery (i.a.) of rats in different groups. The dose of ADR in each formulation was 2.0 mg/kg body weight and the concentration was 1.0 mg/mL. Survival time, tumor enlargement ratio, and tumor necrosis degree were compared between each group.RESULTS: Compared with the rats that received NS i.a.,the rats that received FADR or ADR+NP acquired apparent inhibition on tumor growth, as well as prolonged their life span. Further significant anticancer efficacy was observed in rats that received i.a. administration of NADR. Statistics indicated that NADR brought on a more significant tumor inhibition and more extensive tumor necrosis, as compared to FADR or ADR+NP. The mean tumor enlargement ratio on the 7th day after NADR i.a. was 1.106. The mean tumorbearing survival time was 39.50 days. Prolonged life span ratio was 109.22% as compared with rats that accepted NS.CONCLUSION: Therapeutic effect of ADR on liver malignancy can be significantly enhanced by its nanopaticle formulation and administration via hepatic artery.展开更多
AIM:Quasispecies of hepatitis C virus (HCV) are the foundation for rapid sequence evolution of HCV to evade immune surveillance of hosts. The consensus sequence evolution of a segment of HCV NS3 region, which encompas...AIM:Quasispecies of hepatitis C virus (HCV) are the foundation for rapid sequence evolution of HCV to evade immune surveillance of hosts. The consensus sequence evolution of a segment of HCV NS3 region, which encompasses putative cytotoxic T cell epitopes,was evaluated.METHODS:Three male patients, infected with HCV through multiple transfusions,were identified from clinical symptoms and monitored by aminotransferase for 60 months.Blood samples taken at months 0, 32, and 60 were used for viral RNA extraction. A segment of HCV NS3 region was amplified from the RNA extraction by RT-PCR and subjected to subcloning and sequencing.HLA types of these three patients were determined using complement-dependent microlymphocytotoxic assay. CTL epitopes were predicted using MHC binding motifs.RESULTS:No patient had clinical symptoms or elevation of aspartate/alanine arninotransferase. Two patients showed positive HCV PCR results at all 3 time points. The other one showed a positive HCV PCR result only at month 0.A reported HLA-A2-restricted CTL epitope had no alteration in the HLA-A2-negative carrier over 60 months.In the HLA-A2-positive individuals, all the sequences from 0 month 0 showed an amber mutation on the initial codon of the epitope. Most changes of consensus sequences in the same patient occurred on predicted cytotoxic T cell epitopes.CONCLUSION:Amber mutation and changes of consensus sequence in HCV NS3 region may be related to viral immune escape.展开更多
Background:Anaplastic lymphoma kinase(ALK)test in advanced non-small cell lung cancer(NSCLC)can help physicians provide target therapies for patients harboring ALK gene rearrangement.This study aimed to investigate th...Background:Anaplastic lymphoma kinase(ALK)test in advanced non-small cell lung cancer(NSCLC)can help physicians provide target therapies for patients harboring ALK gene rearrangement.This study aimed to investigate the real-world test patterns and positive rates of ALK gene rearrangements in advanced NSCLC.Methods:In this real-world study(ChiCTR2000030266),patientswith advanced NSCLC who underwent an ALK rearrangement test in 30 medical centers in China between October 1,2018 and December 31,2019 were retrospectively analyzed.Interpretation training was conducted before the study was initiated.Quality controls were performed at participating centers using immunohistochemistry(IHC)-VENTANA-D5F3.The positive ALK gene rearrangement rate and consistency rate were calculated.The associated clinicopathological characteristics of ALK gene rearrangement were investigated as well.Results:The overall ALK gene rearrangement rate was 6.7%in 23,689 patients with advanced NSCLC and 8.2%in 17,436 patients with advanced lung adenocarcinoma.The quality control analysis of IHC-VENTANA-D5F3 revealed an intrahospital consistency rate of 98.2%(879/895)and an inter-hospital consistency rate of 99.2%(646/651).IHC-VENTANA-D5F3 was used in 53.6%,real-time polymerase chain reaction(RT-PCR)in 25.4%,next-generation sequencing(NGS)in 18.3%,and fluorescence in-situ hybridization(FISH)in 15.9%in the adenocarcinoma subgroup.For specimens tested with multiple methods,the consistency rates confirmed by IHC-VENTANA-D5F3 were 98.0%(822/839)for FISH,98.7%(1,222/1,238)forNGS,and 91.3%(146/160)for RT-PCR.The overall ALK gene rearrangement rateswere higher in females,patients of≤35 years old,never smokers,tumor cellularity of>50,and metastatic specimens used for testing in the total NSCLC population and adenocarcinoma subgroup(all P<0.05).Conclusions:This study highlights the real-world variability and challenges of ALK test in advanced NSCLC,demonstrating a predominant use of IHCVENTANA-D5F3 with high consistency and distinct clinicopathological features in ALK-positive patients.These findings underscore the need for a consensus on optimal test practices and support the development of refined ALK test strategies to enhance diagnostic accuracy and therapeutic decision-making in NSCLC.展开更多
In the field of proton exchange membranes(PEMs),it is still a great challenge to explore new Nafion alternatives,maintaining the high proton conductivity and lowering the cost of practical application.In this work,a s...In the field of proton exchange membranes(PEMs),it is still a great challenge to explore new Nafion alternatives,maintaining the high proton conductivity and lowering the cost of practical application.In this work,a series of low sulfonated poly(aryl ether ketone sulfone)(SPAEKS)membranes hybridized by[Bi_(6)O_(5)(OH)_(3)]_(2)(NO_(3))10⋅6H_(2)O(H_(6)Bi_(12)O_(16))have been successfully fabricated.When the doping amount of H6Bi12O16 reaches 5 wt%,the DS15-Bi12-5 showing the best proton conductive ability and mechanical properties.The proton conductivity can achieve 72.8 mS⋅cm−1 at 80℃ and the tensile strength can reach 43.57 MPa.Confirmed by experimental data and activation energy(Ea)calculations,the existence of Bi cluster makes more hydrogen bonds,providing additional proton hopping sites and offers more proton transport vehicles,leading to a high proton conduction performance.This work proved that polyoxometalates(POMs)can replace the role of sulfonate groups in SPAEKS to a certain extent and work out the defects of high sulfonation,making a remarkable contribution to the practical application of low sulfonated SPAEKS.展开更多
文摘AIM: To investigate the antitumor activity of adriamycin (ADR) encapsulated in nanoparticles (NADR) and injected into the hepatic artery of hepatoma-bearing rats.METHODS: NADR was prepared by the interfacial polymerization method. Walker-256 carcinosarcomas were surgically implanted into the left liver lobes of 60 male Wistar rats, which were divided into 4 groups at random (15 rats per group). On the 7th day after implantation, normal saline (NS), free ADR (FADR), NADR, or ADR mixed with unloaded nanoparticles (ADR+NP) was respectively injected via the hepatic artery (i.a.) of rats in different groups. The dose of ADR in each formulation was 2.0 mg/kg body weight and the concentration was 1.0 mg/mL. Survival time, tumor enlargement ratio, and tumor necrosis degree were compared between each group.RESULTS: Compared with the rats that received NS i.a.,the rats that received FADR or ADR+NP acquired apparent inhibition on tumor growth, as well as prolonged their life span. Further significant anticancer efficacy was observed in rats that received i.a. administration of NADR. Statistics indicated that NADR brought on a more significant tumor inhibition and more extensive tumor necrosis, as compared to FADR or ADR+NP. The mean tumor enlargement ratio on the 7th day after NADR i.a. was 1.106. The mean tumorbearing survival time was 39.50 days. Prolonged life span ratio was 109.22% as compared with rats that accepted NS.CONCLUSION: Therapeutic effect of ADR on liver malignancy can be significantly enhanced by its nanopaticle formulation and administration via hepatic artery.
文摘AIM:Quasispecies of hepatitis C virus (HCV) are the foundation for rapid sequence evolution of HCV to evade immune surveillance of hosts. The consensus sequence evolution of a segment of HCV NS3 region, which encompasses putative cytotoxic T cell epitopes,was evaluated.METHODS:Three male patients, infected with HCV through multiple transfusions,were identified from clinical symptoms and monitored by aminotransferase for 60 months.Blood samples taken at months 0, 32, and 60 were used for viral RNA extraction. A segment of HCV NS3 region was amplified from the RNA extraction by RT-PCR and subjected to subcloning and sequencing.HLA types of these three patients were determined using complement-dependent microlymphocytotoxic assay. CTL epitopes were predicted using MHC binding motifs.RESULTS:No patient had clinical symptoms or elevation of aspartate/alanine arninotransferase. Two patients showed positive HCV PCR results at all 3 time points. The other one showed a positive HCV PCR result only at month 0.A reported HLA-A2-restricted CTL epitope had no alteration in the HLA-A2-negative carrier over 60 months.In the HLA-A2-positive individuals, all the sequences from 0 month 0 showed an amber mutation on the initial codon of the epitope. Most changes of consensus sequences in the same patient occurred on predicted cytotoxic T cell epitopes.CONCLUSION:Amber mutation and changes of consensus sequence in HCV NS3 region may be related to viral immune escape.
基金CAMS Innovation Fund for Medical Sciences,Grant/Award Numbers:2021-1-I2M-012,2022-I2M-C&T-B-078Beijing Hope Run Special Fund of Cancer Foundation of the People’s Republic of China,Grant/Award Number:LC2019L04+1 种基金National Key Research and Development Program,Grant/Award Number:2022YFC2409902Capital’s Funds for Health Improvement and Research,Grant/Award Number:2020-2Z-4028。
文摘Background:Anaplastic lymphoma kinase(ALK)test in advanced non-small cell lung cancer(NSCLC)can help physicians provide target therapies for patients harboring ALK gene rearrangement.This study aimed to investigate the real-world test patterns and positive rates of ALK gene rearrangements in advanced NSCLC.Methods:In this real-world study(ChiCTR2000030266),patientswith advanced NSCLC who underwent an ALK rearrangement test in 30 medical centers in China between October 1,2018 and December 31,2019 were retrospectively analyzed.Interpretation training was conducted before the study was initiated.Quality controls were performed at participating centers using immunohistochemistry(IHC)-VENTANA-D5F3.The positive ALK gene rearrangement rate and consistency rate were calculated.The associated clinicopathological characteristics of ALK gene rearrangement were investigated as well.Results:The overall ALK gene rearrangement rate was 6.7%in 23,689 patients with advanced NSCLC and 8.2%in 17,436 patients with advanced lung adenocarcinoma.The quality control analysis of IHC-VENTANA-D5F3 revealed an intrahospital consistency rate of 98.2%(879/895)and an inter-hospital consistency rate of 99.2%(646/651).IHC-VENTANA-D5F3 was used in 53.6%,real-time polymerase chain reaction(RT-PCR)in 25.4%,next-generation sequencing(NGS)in 18.3%,and fluorescence in-situ hybridization(FISH)in 15.9%in the adenocarcinoma subgroup.For specimens tested with multiple methods,the consistency rates confirmed by IHC-VENTANA-D5F3 were 98.0%(822/839)for FISH,98.7%(1,222/1,238)forNGS,and 91.3%(146/160)for RT-PCR.The overall ALK gene rearrangement rateswere higher in females,patients of≤35 years old,never smokers,tumor cellularity of>50,and metastatic specimens used for testing in the total NSCLC population and adenocarcinoma subgroup(all P<0.05).Conclusions:This study highlights the real-world variability and challenges of ALK test in advanced NSCLC,demonstrating a predominant use of IHCVENTANA-D5F3 with high consistency and distinct clinicopathological features in ALK-positive patients.These findings underscore the need for a consensus on optimal test practices and support the development of refined ALK test strategies to enhance diagnostic accuracy and therapeutic decision-making in NSCLC.
基金NationalNatural Science Foundation of China,Grant/Award Numbers:21701016,51803011Science and Technology Development Planning of Jilin Province,Grant/Award Number:20190103129JH+2 种基金Education Department of Jilin Province,Grant/Award Number:JJKH20200666KJChina Scholarship Council,Grant/Award Number:201802335014Welch Foundation,Grant/Award Number:B-0027。
文摘In the field of proton exchange membranes(PEMs),it is still a great challenge to explore new Nafion alternatives,maintaining the high proton conductivity and lowering the cost of practical application.In this work,a series of low sulfonated poly(aryl ether ketone sulfone)(SPAEKS)membranes hybridized by[Bi_(6)O_(5)(OH)_(3)]_(2)(NO_(3))10⋅6H_(2)O(H_(6)Bi_(12)O_(16))have been successfully fabricated.When the doping amount of H6Bi12O16 reaches 5 wt%,the DS15-Bi12-5 showing the best proton conductive ability and mechanical properties.The proton conductivity can achieve 72.8 mS⋅cm−1 at 80℃ and the tensile strength can reach 43.57 MPa.Confirmed by experimental data and activation energy(Ea)calculations,the existence of Bi cluster makes more hydrogen bonds,providing additional proton hopping sites and offers more proton transport vehicles,leading to a high proton conduction performance.This work proved that polyoxometalates(POMs)can replace the role of sulfonate groups in SPAEKS to a certain extent and work out the defects of high sulfonation,making a remarkable contribution to the practical application of low sulfonated SPAEKS.