Objective:Chimeric antigen receptor T-cell(CAR-T)immunotherapy has made major breakthroughs in the treatment of blood tu-mors.However,current CAR-T therapies face several limitations:they require autologous cells,involve a lengthy and costly production pro-cess,and use lentiviral transduction that carry risk of insertional carcinogenesis due to random integration.Therefore,there is an urgent need to develop a universal cost-effective cancer immunotherapy method generating CAR-T cells for in vivo cancer immunotherapy.Meth-ods:This study successfully established an exosome-mediated,T-cell targeted delivery system,demonstrating both precise design and func-tional efficacy for biomedical applications.To optimize CAR-T cell generation the transfection dose was adjusted,and the kinetics of CAR-T cell percentage were recorded.The cytotoxicity of the resulting CAR-T cells was evaluated in vitro by calcein-AM release.To test the tumor-killing in vivo of engineered exosomes,human PBMCs were injected into NPG mice via the tail vein to establish humanized mice,followed by intravenous injection of tumor cells to induce cancer.Results:To overcome the limitations of conditional autologous CAR-T cells,we de-veloped a T cell-targeted exosome system capable of specifically targeting human CD3+,CD4+,and CD8+T cells.CAR-T production was dose-dependent,with transfection efficiency reaching upto 97.8%at 106 particles/cell.Both in vitro cytotoxicity assays and in vivo animal experi-ments demonstrated that exosome-incubated CAR-T cells effectively eliminated CD19-positive Raji cells,highlighting their specificity and therapeutic potential in antigen-directed applications.Conclusions:We successfully established a CD8-targeting exosome delivery system for CAR-T cell production capable of transforming CD8+T cells into functional CAR-T cells,which showed significant tumor-killing ability in vitro and in mice.Compared with the traditional lentiviral vector for the preparation of CAR-T cells in vitro,in vivo-reprogrammed CAR-T cells us-ing our CD8-targeted exosome delivery system,with higher transfection efficiency,shorter production period,lower cost,and eliminated the risk of insertion carcinogenesis.This strategy promises to bring a new era of universal CAR-T medicine,which can improve cancer immuno-therapy and may hold promise as a therapeutic platform to treat various diseases.

Objective:Chimeric antigen receptor T-cell(CAR-T)immunotherapy has made major breakthroughs in the treatment of blood tu-mors.However,current CAR-T therapies face several limitations:they require autologous cells,involve a lengthy and costly production pro-cess,and use lentiviral transduction that carry risk of insertional carcinogenesis due to random integration.Therefore,there is an urgent need to develop a universal cost-effective cancer immunotherapy method generating CAR-T cells for in vivo cancer immunotherapy.Meth-ods:This study successfully established an exosome-mediated,T-cell targeted delivery system,demonstrating both precise design and func-tional efficacy for biomedical applications.To optimize CAR-T cell generation the transfection dose was adjusted,and the kinetics of CAR-T cell percentage were recorded.The cytotoxicity of the resulting CAR-T cells was evaluated in vitro by calcein-AM release.To test the tumor-killing in vivo of engineered exosomes,human PBMCs were injected into NPG mice via the tail vein to establish humanized mice,followed by intravenous injection of tumor cells to induce cancer.Results:To overcome the limitations of conditional autologous CAR-T cells,we de-veloped a T cell-targeted exosome system capable of specifically targeting human CD3+,CD4+,and CD8+T cells.CAR-T production was dose-dependent,with transfection efficiency reaching upto 97.8%at 106 particles/cell.Both in vitro cytotoxicity assays and in vivo animal experi-ments demonstrated that exosome-incubated CAR-T cells effectively eliminated CD19-positive Raji cells,highlighting their specificity and therapeutic potential in antigen-directed applications.Conclusions:We successfully established a CD8-targeting exosome delivery system for CAR-T cell production capable of transforming CD8+T cells into functional CAR-T cells,which showed significant tumor-killing ability in vitro and in mice.Compared with the traditional lentiviral vector for the preparation of CAR-T cells in vitro,in vivo-reprogrammed CAR-T cells us-ing our CD8-targeted exosome delivery system,with higher transfection efficiency,shorter production period,lower cost,and eliminated the risk of insertion carcinogenesis.This strategy promises to bring a new era of universal CAR-T medicine,which can improve cancer immuno-therapy and may hold promise as a therapeutic platform to treat various diseases.

Objective Meta-analysis was performed to evaluate the clinical efficacy of fenestration decompression and curettage in the treatment of jaw cyst.Methods Randomized controlled trials comparing fenestration decompression and curettage in treatment of jaw cysts were retrieved from PubMed,Cochrane Library,CNKI,SinoMed,VIP and Wanfang data from built databases to June 2024.A Meta-analysis was performed using RevMan 5.4 software to compare the rate of capsule volume reduction,bone hyperplasia thickness and bone density at 3,6 and 12 months after treatment with two methods.Results A total of 14 literatures were included.At 3,6 and 12 months after operation,rate of capsule volume reduction and bone density after fenestration decompression were significantly better than that after curettage.At 6 and 12 months after operation,bone hyperplasia thickness after fenestration decompression were significantly greater than that after curettage.Conclusion Fenestration decompression is superior to curettage in the treatment of jaw cyst in terms of rate of capsule volume reduction,bone hyperplasia thickness and bone density.

TSCI have dyskinesia and sensory disturbance that can cause various life-threaten complications. The patients with traumatic spinal cord injury (TSCI), seriously affecting the quality of life of patients. Based on the epidemiology of TSCI and domestic and foreign literatures as well as expert investigations, this expert consensus reviews the definition, injury classification, rehabilitation assessment, rehabilitation strategies and rehabilitation measures of TSCI so as to provide early standardized rehabilitation treatment methods for TSCI.

OBJECTIVETo identify potential mutation in a Chinese family affected with Charcot-Marie-Tooth disease(CMT).

METHODSClinical data of the family was collected, and genomic DNA was extracted from peripheral blood samples of the family members. Seventy-two candidate genes of the proband were captured and sequenced by targeted next-generation sequencing, and the results were confirmed by Sanger sequencing. The protein structure was predicted with PyMOL-1 software.

RESULTSA homozygous missense mutation c.1894G>A(p.E632K) was identified in the exon 11 of the SH3TC2 gene in the proband. Heterozygous c.1894G>A mutation was also detected in the proband's father, mother and daughter, but not in the healthy family members and 300 normal controls. Retrieval of the NCBI, HGMD and 1000 genome databases has verified the c.1894G>A to be as a novel mutation. Computer simulation has suggested that the mutation has altered the 3D structure of the SH3TC2 protein.

CONCLUSIONThe proband was diagnosed as CMT4C, for which the underlying gene was SH3TC2. This finding has expanded the spectrum of SH3TC2 mutation in association with CMT4C.

Adult ; Aged ; Base Sequence ; Charcot-Marie-Tooth Disease ; genetics ; DNA Mutational Analysis ; Exons ; Female ; Heterozygote ; Humans ; Male ; Middle Aged ; Models, Molecular ; Molecular Sequence Data ; Mutation, Missense ; Pedigree ; Proteins ; genetics ; Young Adult

Objective The cytotoxic microbial strains isolated from the deep ocean water and sediments were screened,and the secondary metabolites of bioactive fungus c2b were investi- gated.Methods Active bioactive microbial strains were screened using brine shrimp and chro- nic medulla leucocythemia leukocythemia(K562)cell line.The cytotoxic components of fun- gus c2b were isolated by bioassay-guided fractionation and solvent extraction,silica gel col- umn chromatography and preparative HPLC.Their structures were established by pbysico- chemical properties and spectral analyses.The cytotoxicities of compounds were evaluated by SRB method.Results and Conclusion Twenty-nine strains of fungi were isolated.Among them,seven strains showed cytotoxic activities.Six compounds(1～6)were isolated and i- dentified as N-acetyl histamine(1),chrysogine(2),ergosterol peroxide(3),5,8-epidioxy- 24-methylcholesta-6,22-dien-3?-ol(4)cerevisterol(5)and(4E,8E)-N-[(2'R,3'E)-2'-hy- droxy-3'-hexadecenoyl]-1-O-?-D-glycopyranosyl-9-methyl-4,8-sphingadiene(6),respective- ly.Compound 3 and 4 showed median cytotoxicity.